FR2585018A1 - POLY-4-AMINOPYRROLE-2-CARBOXAMIDES AND DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR THERAPEUTIC USES - Google Patents

Abstract

COMPOUNDS RESPONDING TO GENERAL FORMULA I: (CF DRAWING IN BOPI) IN WHICH N IS EQUAL TO 0 OR TO A NUMBER OF 1 TO 4; R REPRESENTS A FREE AMINO GROUP, OR WITH ONE OR TWO DEFINED SUBSTITUTES, OR A -NO OR -NH-CHO GROUP, EACH OF THE SYMBOLS R REPRESENTS A HYDROGEN ATOM OR AN ALKYL GROUP IN CC AND R REPRESENTS A CC ALKYL GROUP TERMINATED BY A BASIC OR ACIDIC PATTERN OR BY A FREE HYDROXY OR GLUCOSYL GROUP, SUBJECT TO CERTAIN RESTRICTIONS, HAVE ANTIVIRAL AND ANTITUMOR PROPERTIES THAT CAN BE USED THERAPEUTICALLY. SOME OF THESE COMPOUNDS ARE NEW; THEY ARE PREPARED BY VARIOUS METHODS DESCRIBED IN DETAIL.

Description

The present invention relates to poly-4-amino

  pyrrole-2-carboxamides and derivatives, to a process for their preparation

  and pharmaceutical compositions containing these compounds.

  Distamycin A is a well-known compound having the formula:

HOC -H

2 NH2

NH-CH2-CH2-C NH

  CH3 For example, a talk on distamycin A

in Nature 203, 1064 (1964).

  The invention firstly relates to derivatives of distamycin A corresponding to the following general formula (I):

R H

NOT

R1 1I $ C-N-R

iR1 2

R1 0

  where n is 0 or a number from 1 to 4; R represents a) NHR3, R3 representing: a ') -CON (NO) R4, R4 being itself an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') CO (CH 2) m -R 5, where R 5 itself represents halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or α-unsaturated alicyclic lactone residue, and m is 0 or represents a number of I to 4;

R

  XR6 b) -N, R6 and R7 being identical and each representing R7 is an oxirane-methyl, aziridine-methyl or C2-C4 alkyl group substituted in the 2-position by a halogen or by a -OSO2R8 group, wherein R8 represents a group C 1 -C 4 alkyl or phenyl, or one of R 6 and R 7 represents hydrogen and the other has one of the meanings just given; c) -NO2; d) -NH2; or e) -NH-CHO; each of the symbols R 1 represents, independently of the others, a hydrogen atom or a C 1 -C 4 alkyl group;

  R2 represents a C1-C6 alkyl group bearing in terminal position

  a basic or acidic unit or a free hydroxy group or gluco-

  sylé, with the following restrictions: (i) R does not have the meanings given above or (a) and (b) when n is 1 and, simultaneously, R2 represents NH

-CH2-CH2-C

NH

  (ii) R can not represent -NO2 or -NH2 nor -NH-CHO when R2 NH is -alk-C, in which alk is NR'R "

  C1-C6 alkyl group and each of the symbols R 'and R "represents

  independently of the other, a hydrogen atom or a methyl group, or when n is 0 or 1, R2 / CH3 is - (CH2) p -N, where p is equal to

CH3

  at 2 or 3; and (iii) R can not represent -NH 2 when, simultaneously, n is 0 or 1, each of the symbols R 1 represents a group

  methyl and R2 is -CH2-CH2-COOH.

  The invention also includes the pharmaceutically acceptable salts of the compounds of formula (I), taking into account the above limitations, as well as any possible isomers falling within the scope of formula (CI), alone or in combination with state

mixtures.

  The invention secondly comprises pharmaceutical compositions comprising a carrier and / or diluent acceptable for pharmaceutical use and, as an active substance, a compound of formula (IA) below:

R H

p <% N NH

! 0 L G -N-R_ (IA)

R1 O I 2

R 0

  wherein n is 0 or a number of 1 to 4; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, R4 represents an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') -CO (CH 2) m -R 5, where R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or α-5-unsaturated alkenyl residue and m is 0 or a number from 1 to 4; Where R6 b) -N, R6 and R7 are identical and each RR7 is an oxiran-methyl, aziridine-methyl group or a C2-C4 alkyl group substituted in the 2-position by a halogen or -OS0 2R8 group, wherein R8 represents a C1-C4 alkyl or phenyl group,

  or one of the symbols R6 and R7 represents hydro-

  gene and the other has one of the meanings just given; c) -NO2; d) -NH2; or e) -NH-CHO; each of the symbols R1 represents, independently of the others, a hydrogen atom or a C4-C4 alkyl group; R2 represents a C1-C6 alkyl group terminating in a basic or acidic unit or a free or glucosylated hydroxy group, with the following restrictions: (i) R can not have the meanings given above under a) and b) when n is equal to 1 and that simultaneously R2 represents

NH2

  -CH2CH2-C; and NH2 (iv) R can represent neither -NO2 nor -NH2 nor -NHCHO when R2NH is -alk-C, wherein alk is

NNR 'R "

  a C1-C6 alkyl group and each of the symbols R 'and R "represents, independently of the other, a hydrogen atom

or a methyl group. -

  The invention also comprises, in its second object, the pharmaceutical compositions containing, as an active substance, a salt acceptable for the pharmaceutical use of a compound of formula (IA), taking into account the restrictions mentioned above, as well as any possible isomer or mixture of isomers

the frame of the formula (IA).

  With reference to both formulas (I) and (IA) above, the preferred meanings for the various symbols are as follows: when R4 is unsubstituted C1-C4 alkyl, it is preferably a group methyl or ethyl, especially methyl; when R4 is a C1-C4 alkyl group substituted by halogen, the halogen is preferably chlorine or bromine; in such a case, the preferred meanings for R4 are chloroethyl and fluoroethyl; the preferred values for n are 0, 1 and 2; when R5 is halogen, it is preferably chlorine or bromine; when R5 represents a radical of ketone or alicyclic lactone a, unsaturated, it is for example a group __ 0 or

0

  respectively of a group 0; the preferred meanings for R5 are oxiranyl (/ ..); 1-aziridinyl (); cyclopropyl (- C3); a group - <or a group 0; the preferred meanings for m are 0, 1 or 2; C2-C4alkyl substituted at the 2-position with halogen, as represented by R6 / R7 is preferably 2-chloroethyl; a C2-C4 alkyl group substituted in the 2-position by a -OSO2R8 group, as represented by R6 / R7 is preferably a -CH2-CH2-OS02R8 group, wherein R8 is a C1-C4 alkyl group, preferably a methyl group; preferably, each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group, more especially methyl, and under the best conditions all the R 1 symbols represent methyl groups; account is taken of the restrictions made above, when R 2 represents a C 1 -C 6 alkyl group terminated with a basic unit, the C 1 -C 6 alkyl group is preferably a C 1 -C 4 alkyl group, in particular ethyl or n-propyl; and the basic unit is, for example, an amino group; a mono- or di-C 1 -C 6 alkylamino group, for example di (C 1 -C 4) alkylamino; an amidino group, a group /, CH3-N = N-N; or a nitrogen-containing heterocycle, for example CH 3 an imidazolyl, imidazolinyl, tetrahydropyrimidinyl or oxazolidinyl ring. These particular heterocycles are those which are preferred whenever a nitrogen-containing heterocycle is mentioned in the present application; Preferred C1-C6 alkyl groups ending in a basic unit, among those represented by R2, are, for example, taken into account the above restrictions: ## STR2 ## - - (CH 2) pC (CH 3 CN 3 '- (CH 2) pC,

CH3 NH2

  ## STR1 ## ## STR2 ## and ## STR2 ##

P N _ // 0 / J NCH3

H H

  in which p is a number from 1 to 4; when R2 represents a C1-C6 alkyl group terminating in an acid unit, the C1-C6 alkyl group is preferably a C1-C4 alkyl group, in particular an ethyl or n-propyl group, and the acid unit is preferably a carboxy group; among the C1-C6 alkyl groups ending in an acidic unit represented by R2, for example, a group - (CH2) p-COOH in which p is a number from 1 to 4; when R2 represents a C1-C6 alkyl group terminating in a free hydroxy group, it is, for example, a - (CH2) p -CH2OH group in which p is a number from 1 to 4; when R2 represents a C1-C6 alkyl group terminated by a hydroxy glucosyl group, it is for example a group

  - (CH2) p-CH2-O-D in which p has the meanings indicated below

  above and D is a residue of sugar or an amino sugar.

  The sugar residue may be for example a glucose, mannose or ribose residue; the amino-sugar residue may be for example a daunosamine residue which may optionally

  salified, for example with acetic acid, trifluorinated

  acetic acid, or hydrochloric acid.

  Among the pharmaceutically acceptable salts of the compounds of Formula (I) and (IA), there will be mentioned the acid salts acceptable for pharmaceutical use, as well as mineral acids such as, for example, hydrochloric acid, hydrobromic acid, nitric acid and sulfuric acid, than organic acids such as, for example, acetic acid, trifluoroacetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, methanesulphonic acid, ethanesulphonic acid, but they are also basesacceptables salts for pharmaceutical use, both mineral such as for example alkali metal hydroxides such as sodium hydroxide or potassium hydroxide , or alkaline earth metals, for example calcium or magnesium, or zinc or aluminum, than organic bases such as for example aliphatic amines such as methylamine,

  diethylamine, trimethylamine, ethylamine and heteroamines.

  cyclic such as piperidine.

  The salts of the compounds of formula (I) or (IA) and of acids may be, for example, the salts of compounds of formula (I) or (IA) in which R 2 is a C 1 -C 6 alkyl group ending in

  a basic pattern, and an acid such as those mentioned above.

  The salts of the compounds of formula (I) or (IA) and of bases may be, for example, the salts of the compounds of formula (I) or (IA) in which R 2 represents a C 1 -C 6 alkyl group ending in an acidic unit , and a base, for example one

of those mentioned above.

  A particular class of compounds of formula (I) according to the invention (hereinafter referred to as class A) consists of the compounds of formula (I) in which, taking into account the restriction mentioned above under (i) n is 0 or represents a number from 1 to 4; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, R4 represents an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') -CO (CH 2) m -R 5, wherein R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or alicyclic lactone residue which is unsaturated, and m is 0 or a number from 1 to 4; or "R6 b) -N, R6 and R7 being identical and representative

R7

  each is an oxiran-methyl, aziridin-methyl group or a C2-C4 alkyl group substituted in the 2-position by a halogen or -OSO2R8 group, wherein R8 is a C1-C4 alkyl or phenyl group;

  or one of the symbols R6 and R7 represents hydro-

  gene and the other has one of the meanings just given;

  each of the symbols R1 represents, independently, a hydrogen atom

  gene or a C1-C4 alkyl group; R2 represents a C1-C6 alkyl group terminating in a basic or acidic unit or a free or glycosylated hydroxy group;

  and their pharmaceutically acceptable salts.

  The preferred meanings for the various substitutes

  of this class are the same as those listed above

  in the present application with reference to formulas (I) and (IA).

  A preferred group of compounds in this class A consists of the compounds of formula (I) wherein, given the restriction given under (i) above, n is 0, 1 or 2; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, R4 being itself a C1-C4 alkyl group substituted by a halogen, or b') -CO (CH2) m-R5, R5 representing a halogen, an oxiranyl, 1-aziridinyl, cyclopropyl or a non-unsaturated alicyclic lactone residue and m is 0, 1 or 2; or R 6 b) -N, R 6 and R 7 being identical and R7 representative

  each an oxirane-methyl group, 1-aziridine-

  methyl or a C 2 -C 4 alkyl group substituted in the 2-position by a halogen or -OSO 2 R 8 group, wherein R 8 is a C 1 -C 4 alkyl group; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic unit, and their acid salts acceptable for pharmaceutical use, in

  particularly hydrochloric acid.

  In the preferred group of compounds discussed above, a C 1 -C 4 alkyl group represented by R 4

  is preferably a methyl or ethyl group; a halogen atom

  gene is preferably a chlorine atom; a residue of lactone

  c, β-unsaturated cyclic is preferably a group / 0 0; C2-C4alkyl in R6 / R7 is preferably ethyl; when R6 and R7 are C2-C4 alkyl groups substituted in the 2-position by halogen, it is preferably 2-chloroethyl groups; when R6 and R7 are C2-C4 alkyl groups substituted at the 2-position by a -OS02R8 group wherein R8 is C1-C4 alkyl, it is preferably methanesulfonyloxyethyl groups; a C1-C4 alkyl group represented by R1 is preferably a methyl group; in the substituent R 2, the C 1 -C 6 alkyl group is preferably a C 1 -C 4 alkyl group, more especially ethyl or n-propyl, and the basic terminal unit is preferably an amino group; mono- or di- (C1-C6) alkylamino; amidino; / CH3 a group -N = N-N; or a heterocycle containing nitrogen; CH3 the most preferred meanings for R2 are those given above, especially - (CH2) p -N and - (CH2) -C in

CH3 NH2

  which p is a number from 1 to 4, more particularly 2 or 3.

  Particular examples of preferred compounds of Class A above include the following:

  9-EN-methyl-4- [N-methyl-4- (3-methyl-3-nitrosoureido) pyrrole-2

  carboxamido] pyrrole-2-carboxamido) propionamidine; 0-EN-methyl-4-EN-methyl-E3- (2-chloroethyl) -3-nitrosoureido] pyrrole-2-carboxamido) pyrrole-2-carboxamido) propionamidine;

  3-IN-methyl-4-EN-methyl-4-E3-methyl-3-nitrosoureido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-E3- (2-chloroethyl) -3-nitrosoureido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyLdiméthylamine;

  3-IN-methyl-4-EN-methyl-4- [N-methyl-4- (3-methyl-3-nitrosoureido) -

  pyrrole-2-carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4- [3- (2-chloroethyl) -3-nitro-

  souréido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

carboxamido] propyldiméthylamine;

  N-deformyl-N-EN-methyl-4- (3-methyl-3-nitrosoureido) pyrrole-2

carboxamido] distamycin A;

  N-deformyl-N-EN-methyl-4-E3- (2-chloroethyl) -3-nitrosoureido] -

  pyrrole-2-carboxamidoldistamycin A;

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4 (3-methyl-3-

  nitrosoureido) pyrrole-2-carboxamido] pyrrole-2-carboxamidoJpyrroLe-

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4-U3- (2-chloro-

  ethyl) -3-nitrosoureido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyLdiméthylamine;

  f- [N-methyl-4-EN-methyl-4- (oxirannecarboxamido) pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] propionamidine;

  3- [N-methyl-4- [N-methyl-4- (oxirannecarboxamido) pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4-oxirannecarboxamido) pyrrole

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

dimethylamine;

  N-deformyl-N- [N-methyl-4- (oxirannecarboxamido) pyrrole-2-carboxamide

mido] distamycin A;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- (oxiranne-

  carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

   - [N-methyl-4- [N-methyl-4- (cyclopropylcarboxamido) pyrrole-2

  carboxamido] pyrrole-2-carboxamido] propionamidine;

  3- [N-methyl-4-EN-methyl-4- (cyclopropylcarboxamido) pyrrole-2

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4- [N-methyl-4- (cyclopropylcarboxamido) -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  N-deformyl-N- [N-methyl-4- (cyclopropylcarboxamido) pyrrole-2

carboxamido] distamycin A;

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4- (cyclopropyl-

  carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  e- [N-methyl-4- [N-methyl-4- (3-méthyLoxirannecarboxamido) pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propionamidine;

  3- [N-methyl-4-EN-methyl-4- (3-méthyloxirannecarboxamido) pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4- [N-methyl-4- (3-méthyloxirannecarboxamido) -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  N-deformyl-N-EN-methyl-4- (3-méthyloxirannecarboxamido) pyrrole-2-

carboxamido] distamycin A;

  3-IN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4- (3-méthyloxiran-

  necarboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4- (2-chloroéthylcarboxamido) pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propionamidine;

  3- [N -methyl-4-EN-methyl-4- (2-chloroéthylcarboxamido) pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4-CN-methyl-4-EN-methyl-4- (2-chloroéthylcarboxamido) -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  N-deformyl-N-EN-methyl-4- (2-chloroéthylcarboxamido) pyrrole-2-

carboxamido] distamycin A;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- (2-chloroethyl

  carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido) pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  0- [N-methyl-4-EN-methyl-4-E1- (aziridine) carboxamido) pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propionamidine;

  3-IN-methyl-4-EN-methyl-4-E1-aziridine) carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-E1- (aziridine) carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  N-deformyl-N-EN-methyl-4-E1- (aziridine) carboxamido] pyrrole-2-

carboxamido] distamycin A;

  3-IN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4- [1- (aziridine) -

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  1- [N-methyl-4-EN-methyl-4- [N, N-bis (2-chloroethylamino)] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propionamidine;

  3- [N-methyl-4-EN-methyl-4- [N, N-bis (2-chloroethylamino)] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4- [N-methyl-4-EN-methyl-4-EN, N-bis (2-chloroethylamino)] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  N-deformyl-N- [N-methyl-4- [N, N-bis (2-chloroethylamino)] pyrrole-2-

carboxamido] distamycin A;

  3-IN-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4- [N, N-bis (2-

  chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine; and their pharmaceutically acceptable salts, especially

hydrochlorides.

  Another particular class of compounds of formula (I) according to the invention (hereinafter referred to as class B) consists of the compounds of formula (I) in which, taking into account the restrictions given above under (ii) and (iii), n is 0 or a number of 1 to 4; R is -NO2; -NH 2 or NHCHO; each of the symbols R 1 represents, independently of the others, hydrogen or a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group with a basic terminal or acidic unit or terminated with a free or glucosylated hydroxy group, and

  their acceptable salts for pharmaceutical use.

  In this class, the preferred meanings for the various symbols are those given above in

  reference to formulas (I) and (IA).

  A preferred group of compounds in class B consists of the compounds of formula (I) in which, taking into account the restrictions given under (ii) and (iii) above, n is equal to 0 or represents a number from 1 to 4; R is -NO2; -NH2 or -NHCHO; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 is a C1-C6 alkyl group terminated with a substituent selected from the group consisting of: amino; mono- and di- (C 1 -C 6 -alkyl) amino; a group -N = N-N c; a heterocycle containing CH3 nitrogen; COOH; -CH2-OH; and -CH 2 -O-D, D being the residue of a sugar or an amino sugar,

  and their pharmaceutically acceptable salts.

  In the preferred group of above compounds, a C1-C4 alkyl group represented by R1 is preferably a methyl group and the C1-C6 alkyl group of R2 is preferably

  a C1-C4 alkyl group, more especially ethyl or n-propyl.

  Most preferred R2 groups are: - (CH2) -N CH; - (CH2) p-C; - (CH2) p-C; - (CH2) p-C \);

H H H

  p N; (CH2) PC \; - (CH2) P-COOH; - (CH 2) p -CH 2 OH and - (CH 2) p-CH 2 O -D wherein p is a number from 1 to 4, more especially 2 or 3, and D having

  the meaning indicated above.

  Examples of particular compounds of Class B above are: 3-EN-methyl-4- [N-methyl-4-EN-methyl-4-ENmethyl-4-nitropyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

carboxamido] propyldiméthylamine;

  3-IN-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4-

  nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyLamine;

  3-IN-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4-

  EN-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-aminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

carboxamido] propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-

  aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propytdiméthylamine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-

  EN-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-carboxamidoj-

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-

  formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldi-

methylamine;

  3-IN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4-

  EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4- [N-methyl- (4-formylamino) pyrrole-2

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamidoléthyl-

[2-imidazole];

  1-EN-methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (2-imidazoline)];

  f-EN-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl-

  [2- (3,4,5,6-tetrahydropyrimidine)];

  0-IN-methyl-4- [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl-

[2- (4,5-dihydro) oxazole];

  3-EN-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-2- acid

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionic acid;

  alcohol 5-EN-methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl;

* 3-EN-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propane

  1-E [(3-amino-2,3,6-trideoxy-a-L-lyxo-hexapyrannosyl) oxy] trifluoro-

  acetate; and, where applicable, their acceptable salts for use

  pharmaceutical, especially hydrochlorides.

  The invention also comprises a process for preparing a compound of formula (I), which process comprises: (A) reacting a compound of formula (II)

- (II)

H21 CONH- R2

  R1 wherein R1 and R2 have the meanings given above, but restriction (iii) does not apply, and q is a number from 1 to 5, with a compound of formula (III): O2N z R1 (III) in which R1 has the indicated meanings Z is an eliminable group, the reaction giving formula (I) wherein R represents -NO2; or (B) the reduction of a compound of formula (IV): above and a compound of O2N wherein n. R1 and R2 have the meanings given above, with the restriction that n can not represent 0 or 1 When each of the symbols R1 represents a methyl group and R2 represents -CH-CH-COOH, the reaction giving a compound of formula ( I) wherein R represents - NH2; or (C) Formylation of a compound of formula (V): ## STR2 ##

R R

R1 0

  wherein n, R 1 and R 2 have the meanings indicated above, but restriction (iii) does not apply, to give a compound of formula (I) wherein R is -NH-CHO; or (IV) (D) reacting a compound of formula (V) wherein R1, R2 and n have the meanings indicated above, with a compound of formula (VI):

Z'-C-N (NO) -R4 (VI)

  wherein R4 has the meanings indicated above and Z 'represents a leaving group, to give a compound of formula (I) wherein R represents -NHR3 and R3 represents -CON (NO) R4, R4 having the meanings indicated ci -above; or (E) reacting a compound of formula (V) wherein R 1, R 2 and n have the meanings indicated above, with a compound of formula (VII): Z-CO- (CH 2) m -R 5 ( VII) wherein R5, m and Z have the meanings given above, to give a compound of formula (I) wherein R represents -NHR3 and R3 represents -CO (CH2) m-R5, m and R5 having as indicated above, or (F) the reaction of a compound of formula (V) wherein R1, R2 and n have the meanings indicated above, with a compound of formula (VIII):

X-CH-CH

\ / 2 C (VIII)

  wherein X may be hydrogen, C1-C2alkyl or halomethyl to give a compound of formula (IX): wherein R1, R2 and n have the meanings given above and each symbols X has the meaning corresponding to that

  symbol X of the formula (VIII), followed by

  forming a compound of formula (IX) into a compound of formula (I)

R

  R6 wherein R is -N, R6 and R7 having the meanings R7 indicated above; after which, if desired, the substituent R2 is modified in a compound of formula (I) above, subject or not subject to the restrictions indicated above, so as to obtain a compound of formula (I) in which the substituent R2 is different, and / or is desired, a compound of formula (I) is salified or a free compound is obtained from a salt and / or, if desired, a mixture of isomers of formula (I) in

the individual isomers.

  The eliminable group Z of the compounds (III) and (VII) may consist for example of a halogen atom such as chlorine

  or bromine, or an imidazolyl or phenoxy group.

  The leaving group Z 'of the compounds (VI) may consist for example of an azido or trichlorophenoxy or succinimido-N-oxy group. The reaction between a compound of formula (II) and a compound of formula (III) is preferably carried out in the presence of a solvent and also, preferably, with an excess of the compound of formula (III), for example with about 1 , 1 to 2 moles of

  compound (III) for 1 mole of the compound (II).

  The solvent is preferably an inert organic solvent selected from dialkyl sulfoxides, such as dimethyl sulfoxide,

  dialkylamides of aliphatic acids, for example dimethyl

  formamide, heterocyclic amines such as pyridine, aliphatic alcohols and also water. Dimethylformamide is a particularly preferred solvent. The reaction temperature can range from about -50 ° C. to + 50 ° C. The time required for the reaction can

  vary within the approximate range of 0.5 to 24 hours.

  The reduction of a compound of formula (IV) can be carried out for example by catalytic hydrogenation according to known procedures, for example using palladium on charcoal,

  platinum, rhodium or Raney nickel as a catalyst.

  The reduction can be carried out for example at room temperature and at atmospheric pressure in an inert solvent, for example ethanol, methanol or dimethylformamide, in the presence of

palladium 10% on charcoal.

  The formylation of a compound of formula (V) can be carried out for example with the mixed anhydride of formic acid and acetic acid, optionally in the presence of an amine

  such as pyridine, triethylamine or dimethyl-

  aniline, as described for example in British Patent No. 1,061,639; or with N-formylimidazole obtained from carbonylimidazole and formic acid as described for example in J. Org. Chem. (1985) 50 3774-3779; or using formamide

  and ethyl formate as described for example in Gazz. Chim.

Ital. 99, 632 (1967).

  The reaction between a compound of formula (V) and a compound of formula (VI) is preferably carried out in the presence of a solvent and also, preferably, with an excess of the compound of formula (VI), for example with about 1 1 to 2 moles of the compound (VI) per mole of the compound (V). The solvent is preferably

  an inert organic solvent chosen, for example, from dialkyl

  sulfoxides such as dimethylsulfoxide, aliphatic acid dialkylamides such as dimethylformamide or dimethylacetamide, phosphoric acid triamide or hexamethylphosphoramide or

  again, for example, dioxane or dimethoxyethane. Dimethyl

  formamide (DMF) is the most preferred solvent. The reaction temperature can range from about -10 to about 25 ° C; the temperature of 0 C

is particularly appreciated.

  The time required for the reaction may vary

  in the range of about 0.5 to 6 hours.

  Similarly, the reaction between a compound of formula (V) and a compound of formula (VII) is preferably carried out in the presence of a solvent and also, preferably, with the aid of an excess of the compound of formula ( VII), for example with about 1.1 to 2 moles of the compound (VII) per mole of the compound (V). The solvent is preferably an inert organic solvent selected from dialkyl sulfoxides such as dimethyl sulfoxide, dialkylamides of aliphatic acids such as dimethylformamide, heterocyclic amines such as pyridine, aliphatic alcohols and also water.

  DMF is particularly preferred as a solvent.

  The reaction temperature may range from about -50 to +50 C. The time required for the reaction may vary in

  the approximate interval from 0.5 to 24 hours.

  When, in the compound of formula (VIII), X represents a halomethyl group, it is preferably a group

chloromethyl or bromomethyl.

  The reaction between a compound of formula (V) and a compound of formula (VIII) is preferably carried out in the presence of a solvent and also, preferably, with an excess of the compound of formula (VIII), for example about 25 to 50 moles of the compound (VIII) per mole of the compound (V). The solvent may consist for example of water, an aliphatic alcohol such as methanol or ethanol, an aliphatic carboxylic acid such as the acid

  acetic acid, a dialkylamide of aliphatic acid such as dimethyl

  formamide, or a dialkyl sulfoxide such as dimethyl sulfoxide, dioxane or dimethoxyethane. Methanol is a solvent

particularly appreciated.

  The reaction temperature can range from -20 to +25 C

about.

  The time required for the reaction may vary

  the approximate range of 2 to 48 hours.

  Transformation of a compound of formula (IX) into an R6 compound of formula (I) wherein R represents the group -N R? in which R6 and R7 have the meanings indicated above, can be carried out by common reactions in organic chemistry. Thus, for example, a compound of formula (IX) in which each of the symbols X is hydrogen or a C1-C2 alkyl group can be reacted with a halogenating agent such as, for example, a halogen such as chlorine or chlorine. bromine or a thionyl halide such as thionyl chloride to give a compound of formula (I) wherein R is -N, wherein each of R6 and R7 represents a C2-C4 alkyl group substituted with position 2 by a halogen

such as chlorine or bromine.

  Similarly, a compound of formula (IX) in which X is hydrogen or a C 1 -C 2 alkyl group can be reacted with a sulfonic acid of formula R 8 SO 3 H, wherein R 8 has the meanings indicated above or else more preferably, with a reactive derivative of such an acid, for example a corresponding sulfonyl halide such as chloride, or an anhydride; there is obtained a compound R6 of formula (I) wherein R represents a group -N R7 wherein each of R6 and R7 represents a C2-C4 alkyl group substituted in the 2-position by a -O-SO2R8 group,

  wherein R8 has the meanings given above.

  On the other hand, a compound of formula (IX) in which each of the symbols X represents a halomethyl group, for example chloromethyl or bromomethyl, can be reacted with a base to give a compound of formula (I) wherein R6 R represents a group -N, in which each of the symbols R6

  and R7 represents an oxirane-methyl group.

  The base may consist either of a mineral base such as, for example, an alkali metal hydroxide, for example sodium or potassium hydroxide or an alkaline earth metal hydroxide, for example calcium or magnesium, or an organic base such as that for example an aliphatic amine such as trimethylamine or a heterocyclic amine such as pyridine, piperidine,

morpholine or methylmorpholine.

  Other compounds of formula (I) wherein R / R6 is -N may be prepared from an R7 compound of formula (IX) by well known reactions in chemistry.

  organic and according to known procedures.

  The modifications of the group R2. a compound of formula (I) subject or not to the restrictions indicated above,

  in order to obtain a compound of formula (I) in which the substitute

  killing R2 is different, can be done according to different modes

known operating procedures.

  Among these modifications, there will be mentioned for example: (a ') in a substituent R2 consisting of a C 1 -C 6 alkyl group terminated with an amidino group (-C), the NH 2 amidino group is converted into a heterocycle, for example a cycle

N N

  2-imidazole (t 3 or 2-imidazoline or in one

N N

I I

H H

  carboxy group; (b ') in a C1-C6 alkyl substituent terminating in -COOH, the -COOH group may be converted to the -CH2OH group; and (c ') in a substituent R2 being a C1-C6 alkyl group terminated with a free hydroxy group, the

  free hydroxy group to a glucosylated hydroxy group.

  With regard to the modifications mentioned above under (a '), the conversion of the amidino group to the 2-imidazole ring can be carried out for example by reaction with dimethylacetal aminoacetaldehyde according to a known procedure, while for example, ethylenediamine can be used to convert the amidino group to a 2-imidazoline ring; the conversion to other heterocycles can be carried out in the same way by

known methods.

  Basic hydrolysis, for example with sodium hydroxide in methanol at the reflux temperature, may be used, for example, to convert the amidino group to a carboxy group. The conversion of the carboxy group into a -CH 2 OH group referred to in (b ') above can be carried out for example by reduction according to a conventional procedure, by

  example using NaBH4 as reducing agent.

  Conventional etherification procedures can be observed to convert the free hydroxy group into a

  glucosylated hydroxy group as mentioned in (c ') above.

  Naturally, the various modifications of the

  The above-mentioned R2 radicals can be carried out in the absence of interfering groups on the rest of the molecule of formula (I). Otherwise, you must first protect the existing annoying groups and then reintroduce them, in your usual way, after

the modification on R2.

  Salification of a compound of formula (I) and the preparation of a free compound from a salt can be

  performed according to known procedures.

  Conventional procedures, such as fractional crystallization and chromatography, can also be used to separate a mixture when desired.

  isomers of formula (I) to the individual isomers.

  The compounds of formula (II) can be obtained by known procedures, for example those described for

  the preparation of derivatives of distamycin in Gazz. Chim.

Ital. 97, 1110 (1967).

  For example, in particular, it is possible to obtain a compound of formula (II) in which q is equal to 1 by reducing a compound of formula (X): O 2 N -O

N CONH-R (X)

R1

  wherein R1 and R2 have the meanings given above.

  It is possible to obtain a compound of formula (II) in which q is equal to 2 by reacting a compound of formula (II) in which q is equal to I with a compound of formula (III) above, which gives a compound of formula (XI): ## STR5 ##

R. CONH-R

1 R1

  in which R1 and R2 have the meanings indicated above,

  which is itself subject to reduction.

  Similarly, by subjecting a compound of formula (II) wherein q is 2 or 3 or 4, to the same reaction as above with a compound (III) followed by reduction, a corresponding compound of formula (II)

  wherein q is 3, 4 or 5, respectively.

  The reduction of nitro derivatives, for example compounds (X) and (XI) above, can be carried out as indicated

  higher for the reduction of compounds (IV).

  The conditions of the reaction between the compounds (II)

  and the compounds (III) have already been described above.

  The compounds of formula (III) are known or can

  be prepared by known methods from known compounds.

  The compounds of formula (IV) can be obtained by

  reaction between the compounds (II) and the compounds (III).

  The compounds of formula (V) can be obtained by

reduction of compounds (IV).

  The compounds of formula (VI) are known and can be prepared for example as described in J. Med. Chem. (1982)

, 178-182.

  The compounds of formula (VII) and (VIII) are also known or can be prepared by known methods from known compounds. In particular, for example, the compounds of formula (VII) are commercially available or can be prepared by activation of related carboxyl derivatives, in a

classical surgery.

  Compounds (VIII) are generally commercially available. The compounds of formula (X) can be obtained by reacting a compound of formula (III) with a compound of formula (XII)

R2-NH2 (XII)

  in which R2 has the meanings indicated above, according to for example the usual conditions described in organic chemistry

for the acylation of amines.

  The compounds of formula (XII) are known or exist

in the trade.

  As already mentioned, the subject of the invention is also pharmaceutical compositions containing a compound

  of formula (IA) above as an active substance.

  A particular class of compositions according to the invention

  (hereinafter referred to as class C) consists of pharmaceutical compositions comprising a carrier and / or diluent acceptable for pharmaceutical use and, as an active substance, a compound of formula (IA) above in which , taking into account the restriction mentioned above under (i), n is equal to 0 or represents a number from 1 to 4; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, R4 represents an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') -CO (CH 2) m -R 5, wherein R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or alicyclic α, 5-unsaturated lactone and m is 0 or a number from 1 to 4; or "R6 b) -N, R6 and R7 being identical and representative

R7

  each is an oxiran-methyl, aziridin-methyl or C2-C4 alkyl group substituted in the 2-position by a halogen or by a group -OSO2R8 in which R8 represents a C1-C4 alkyl or phenyl group, or else one of the symbols R6 and R7 represent hydrogen and the other has one of the meanings just given; each of the symbols R 1 represents, independently of the others, hydrogen or a C 1 -C 4 alkyl group; R2 represents a C1-C6alkyl group terminated with a basic or acidic unit or with a free or glucosylated hydroxy group,

  or a salt acceptable for the pharmaceutical use of such a compound.

  In this class, the preferred meanings for the various symbols are the same as those indicated above

  with reference to formulas (I) and (IA).

  A preferred group of compounds of formula (IA) in the context of class C above are compounds of formula (IA) in which, taking into account the restriction mentioned

above under (i), -

  is not equal to 0, 1 or 2; R represents a) -NHR3, R3 represents: a ') CON (NO) R4, where R4 is a C1-C4 alkyl group substituted with halogen, or b) -CO (CH2) mR, where R5 represents a halogen, a oxiranyl, 1-aziridinyl, cyclopropyl or a monounsaturated alicyclic lactone residue, and m is 0, 1 or 2; or else / R6 b) -N, R6 and R7 being identical and representative

R

  each an oxirane-methyl group, 1-aziridine-

  methyl or C2-C4alkyl substituted in the 2-position by halogen or -OSO2R8, wherein R8 is C1-C4alkyl; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic unit, and their acid salts acceptable for pharmaceutical use,

  in particular hydrochloric acid.

  In the preferred group of compounds discussed above, a C 1 -C 4 alkyl group represented by R 4

  is preferably a methyl or ethyl group; a halogen atom

  gene is preferably a chlorine atom; an α, O-unsaturated alicyclic lactone residue is preferably a group / 0; a C2-C4 alkyl group represented by R6 / R7 is preferably an ethyl group; when R6 and R7 are C2-C4 alkyl groups substituted at the 2-position by halogen, it is preferably 2-chloroethyl groups; when R6 and R7 are C2-C4 alkyl groups substituted at the 2-position by a -OSO2R8 group in which R8 is an alkyl group

  C1-C4, it is preferably methanesulphonyloxy-

  ethyl; a C1-C4 alkyl group represented by R1 is preferably a methyl group; in the substituent R 2, the C 1 -C 6 alkyl group is preferably a C 1 -C 4 alkyl group, more especially ethyl or n-propyl, and the terminal basic unit is preferably an amino group; mono- or di- (C1-C6) alkylamino; amidino; CH3 a group -N = N-N; or a heterocycle containing nitrogen;

CH3

  the most popular meanings for R2 are those that have

/ CH3

  given above, in particular - (CH2) p -N and 2 p 'lC

10 NH

  and - (CH 2) p-C N in which p is a number from 1 to 4, plus NH 2

particularly 2 or 3.

  Among the particular compounds of formula (IA) most preferred in Class C above are, inter alia, those which have been mentioned above as being preferred for Class A, especially in the form of L-salts. 'hydrochloric acid. A particular class of compositions according to the invention (hereinafter class D) consists of pharmaceutical compositions comprising a carrier and / or diluent acceptable for pharmaceutical use and, as an active substance, a compound of formula (IA) ci above, in which, taking into account the restriction mentioned above under (iv), n is equal to 0 or represents a number from 1 to 4;

  R represents -NO2, -NH2 or -NH-CHO; each of the symbols R1 represents

  independently of the others, hydrogen or a C1-C4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic or acidic unit or with a free or glucosylated hydroxy group;

  or a salt acceptable for the pharmaceutical use of such a compound.

  In class D above, the preferred meanings for the various symbols are the same as those that have been

  indicated above with reference to formulas (I) and (IA).

  A preferred group of compounds of formula (I) in the context of said class D consists of compounds of formula (IA) wherein n is 0 or a number of I to 4; R represents -NO2, -NH2 or -NHCHO; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a substituent selected from the group consisting of amino groups; monoet / CH3 / 3 di (C1-C6) alkyl amino; The group -N = N-N; a heterocycle

CH3

  containing nitrogen; COOH; -CH2-OH; and -CH2-O-D, D being a residue of sugar or amino-sugar,

  and their pharmaceutically acceptable salts.

  In the preferred group of above compounds, a C1-C4 alkyl group represented by R1 is preferably a methyl group, and the C1-C6 alkyl group of the substituent R2 is preferably a C1-C4 alkyl group, preferably especially ethyl or n-propyl. Among the most preferred R 2 groups, there will be mentioned: CH (CH 2 NpCN 2) - (CH 2) p -N -CHCH 2) Np-C; - (CH2) P-C - (CH2) p-CD;

3 1 "

H H H

  Nh. - (CH 2) p-C); - (CH 2) p-COOH; - (CH2) p-CH20H and - (CH2) p-CH2-O-D; in which p is a number from 1 to 4, especially 2 or 3, and

  D has the meaning indicated above.

  As examples of particular compounds of formula (IA)

  contained as an active substance in the pharmaceutical compositions

  class D above, the following are mentioned:

  3-EN-methyl-4- (N-methyl-4-nitro-pyrrole-2-carboxamine) pyrrole-2

carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-nitropyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-nitropyrrole-

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamidolpyrrole-

2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4-

  nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyl-

amine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-

  EN-methyl-4-nitropyrrole-2-carboxamido] pyrrote-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-aminopyrrole-

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-

carboxamido] propyldiméthylamine;

  3-IN-methyl-4- [N-methyl-4-EN-methyl-4-aminopyrrole-2-carboxamido) -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyLamine;

  3- [N-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4-

  aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4-

  [N-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole

2-carboxamido] propyldiméthylamine;

  3- [N -methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4- [N-Methyl-4- [N-Methyl-4-formylaminopyrrole-

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-

  formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

dimethylamine;

  3-IN-methyl-4-EN-methyl-4- [N-méthym-4- [N-methyl-4-EN-methyl-4-

  EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  B-EN-methyl-4-EN-methyl-4-EN-methyl- (4-formylamino) pyrrole-2

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl-

[2-imidazole];

  B- [N-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrroLe-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (2-

imidazoline)];

  B- [N-methyl-4- [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl-

  [2- (3,4,5,6-tetrahydropyrimidine)];

  B-EN-methyl-4- [N-methyl-4-EN-Methyl-4-formylaminopyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (4,5-

dihydro) oxazole];

  1-EN-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrrole acid

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionic acid;

  5- [N-methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole] alcohol;

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl; 3EN-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propane-1 - [(3-

  amino-2,3,6-trideoxy-a-L-lyxo-hexapyrannosyl) oxy] trifluoroacetate

  and where applicable, their acceptable salts for pharmaceutical use.

  especially the hydrochlorides.

  The compounds of formula (IA), the active ingredient of the pharmaceutical compositions according to the invention, can be prepared by known methods, for example those described in British Patents 1,009,797 and 1,061,639, as well as by

  processes described above in this application for the preparation of

  ration of the compounds of formula (I).

  The compounds according to the invention having the formula (IA) may be useful as anti-viral agents

and anti-neoplastics.

  They have, for example, remarkable efficacy in inhibiting the reproductive activity of pathogenic viruses and

* protecting the cells of the tissues against viral infections.

  For example, they are active against DNA viruses such as, for example, herpes viruses, for example herpes simplex and herpes zoster, and adenoviruses, as well as against retroviruses such as, for example, sarcoma viruses, for example for example murine sarcoma virus and leukemia viruses, for example Friend's leukemia virus. For example, herpes viruses, coxsackies and respiratory syncytial viruses have been tested in liquid media in the following manner: Serial dilutions of two times compounds ranging from 1.5 mcg / ml, 0.1 ml / dish, with two cups per dilution, in microplates with 96 cups for culture

of tissues.

  0.1 ml / dish were immediately added to cell suspensions (2 × 10 5 cells / ml), uninfected for control of cytotoxicity, or infected with approximately 10-3 TCID 50 of virus / cells. After 3 to 5 days of incubation at 37 ° C with 5% CO 2, the cell cultures were examined under a microscope and the maximum tolerated dose (MxTD) was determined.

  Minimal Inhibitory Centering (MIC). MxTD is the maximum concentration of the compound allowing monolayer growth

  similar to that of witnesses by density and morphology.

  The MIC is the minimum concentration causing a decrease in

  cytopathic effect compared to infected controls.

  The compounds were considered active when

  their activity index calculated by the MxTD / MIC ratio was> 2.

  For example, for the compound according to the invention

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-nitropyrrole-

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] propyldimethylamine (internal code FCE 24558) in in vitro assays, an activity index of about 8 on Herpes simplex-infected Hep n 2 cells and about 4 on Hep n 2 cells was found B. For distamycin A, the same tests indicate an activity index of about 4 on herpes simplex-infected Hep n 2 cells and an index of <I activity on coxsackie-infected Hep n 2 cells. B. The compounds of formula (IA) according to the invention also have cytostatic properties with respect to tumor cells so that they can be used, for example, to inhibit the growth of various tumors such as, for example, carcinomas eg breast carcinoma, lung carcinoma, bladder carcinoma, colon carcinoma, ovarian and endometrial tumors. Other neoplasias in which the compounds according to the invention find applications include, for example, sarcomas, for example sarcomas of soft tissue and bone, and haematological malignancies, for example

leukemias.

  The compounds according to the invention can be administered by the usual routes, for example parenterally, for example by injection or intravenous infusion, intramuscularly,

  subcutaneous, topically or orally.

  The dosage depends on the age, weight and condition of the

  patient and the route of administration.

  For example, an appropriate dosage for the administration

  The treatment with adult humans can range from about 0.1 to 100 mg per dose I to 4 times daily.

  As already mentioned, the pharmaceutical compositions

  according to the invention contain a compound of formula (IA) as an active substance, in combination with one or more

  excipients acceptable for pharmaceutical use.

  The pharmaceutical compositions according to the invention are usually prepared by conventional procedures

  and are administered in a suitable pharmaceutical form.

  For example, solutions for intravenous injection or infusion may contain as vehicles for example sterile water or preferably they may be

  in the form of sterile isotonic saline aqueous solutions.

  Suspensions or solutions for intra-

  may contain, with the active compound, a vehicle acceptable for pharmaceutical use, for example sterile water, olive oil, ethyl oleate, glycols, for example propylene glycol, and, if desired, a proportion

  appropriate lidocaine hydrochloride.

  In forms for topical applications, for example creams, lotions or pastes for use in dermatological treatments, the active substance may be mixed with

  Oleaginous excipients or conventional emulsifiers.

  Solid forms for oral administration, for example tablets and capsules, may contain, with the active compound, diluents, for example lactose, dextrose, sucrose, cellulose, corn starch or starch potato; lubricants, for example silica, talc, stearic acid, magnesium or calcium stearate and / or polyethylene glycols; binders, for example

  starches, gum arabic, gelatin, methyl-

  cellulose, carboxymethylcellulose, polyvinylpyrrolidone; disintegrants, for example starch, alginic acid, alginates, sodium starch glycolate; effervescent mixtures; dyes; sweetening agents; agents

  wetting agents, for example lecithin, polysorbates,

  sulphates; and, in general, non-toxic and pharmacologically inactive substances commonly used

  in pharmaceutical compositions. These pharmaceutical compositions

  may be prepared in a known manner, for example by mixing, granulating, tabletting, coating with

  sugar or application of a coating film.

  The invention also comprises a process for preparing a pharmaceutical composition as described above, which method comprises combining an effective proportion of the active substance of formula (IA) with an acceptable vehicle and / or diluent.

for pharmaceutical use.

  In addition, and in accordance with the invention, a method for treating viral infections and tumors has been found in a patient in need of such treatment, which method comprises

  administer to said patient a composition according to the invention.

  The abbreviations DMSO, THF, CDI, DMF, DCC, DCU and ACOH used hereinafter respectively represent dimethylsulfoxide, tetrahydrofuran, carbonyldiimidazole, dimethylformamide,

  dicyclohexylcarbodiimide, dicyclohexylurea and acetic acid.

  The following examples illustrate the invention without

however, limit its scope.

Example 1

  To an aqueous solution of N, N-dimethylaminopropylamine (2.03 g in 40 ml of water) and sodium bicarbonate (3.36 g) is added at room temperature with stirring a solution of 4 g of sodium chloride. N-methyl-4-nitropyrrole-2-carboxylic acid in 5 ml of benzene. The mixture is stirred for 2 hours at room temperature, saturated with sodium chloride and extracted twice with 50 ml of benzene. The dried organic extracts are concentrated in vacuo and the residue is crystallized from petroleum ether.

  Lightweight; performance; 3.5 g of 3-EN-methyl-4-nitropyrrole-2-carboxamide

  mido] pure propyldimethylamine, white needles melting at 118-120C.

  NMR (DMSO-d6): δ 1.60 (2H, m); 2.12 (6H, s); 3.23 (2H, t); 3.20 (2H, m); 3.88 (3H, s); 7.37 (1H, d);

8.08 (1H, dl); 8.35 (1H, ti).

Example 2

  3.4 g of the compound of Example I are dissolved in 40 ml of ethanol and 20 ml of dilute hydrochloric acid and reduced on a

  5% palladium on charcoal catalyst under hydrogen pressure.

  3.5 bar gene in a Parr apparatus. 20 ml of water are added and the catalyst is filtered. The solution is concentrated and the residue is redissolved in 40 ml of water. 4 g of sodium bicarbonate is added

  then a solution of 2.8 g of N-methyl-4-

  nitropyrrole-2-carboxylic acid in 20 ml of benzene. The mixture is stirred for about 2 hours at room temperature and then extracted with chloroform. The dried organic extracts are concentrated in vacuo and the residue is purified by column chromatography (95% chloroform / ethanol / NH 4 OH, 75: 25: 0.6); we obtain 4.7 g

  3-EN-methyl-4- (N-methyl-4-nitropyrrole-2-carboxamido) pyrrole

  2-carboxamido] propyldimethylamine as a solid substance

yellow melting at 178-180C.

  NMR (CDCl3) δ: 1.74 (2H, m); 2.30 (6H, s); 2.49 (2H, t); 3.44 (2H, m); 3, 88 (3H, s); 3.99 (3H, s); 6.58 (1H, d); 7.21 (1H, d); 7.38 (1H, d);

7.6 (1H, 1); 8.80 (1H, sI).

  By a similar procedure, the following compounds were obtained: 3EN-methyl-4- [N-methyl-4-EN-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldimethylamine melting at 175 ° C (decomposition); NMR (DMSO-d6) δ: 1.63 (2H, m); 2.22 (6H, s); 2.38 (2H, t); 3.16 (2H, dt); 3.80 (3H, s); 3.85 (3H, s); 3.87 (3H, s); 3.97 (3H, s); 6.80-7.30 (6H, m); 7.59 (1H, d); 8.04 (1H, t); 8.16 (1H, d); 9.84 (1H, if); 9.95 (1H, sI); 10.26 (1H, sI);

  3- [N-methyl-4-EN-methyl-4-S [N-methyl-4-EN-methyl-4-nitropyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] propyldimethylamine, melting at 195 ° C (dec); NMR (DMSO-d6) δ: 1.64 (2H, m); 2.13 (6H, s); 2.27 (2H, t); 3.20 (2H, dt); 3.80 (3H, s); 3.85 (3H, s); 3.88 (3H, s); 3.98 (3H, s); 6.82 (1H, d); 7.04 (2H, m); 7.18 (1H, d); 7.26 (2H, d); 7.58 (1H, d); 8.18 (1H, d); 8.02 (1H, t); 9.86 (1H, s); 9.94 (1H, s); 10.25 (1H, s);

  O- [N-methyl-4-EN-methyl-4-nitropyrrole-2-carboxamide hydrochloride

  mido] pyrrole-2-carboxamido] propionamidine;

  g- [N-methyl-4- [N-methyl-4- [N-methyl-4-nitropyrrolid] hydrochloride;

  Z-carboxamido] pyrrole-2-carboxamidoapyrroLe-2-carboxamido] propionitrile

namidine;

  0- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-] hydrochloride

  nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrote-2-carboxamido] propionamidine.

ExempLe 3

  900 mg of g- [N-methyl-4- hydrochloride is hydrogenated.

  [N-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido3pro-

  pionamidine, dissolved in 150 ml of ethanol, 75 ml of water and 9 ml of 2N HCl at the Parr apparatus for 45 minutes with hydrogen at a pressure of 3.1 bar at room temperature on a catalyst. at 10% of palladium on charcoal. The catalyst is filtered and the filtrate is evaporated in vacuo; 930 mg of the dichlorhydrate are obtained

  N- [N-methyl-4-EN-methyl-4-aminopyrrole-2-carboxamido] pyrrolidine

  Crude 2-carboxamido] propionamidine. The residue is redissolved in 60 ml of methyl alcohol, cooled to -200 ° C. and heated with 12 ml of ethylene oxide. After 15 minutes, the temperature is allowed to rise and then the mixture is left at room temperature overnight. The solution is evaporated to dryness; after chromatography

  on SiO 2 Washed with HCl, 800 mg of hydrochloride of 0- [N-

  methyl-4-EN-methyl-4- [N, N-bis- (2-hydroxyethylamino)] pyrrole-2-

  pure carboxamido] pyrrole-2-carboxamido] propionamidine; mass spectrum: m / e 419 (M +); 420 (M ++ 1); 1 H NMR (dimethyl-6-sulfoxide) 6: 2.63 (2H, t); 2.90-3.80 (10H, m); 4.55 (2H, L); 6.30 (1H, d); 6.52 (1H, d); 6.92 (1H, d); 7.12 (1H, d); 8.20 (1H, t); 8.70 (2H, sL); 9.01 (2H, sL); 9.63 (1H, s); UV (95% EtOH) m: 245, mp = 16352 max Amax 292, = 15,070 By a similar procedure, the following compounds were obtained: N-deformyl-N- [N-methyl-4] hydrochloride [N, N-bis (2-hydroxyethylamino) pyrrole-2-carboxamido] distamycin A;

  3-EN-methyl-4-EN-methyl-4- [N, N-bis (2-hydroxyethyl) hydrochloride

  amino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyl-

amine;

  3-EN-methyl-4-EN-methyl-4- [N-methyl-4-EN, N-bis-

  (2-hydroxyethylamino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  3-EN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- hydrochloride

  EN, N-bis (2-hydroxyethylamino)] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

dimethylamine.

Example 4

  An ice bath is cooled with stirring

  solution of 717 mg of 0-EN-methyl-4- [N-methyl-4- hydrochloride

  EN, N-bis (2-hydroxyethylamino)] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] propionamidine in 10 ml of dry pyridine and treated under nitrogen with 2.7 ml of a 1.27 M solution of methanesulfonyl chloride in pyridine with stirring at 5 C for min. The reaction is quenched with methyl alcohol and allowed to come to room temperature and then evaporated to dryness. The crude product is chromatographed on silica; 440 mg is obtained

  of 1-EN-methyl-4-EN-methyl-4-EN, N-bis (2-chloroethyl) hydrochloride

  amino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine. 1H NMR (dimethyl-6-sulfoxide) δ: 2.63 (2H, t); 3.30-3.80 (10H, m); 3.78 (3H, s); 3.81 (3H, s); 6.42 (1H, d); 6.55 (1H, d); 6.92 (1H, d); 7.17 (1H, d); 8.20 (1H, t); 8.70 (2H, sI); 9.02 (2H, sI); 9.68 (1H, s); U.V. (95% EtOH):> max 245, E = 17,373;

Amax 293, 6 = 450.

  The following compounds could be obtained by analogous procedure:

  1-EN-methyl-4- [N-methyl-4-EN-methyl-4-EN, N-bis-

  (2-chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propionamidine;

  N-deformyl-N-EN-methyl-4- [N, N-bis (2-chloroethyl) hydrochloride

  amino)] pyrrole-2-carboxamido] distamycin A; NMR (DMSO-d6) δ: 2.63 (2H, t); 3.20-3.9 (10H, m); 3.80-3.85 (3H, s); 6.46 (1H, d); 6.58 (1H, d); 6.90-7.30 (6H, m); 8.20 (1H, t); 8.73 (2H, 1); 9.00 (2H, 1); 9.70 (1H, s); 9.90 (2H, s);

  N-deformyl-N-EN-methyl-4-EN-methyl-4- [N, N-bis] hydrochloride

  (2-chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

distamycin A;

  N-deformyl-N- [N-methyl-4- [N-methyl-4-EN-methyl-4- hydrochloride

  [N, N-bis (2-chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] distamycin A;

  3- [N-methyl-4-EN-methyl-4-EN, N-bis (2-chloroethyl) hydrochloride

  amino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyl-

amine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4-EN, N-bis] -hydrochloride

  (2-chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  3-EN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4- hydrochloride

  [N, N-bis (2-chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

  dimethylamine. EXAMPLE 5 To an ice-cold solution of 0.404 g of

  3-EN-methyl-4- (N-methyl-4-aminopyrrole) -2-dihydrochloride

  carboxamido) pyrrole-2-carboxamido] propionamidine in 5 ml of DMF and 320 mg of 2,4,5-trichlorophenyl-N-methyl-N-nitrosocarbamate [prepared as described in J. Med. Chem. 25, 178 (1982)], one

  added dropwise a solution of 0.164 ml of diisopropyl-

  ethylamine in 8 ml of DMF. The solution is stirred for 1 hour at 0 ° C.

  The reaction mixture is concentrated under vacuum and the

2 5 8 5 0 18

  residue by column chromatography; yield: 251 mg of

  -EN-methyl-4-EN-methyl-4- (3-methyl-3-nitroso) hydrochloride

  ureido) pyrrole-2-carboxamido] pyrrole-2-carboxamido3propionamidine. U.V. (95% EtOH): Max 241, E = 21611 max 293, = 28207> Amax 293, 207 I.R. (KBr): NMR (DMSO-d6) cm1 3500-2800; 2500-2200; 1450; 970; 650: 2.59 (2H, m); 3.15 (3H, s); 3.48 (2H, m); 3.79 (3H, s); 3.85 (3H, s); 7.01-7.31 (4H, m); 8.61 (2H, 1); 8.97 (2H, 1); 9.91 (2H, 1);

, 61 (1H, s1).

  The following compounds could be obtained by an analogous procedure:

  3- [N-methyl-4- [N-methyl-4-E3- (2-chloroethyl) -3-hydrochloride

  nitrosoureido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionitrile

  namidine, NMR (DMSO-d6) δ: 2.61 (2H, t); 3.50 (2H, m); 3.69 (2H, t); 3.81 (3H, s); 3.87 (3H, s); 4.19 (2H, t); 6.90-7.25 (4H, m); 8.19 (1H, t); 8, 55-10.72 (6H, m);

  3- [N-methyl-4- [N-methyl-4- [3-methyl-3-nitroso] hydrochloride

  ureido] pyrrole-2-carboxamidolpyrrole-2-carboxamido] propyldiméthyL-

amine;

  3- [N-methyl-4-EN-methyl-4- [3- (2-chloroethyl) -3-hydrochloride

  nitrosoureido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

  dimethylamine; NMR (DMSO-d6) δ: 1.84 (2H, m); 2.70 (6H, s); 2.90-3.90 (6H, m) 3.81 (3H, s); 3.87 (3H, s); 4.18 (2H, t); 6.85-7.30 (4H, m); 8.15 (1H, t); 8.93-9.75 (3H, m);

  3-EN-methyl-4- [N-methyl-4-EN-methyl-4- (3-methyl) -hydrochloride

  3-nitrosoureido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine; NMR (DMSO-d6) δ: 1.80 (2H, m); 2.53 (6H, s); 2.78 (2H, m); 3.18 (3H, s); 3.20 (2H, m); 3.80 (3H, s); 3.85 (3H, s); 3.88 (3H, s); 6.85-7.25 (6H, m); 8.10 (1H, t); 9.85-10.70 (3H, m);

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4- [3- (2-

  chloroethyl) -3-nitrosoureido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine; NMR (DMSO-d6) δ: 1.98 (2H, m); 2.65 (6H, s); 2.90 (2H, t); 3.81 (3H, s); 3.87 (3H, s); 3.89 (3H, s); 4.09 (2H, t); 6.85-7.30 (6H, m); 8.12 (1H, t); 9.80-10.8 (3H, m);

  N-deformyl-N-EN-methyl-4- (3-methyl-3-nitrosoureido) hydrochloride

  pyrrole-2-carboxamido] distamycin A;

  N-deformyl-N- [N-methyl-4- [3- (2-chloroethyl) -3-hydrochloride

  nitrosoureido] pyrrole-2-carboxamido] distamycin A;

  3-EN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4- hydrochloride

  (3-methyl-3-nitrosoureido) pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine; NMR (DMSO-d6) δ: 1.90 (2H, m); 2.73 (6H, s); 3.19 (3H, s); 3.82 (3H, s); 3.84 (3H, s); 3.85 (3H, s); 3.86 (3H, s); 6.90-7.30 (8H, m); 8.13 (1H, t); 9, 88-10.70 (4H, m);

  3-EN-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4- hydrochloride

  E3- (2-chloroethyl) -3-nitrosoureido] pyrrote-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

  dimethylamine; NMR (DMSO-d 6 / CDCl 3) 6: 1.90 (2H, m); 2.60 (6H, s); 2.85 (2H, t); 3.15-4.00 (16H, m); 4.22 (2H, t); 6.80-7.30 (8H, m); 8.00 (1H, t); 9.63 (1H, s); 9.70 (1H, s); 9.77 (1H, s); , 48 (1H, s);

  1- [N-methyl-4- [N-methyl-4- (oxirannecarboxamido) hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine;

  3-EN-methyl-4-EN-methyl-4- (oxirannecarboxamido) hydrochloride

  pyrrole-2-carboxamido) pyrrole-2-carboxamido] propyldiméthylamine;

  3-IN-methyl-4-EN-methyl-4- [N-methyl-4- (oxirannecarboxamido) pyrrole

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

dimethylamine.

Example 6

  To a solution of 765 mg of (2R, 3R) -3-methyl-

  In 20 ml of dry THF, cooled to -20 ° C., 0.825 ml of N-methylmorpholine and 0.920 ml of pivaloyl chloride are added. The suspension obtained is stirred for 20 min at -20 ° C. and then poured into a cooled solution of 2.6 g of

  3-EN-methyl-4-EN-methyl-4-EN-methyl-4-amino-dichlorohydrate

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldimethylamine in 50 ml of DMF and 0.4 g of sodium bicarbonate. The mixture is stirred for 30 min at 0 ° C. and then for 4 hours at room temperature. The solvents are evaporated to dryness under vacuum and the residue is chromatographed on silica (solvent: CHCl3 / CH3OH / HCl2N,

  100: 100: 1); 1.4 g of 3- [N-methyl-4- hydrochloride are obtained

  [N-methyl-4-EN-methyl-4-E3-methyl- (2R, 3R) oxirannecarboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  propyldiméthylamine. NMR (DMSO-d6) δ: 1.25 (3H, d); 3.3 (1H, m); 3.60 (1H, d);

[J = 4.7 Hz (cis)].

  The following compounds can be obtained by analogous procedure:

  N-deformyl-N- [N-methyl-4- (oxirannecarboxamido) hydrochloride

  pyrrole-2-carboxamido] distamycin A;

  3-EN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- hydrochloride

  (Oxirannecarboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4- (cyclopropylcarboxamido) hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine;

  3-EN-methyl-4- [N-methyl-4- (cyclopropylcarboxamido) hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4- [N-methyl-4- (cyclopropyl) hydrochloride

  carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

carboxamido] propyldiméthylamine;

  N-deformyl-N- [N-methyl-4- (cyclopropylcarboxamido) hydrochloride

  pyrrole-2-carboxamido] distamycin A;

  3-EN-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4- hydrochloride

  (Cyclopropylcarboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4- (3-methyloxirancarboxylic acid) hydrochloride

  mido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine;

  3-EN-methyl-4-EN-methyl-4- (3-methyloxynecarboxylic acid) hydrochloride

  mido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyLdiméthyLamine;

  3-EN-methyl-4-EN-methyl-4-EN-methyl-4- (3-methyloxidin) hydrochloride

  rannecarboxamido) pyrrole-2-carboxamido] pyrrote-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine;

  N-deformyl-N-EN-methyl-4- (3-methyloxirancarboxylic acid) hydrochloride

  mido) pyrrole-2-carboxamido] distamycin A;

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- hydrochloride

  (3-méthyloxirannecarboxamido) pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldi-

methylamine;

  f- [N-methyl-4- [N-methyl-4- (2-chloroethylcarboxamido) hydrochloride)

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine;

  3- [N-methyl-4- [N-methyl-4- (2-chloroethylcarboxamido) hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3- [N-methyl-4- [N-methyl-4- [N-methyl-4- (2-chlorohydrochloride) hydrochloride

  ethylcarboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyLdiméthylamine;

  N-deformyl-N- [N-methyl-4- (2-chloroethylcarboxamido) hydrochloride

  pyrrole-2-carboxamido] distamycin A;

  3- [N-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4- hydrochloride

  (2-chloroéthylcarboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  1- [N-methyl-4-EN-methyl-4- [1- (aziridine) carboxamido] hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine;

  3-EN-methyl-4-EN-methyl-4- [1- (aziridine) carboxamido] hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyLamine;

  3- [N-methyl-4- [N-methyl-4-EN-methyl-4- [1- (aziridine) hydrochloride]

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido3pyrroLe-2-

carboxamido] propyldiméthylamine;

  N-deformyl-N- [N-methyl-4- [1- (aziridine) carboxamido] hydrochloride

  pyrrole-2-carboxamido] distamycin A;

  3-EN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4- hydrochloride

  E [1- (aziridine) carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrote-2-carboxamido] propyldiméthylamine.

Example 7

  To a solution of 2.3 g of La dihydrochloride

  3-IN-methyl-4- [N-methyl-4- [N-methyl-4-aminopyrrole-2-carboxamidoJ-

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldimethylamine in 200 ml of water and 1.5 g of sodium bicarbonate is added with stirring at room temperature a solution of 1.0 g of N-methyl chloride 4-nitropyrrole-2-carboxylic acid in

mi of THF.

  The mixture is refluxed with stirring for 2 h. The reaction mixture is evaporated in vacuo, the residue is taken up in water, adjusted to pH 13 with 2N NaOH and extracted with a CHCl 3 / methanol mixture, 70:30. The dried organic extracts are concentrated in vacuo and the residue is purified by column chromatography (CHCl 3 / methanol / NH 4 OH, 70: 30: 1); we

  2.6 g of 3- [N-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl]

  4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

* carboxamido] pyrrole-2-carboxamido] propyldimethylamine as a yellow solid melting at 195 ° C (decomposition); NMR (DMSO-d6) b: 1.64 (2H, m); 2.13 (6H, s); 2.27 (2H, t); 3.20 (2H, dt); 3.80 (3H, s); 3.85 (3H, s); 3.88 (3H, s); 3.98 (3H, s); 6.82 (1H, d); 7.04 (2H, m); 7.18 (1H, d); 7.26 (2H, d); 7.58 (1H, d); 8.18 (1H, d); 8.02 (1H, t);

  9.86 (1H, s); 9.94 (1H, s); 10.25 (1H, s).

  The following compounds could be obtained by analogous procedure:

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-

  nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine; NMR (DMSO-d6) δ: 1.68 (2H, m); 2.32 (6H, s); 3.81 (3H, s); 3.88 (9H, sI); 3.97 (3H, s); 6.8-7.3 (8H, m); 7.60 (1H, d); 8.04 (1H, tl); 8.18 (1H, d); 9, 85-10.27 (4H, 1, ss, NH); and

  3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-

  EN-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamidoJpyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propyldiméthylamine; NMR (DMSO-d6) δ: 1.68 (2H, m); 2.32 (6H, s); 3.81 (3H, s); 3.88 (9H, sI); 3.97 (3H, s); 6.8-7.3 (8H, m); 7.60 (1H, d); 8.04 (1H, tl); 8.18 (1H, d);

9.85-10.27 (4H, L, ss, NH).

Example 8

  800 mg of 3-EN-methyl-4-EN-methyl-4- is dissolved

  EN-methyl-4- [N-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

  dimethylamine in a mixture of 70 mL of methanol, 30 mL of water and 3 mL of 1N HCl and reduced on a 10% palladium catalyst

  on charcoal under a hydrogen pressure of 3.5 bar.

  The catalyst is filtered, the solution concentrated in vacuo and the residue is crystallized from ethyl acetate / ethanol; 760 mg of the dihydrochloride of

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-aminopyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] propyldimethylamine, NMR (DMSO-d6) b: 1.88 (2H, m); 2.72 (6H, s); 3.81 (3H, s); 3.85 (3H, s); 3.86 (3H, s); 3.90 (3H, s); 6.9-7.3 (8H, m); 8.13 (1H, tD); 8.87 (1H, sI);

  9.91 (1H, sI); 10.09 (1H, sI); 10.2 (3H, L, MH).

  The following compounds could be obtained by analogous procedure:

  3- [N-methyl-4- [N-methyl-4-aminopyrrole-2-carboxamide] dihydrochloride

  mido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-EN-methyl-4-EN-methyl-4- [N-methyl-4-aminopyrrole dihydrochloride

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl

dimethylamine;

  3-EN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4- dichlorhydrate

  [N-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl-

dimethylamine; and

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-] dihydrochloride

  [N-methyl-4-EN-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido) propyLdiméthylamine.

Example 9

  150 mg of sodium bicarbonate is added to a solution of 3-EN-methyl-4-EN-methyl-4-EN-methyl-dihydrochloride.

  4- [N-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldimethylamine (500 mg in 25 mL of anhydrous methanol) and the suspension is stirred

  for 1 h at room temperature.

  The reaction mixture is cooled to -40 ° C. and a solution of N-formylimidazole in THF (prepared as described in JOC (1985), 3774-3779 starting from 1.625 g of CDI, is added dropwise over 15 minutes. 0.38 ml of formic acid and 15 ml

anhydrous THF). The temperature is allowed to rise to 10 C in 60 min. We evaporate the mixture

  reaction in vacuo and the residue is chromatographed on silica; we obtain 460 mg of

  3-EN-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4- hydrochloride

  formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  pure carboxamido] pyrrole-2-carboxamido] propyldimethylamine in the state

of yellow solid substance.

  NMR (DMSO-d6) δ: 1.90 (2H, m); 2.72 (6H, s); 3.84 (12H, if); 6.8-7.3 (8H, m); 8.12 (1H, tl); 8.13 (1H, d);

9.88 (3H, si); 10.04 (1H, sI).

  The following compounds were obtained by an analogous procedure:

  3-EN-methyl-4-EN-methyl-4-formylaminopyrrole-2-dihydrochloride

  carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;

  3-EN-methyl-4- [N-methyl-4-EN-methyl-4-formyl] dihydrochloride

  aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

mido] propyldiméthylamine;

  3- [N-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4- hydrochloride

  [N-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

propyldiméthylamine; and also

  3-EN-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4- hydrochloride

  [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamido) pyrrole

  2-carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldiméthyLamine.

Example 10

  A solution of 2 g of distamycin A hydrochloride in 60 ml of methanol is treated with 0.5 ml of aminoacetaldehyde dimethylacetal and allowed to stand at room temperature.

  for 5 hours. A further 10% of dimethyl

  aminoacetaldehyde acetal and the solution was refluxed for 16 h. The solvent is removed in vacuo and the crude product is redissolved in 100 ml of a 1N aqueous solution of oxalic acid and kept at 70 ° C. for 4 hours. The aqueous solution is evaporated to dryness and the solid residue is washed a few times with acetone, collected and

  treated with an excess of an alcoholic solution 3.5 N HCl.

  The solvent is removed in vacuo and the crude product is taken up in acetone, filtered and collected;

  yield: 1.1 g (52.5%) of 0- [N-methyl-4- hydrochloride]

  EN-methyl-4-EN-methyl- (4-formylamino) pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl --- {2-imidazole]. NMR (DMSO-d6) δ: 2.83 (2H, t1); 3.50 (2H, m); 3.82 (3H, s); 3.85 (6H, s); 6, 80-7.25 (8H, m); 8.10 (1H, tt);

  8.13 (1H, s); 9.87 (2H, sI); 10.00 (1H, sl).

Example 11

  A solution of 200 mg of hydrochloride of

  distamycin A in 4 ml of methanol per 0.1 ml of ethylene

  diamine. The solution is kept at room temperature overnight and then evaporated under vacuum. The residue is taken up in 30 ml of acetone, stirred for 30 min and filtered; we get 20 mg

  of 1-EN-methyl-4-EN-methyl-4- [N-methyl-4-formyl] hydrochloride

  aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] ethyl-E2- (2-imidazoline)], NMR (DMSO-d6) δ: 2.68 (2H, t1); 3.52 (2H, dl); 3.76 (4H, if); 3.80 (3H, s); 3.83 (6H, s); 6.8-7.3 (6H, m); 8.12 (1H, d); 8.27 (1H, ti); 9.90 (2H, if);

, 11 (1H, sl).

  The following compounds were obtained by an analogous procedure:

  1- [N-methyl-4-EN-methyl-4- [N-methyl-4-formylamino] hydrochloride

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  Ethyl-E2- (3,4,5,6-tetrahydropyrimidine)], NMR (DMSO-d6) δ: 1.75 (2H, m); 2.60 (2H, t); 3.00-3.70 (6H, m); 3.81 (3H, s); 3.84 (6H, s); 6.80-7.30 (6H, m); 8.12 (1H, d); 8.25 (1H, t); 9.90 (2H, s); , (1H, s); and

  3- [N-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrroLe-2-carboxamide

  mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl-E2- (4,5

  dihydro) -oxazole], NMR (DMSO-d6) δ: 2.42 (2H, t); 3.42 (2H, m); 3.5-4.40 (4H, m); 3.80 (3H, s); 3.85 (6H, s); 6.80-7.30 (6H, m); 8.00 (1H, t); 8, 15 (1H, d); 9.90 (2H, s);

, 00 (1H, s).

Example 12

  A solution of 2 g of distamycin A hydrochloride in 100 ml of methanol and 8 ml of 20% NaOH (d = 1.22) is refluxed for 8 hours. 8 mL cold solution is added

23% aqueous HCl.

  The mixture obtained is concentrated under vacuum: a red solid substance precipitates; it is filtered and dried at

the oven at 40 under vacuum.

  The red solid (1.9 g) was redissolved in 66 mL of formamide and 6.6 mL of ethyl formate. The solution is refluxed for 2 hours. It is concentrated to dryness under high vacuum (0.1 mm Hg) and the oily residue is purified on silica (CHCl 3 /

  methanol / 2N HCl, 15: 15: 0.3); 920 mg of 0- [N-methyl-

  4- [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propionic, NMR (DMSO-d6) δ: 2.36 (2H, tL); 3.40 (2H, m); 3.80 (9H, s); 6.8-7.3 (6H, m); 7.84 (1H, tL); 8, 12 (1H, d);

  9.89 (1H, s); 9.94 (1H, s); 10.20 (1H, s).

Example 13

  1.9 g of 9-EN-methyl-4-EN-methyl-4- acid are dissolved

  EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propionic acid in 20 ml of DMF and treated with 600 mg of N-hydroxysuccinimide and 1.2 g of DCC. The mixture is stirred at ambient temperature for 7 hours. The DCU is filtered and the DMF is distilled at 35 ° C. under vacuum. The waxy residue is redissolved in the DNF and cooled to 5 ° C. in an ice bath. A solution of 0.3 g of NaBH 4 in 5 ml of water is added dropwise and the mixture is stirred at 5 ° C. for 2 h. The excess of NaBH 4 is destroyed by AcOH

  and the mixture is concentrated in vacuo.

  The residue is purified on silica (CHCl 3 / methanol, 9: 1);

  0.52 g of f- [N-methyl-4- [N-methyl-4- [N-methyl-4-] alcohol are obtained.

  formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] propyl, NMR (DMSO-d6) δ: 1.67 (2H, m); 3.80 (3H, s); 3.86 (6H, s); 4.4 (1H, tl); 6.84 (1H, d); 6.91 (1H, d); 7.05 (1H, d); 7.21 (3H, m); 7.92 (1H, tl); 8.12 (1H, d); 9.85 (1H, sL); 9.88 (1H, sI);

, 02 (1H, sI). -

Exemption 14

  To a solution of 469 mg of alcohol 0-EN-methyl-4-

  EN-methyl-4- [N-methyl-4-formylaminopyrrole-2-carboxamido3pyrrole-

  2-carboxamido] pyrrole-2-carboxamido] propyl in 10 ml of DMF, cooled to 0 ° C., is added under stirring under a nitrogen atmosphere.

  once 536 mg of 1-deoxy-1-O-chloro-3,4-bis-trifluoroacetyl-

  daunosamine. In the solution obtained, a solution of 385 mg of Ag (CF 3 SO 3) in 5 ml of DMF is added dropwise. The suspension is stirred for 1 h at 0 ° C., then filtered and treated.

  solution with 10 ml of 2N NaOH and then stirred for 3 h at 0 ° C.

  Filtered again and the solution evaporated to dryness under vacuum. The residue is chromatographed on Al 2 O 3 acid (CHCl 3 / methanol, 9: 1);

  230 mg of 1 - [(3-amino-2,3,6-trideoxy-α-L-lyxo-hexa) is obtained

  pyranosyl) oxy] trifluoroacetate of 3- [N-methyl-4- [N-methyl-4-]

  [N-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] propane, NMR (DMSO-d6) δ: 1.08 (3H, d); 1.74 (4H, m); 3.81 (3H, s); 3.85 (6H, s); 4.83 (1H, s); 5.40 (1H, d); 6.8-7.3 (6H, m); 7.95 (1H, tL); 8.12 (1H, d); 8E3H, tl (NH)]; 9.85 (1H, sI); 9.88 (1H, if);

, 04 (1H, if).

Example 15

  Tablets each weighing 0.250 g and containing 50 ml of the active substance can be prepared by operating as follows: composition (per 10,000 tablets)

  3- [N-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-nitro-

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-

  carboxamido] pyrrole-2-carboxamido] propyldimethylamine 500 g lactose 1400 g corn starch 500 g talc 80 g magnesium stearate 20 g

  3-EN-methyl-4- [N-methyl-4- [N-methyl-4- is mixed

  EN-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole

  2-carboxamido] pyrrole-2-carboxamido] propyldimethylamine, lactose and half of the corn starch; the mixture is forced through a sieve with a mesh size of 0.5 mm. In addition, 10 g of corn starch are suspended in 90 ml of hot water and

  uses the paste obtained to put the powder in the form of granules.

  The granules are dried, passed through a sieve with a mesh size of 1.4 mm, then the remainder of the starch, talc and magnesium stearate are added, the mixture is carefully mixed and the mixture is brought to the state.

of tablets.

Example 16

  Capsules each containing 0, 200 g and 20 mg of active substance can be prepared in the following manner: Composition per 500 capsules:

  A- [N-methyl-4-EN-methyl-4- [N-methyl-4- hydrochloride]

  (4-formylamino) pyrrole-2-carboxamido] pyrrole-2-carboxamide

  mido] pyrrole-2-carboxamido] ethyl- [2-imidazole] 10 g lactose 80 g corn starch 5 g magnesium stearate 5 g The mixture can be introduced into capsules of

  hard gelatin in two parts at a rate of 0.200 g per capsule.

ExempLe 17

  Composition for intramuscular injection at 25 mg / ml A pharmaceutical composition can be prepared

  injectable by dissolving 25 of 1 - [(3-amino-2,3,6-trideoxy-a)

  3- [N-methyl-4- L-lyxo-hexapyranosyl) oxy] trifluoroacetate

  EN-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamido] -

  pyrrole-2-carboxamido] pyrrole-2-carboxamido] propane in 1000 ml sterile propylene glycol and introducing into ampoules

from 1 to 5 ml.

Claims (26)

  1. A compound corresponding to the following formula (I): H > 0 N> 4 | (I) N Re C-N-R CINl 2 RR1 O R1 0   wherein n is 0 or a number of I to 4; R represents a) NHR3, R3 representing: a ') -CON (NO) R4, R4 representing an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') -CO (CH 2) m -R 5, wherein R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or α, β-unsaturated alicyclic lactone and m is 0 or at a number from 1 to 4; / R6 b) -N, R6 and R7 being identical and representative R7   each is an oxiran-methyl, aziridimethyl or C2-C4 alkyl group substituted in the 2-position by a halogen or -SO2R8 group, wherein R8 represents a C1-C4 alkyl or phenyl group, or one of symbols R6 and R7 represent hydrogen and the other has one of the meanings just indicated; c) -NO2; d) -NH2; or e) -NHCHO; each of the symbols R 1 represents, independently of the others, a hydrogen atom or a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic or acidic unit or a free or glycosylated hydroxy group, with the provisos that: (i) R can not have the meanings given above under a) and b) when n is 1 and that, simultaneously, R2 represents -CH2-CH2-C NH2 (ii) R can not represent -NO2 nor -NH2 nor -NH-CHO when NH   R2 represents an -alk-C N group, in which alk NR 'R "   is a C1-C6 alkyl group and each of R 'and R "is, independently, a hydrogen atom or a methyl group, or where, n being 0 or 1, CH -3 R2 represents a group - (CH 2) PN H, where p is 2 or 3, and (iii) R can not represent NH 2 when, simultaneously, n is 0 or 1, each of the symbols R 1 represents a methyl group and R 2 represents a -CH2-CH2-COOH group,   and its pharmaceutically acceptable salts.   2. A compound of formula (I) according to claim 1, wherein, subject to restriction (i) of claim 1, n is 0 or a number of 1 to 4; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, R4 represents an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') -CO (CH 2) m -R 5, where R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or 2,3-unsaturated alicyclic lactone residue, and m is 0 or a number from 1 to 4; or R 6 b) -N, wherein R 6 and R 7 are the same and R 7 is each oxiran-methyl, aziridin-methyl, or C 2 -C 4 alkyl substituted in the 2-position with halogen or -OSO 2 R 8 wherein R8 is C1-C4alkyl or phenyl, or one of R6 and R7 is hydrogen and the other has one of the meanings just defined; each of the symbols R 1 representing, independently of the others, hydrogen or a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic or acidic unit or with a free or glucosylated hydroxy group,   and its pharmaceutically acceptable salts.   3. A compound of formula (I) according to claim 2, wherein taking into account the restriction (i) of claim 1, n is 0, I or 2; R represents a) -NHR3, where R3 represents a ') -CON (NO) R4, R4 represents a C1-C4 alkyl group substituted by a halogen, or b') -CO (CH2) m -R5, where R5 represents a halogen, oxiranyl, 1-aziridinyl, cyclopropyl or a 1-unsaturated alicyclic lactone residue, and m is 0, 1 or 2; or else / R6 b) -N, R6 and R7 being identical and representing R7   each an oxirane-methyl group, 1-aziridinyl-   methyl or a C 2 -C 4 alkyl group substituted in the 2-position by halogen or -OSO 2 R 8, wherein R 8 is C 1 -C 4 alkyl; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic unit,   and its acid salts acceptable for pharmaceutical use.   4. A compound of formula (I) or a salt thereof as claimed in claim 2, wherein the basic terminal unit of the substituent R2 is selected from amino, mono- or di-C 1 -C 3 alkyl groups. C6) amino; amidino; -N = N-N '; and CH3   heterocycles containing nitrogen.   5. A compound selected from the group consisting of:   9- [N-methyl-4- [N-methyl-4- (3-methyl-3-nitrosoureido) pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propionamidine_;   0-IN-methyl-4- [N-methyl-4- [3- (2-chloroethyl) -3-nitrosoureido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionamidine;   3- [N-methyl-4- [N-methyl-4- [3-methyl-3-nitrosoureido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propytdiméthylamine;   3- [N-methyl-4- [N-methyl-4-U3- (2-chloroethyl) -3-nitrosoureido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4- [N-methyl-4-EN-methyl-4- (3-methyl-3-nitrosoureido) -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] - propyldiméthylamine;   3-IN-methyl-4- [N-methyl-4- [N-methyl-4- [3- (2-chloroethyl) -3-   nitrosoureido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrote- 2-carboxamido] propyldiméthylamine;   N-deformyl-N-EN-methyl-4- (3-methyl-3-nitrosoureido) pyrrole-2- carboxamido] distamycin A;   N-deformyl-N- [N-methyl-4- [3- (2-chloroethyl) -3-nitrosoureido] -   pyrrole-2-carboxamido] distamycin A;   3-IN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4 (3-methyl-3-   nitrosoureido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole   2-carboxamido] pyrrole-2-carboxamido] propytdiméthylamine;   3-IN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4- [3- (2-chloroethyl) -   3-nitrosoureido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole   2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine-;   I-EN-methyl-4-EN-methyl-4- (oxirannecarboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propionamidine;   3-IN-methyl-4- [N-methyl-4- (oxirannecarboxamido) pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4- (oxirannecarboxamido) pyrrole   2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl- dimethylamine;   N-deformyl-N-EN-methyl-4- (oxirannecarboxamido) pyrrole-2-carboxamido] - distamycin A;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- (oxirannecarboxa-   mido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide   mido] pyrrole-2-carboxamido] propyldiméthylamine;   f-EN-methyl-4-EN-methyl-4- (cycLopropyLcarboxamido) pyrrole-2-carboxamide   midojpyrroLe-2-carboxamidojpropionamidine;   3-IN-methyl-4-EN-methyl-4- (cycLopropyLcarboxamido) pyrrole-2-carboxamide   mido] pyrrole-2-carboxamidoIpropyldiméthyLamine;   3-IN-methyl-4- [N-methyl-4-EN-methyl-4- (cyclopropylcarboxamido) -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] - propyldiméthylamine;   N-deformyl-N-EN-methyl-4- (cycLopropylcarboxamido) pyrrole-2-carboxamide mido] distamycin A;   3- [N-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4- (cyclopropyl-   carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole   2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   f-EN-methyl-4-EN-methyl-4- (3-méthyloxirannecarboxamido) pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propionamidine;   3- [N-methyl-4-EN-methyl-4- (3-méthyloxirannecarboxamido) pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4- [N-methyl-4- [N-methyl-4- (3-méthyloxirannecarboxamido) -   pyrrole-2-carboxamido] pyrrole-2-carboxamidojpyrrole-2-carboxamido] - propyldiméthylamine;   N-deformyl-N- [N-methyl-4- (3-méthyloxirannecarboxamido) pyrrole-2- carboxamido] distamycin A;   3- [N-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4- (3-méthyloxiranne-   carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   e-EN-methyl-4-EN-methyl-4- (2-chloroéthylcarboxamido) pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propionamidine;   3-IN-methyl-4-EN-methyl-4- (2-chloroéthylcarboxamido) pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4-EN-methyl-4- [N-methyl-4- (2-chloroéthylcarboxamido) -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] - propyldiméthylamine;   N-deformyl-N- [N-methyl-4- (2-chloroéthylcarboxamido) pyrrole-2- carboxamido] distamycin A;   3- [N-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4- (2-chloroethyl   carboxamido) pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   0- [N-methyl-4- [N-methyl-4-E1- (aziridine) carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propionamidine;   3- [N-methyl-4- [N-methyl-4- [1- (aziridine) carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4- [N-methyl-4- [N-methyl-4-1- (aziridine) carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] - propyldiméthylamine;   N-deformyl-N- [N-methyl-4-E1- (aziridine) carboxamido] pyrrote-2 carboxamido] distamycin A;   3-IN-methyl-4-EN-methyl-4-a-methyl-4- [N-methyl-4- [1- (aziridine) -   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole   2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   0- [N-methyl-4- [N-methyl-4- [N, N-bis (2-chloroethylamino)] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propionamidine;   3- [N-methyl-4- [N-methyl-4-EN, N-bis (2-chloroethylamino)] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4- [N-methyl-4-EN-methyl-4-EN, N-bis (2-chloroethylamino)] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] - propyldiméthylamine;   N-deformyl-N- [N-methyl-4-EN, N-bis (2-chloroethylamino)] pyrrole-2- carboxamido] distamycin A;   3- [N-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-EN, N-bis (2-   chloroethylamino)] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthyLamine;   and its acceptable salts for pharmaceutical use.   6. An acceptable salt for the pharmaceutical use of a   compound according to claim 5, this salt consisting of chlorhydrin   drate. A compound of formula (I) according to claim 1, wherein, subject to restrictions (ii) and (iii) of claim 1, n is 0 or 1 to 4; R represents -NO2, -NH2 or NHCHO; each of the symbols R 1 represents, independently of the others, hydrogen or a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic or acidic unit or with a free or glucosylated hydroxy group,   and its acceptable salts for pharmaceutical use.   A compound of formula (I) according to claim 7, wherein, subject to restrictions (ii) and (iii) of claim 1, n is 0 or a number of 1 to 4; R represents -NO2, -NH2 or -NHCHO; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a substituent   selected from amino groups; mono- and di- (C1-C6) alkyl -   Amino CH3; -N = N-N and heterocycles containing nitrogen; CH 2 COOH; CH2-OH; and -CH2-O-D, where D is a sugar residue or   amino-sugar, and its pharmaceutically acceptable salts.   9. A compound selected from the group consisting of:   3-IN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-nitropyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2- carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4-   nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-   carboxamido] pyrrole-2.carboxamido] pyrrole-2-carboxamido] propyl- dimethylamine ;:   3- [N-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-   EN-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-aminopyrrole-2-   carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamidolpyrroLe-2- carboxamido] propyLdiméthyLamine;   3-IN-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4-   aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl- dimethylamine;   3-IN-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4-   EN-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4-formylamino-   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4-   formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl- dimethylamine;   3- [N-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4- [N-methyl-4-   [N-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   f-EN-methyl-4-EN-methyl-4- [N-methyl- (4-formylamino) pyrrole-2   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamidoléthyl- [2-imidazole];   0- [N-methyl-4-EN-methyl-4- [N-methyl-4-formyLaminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (2-imidazoline)];   3- [N-methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl-   [2- (3,4,5,6-tetrahydropyrimidine)];   1- [N-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (4,5-dihydro) oxazole];   0- [N-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrrole-2- acid   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionic acid;   Alcohol 3-EN-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole]   2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl;   1 - [(3-amino-2,3,6-trideoxy-lyxo-L-t-hexapyrannosyl) oxy] trifluoroacetate   3-EN-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrrole acetate   2-carboxamido] pyrrole-2-carboxamidolpyrrole-2-carboxamido] propane;   and, if applicable, its acceptable salts for pharmaceutical use.   10. An acceptable salt for the pharmaceutical use of a   compound according to claim 9, this salt consisting of chlorine   hydrate. 11. A process for preparing a compound of formula (I) or a salt acceptable for the pharmaceutical use of such a compound according to claim 1, which process comprises: (A) reacting a compound of formula (II): CONH - R2 2   Wherein R1 and R2 have the meanings given in claim 1, except that restriction (iii) does not apply, and q is a number from 1 to 5, with a compound of formula (III); o.N 2O0 (III) R1   in which R1 has the meanings indicated in the   cation 1 and Z is a leaving group to give a compound of formula CI) wherein R is -NO 2; or (B) reducing a compound of formula (IV): 21 N   NRN t R. t 1 2 (IV) R1 - L R 'n 1 he R_ 0   v in which n. R 1 and R 2 have the meanings given in claim 1 except that n can not be 0 or 1 when each of R 1 is methyl and R 2 is CH 2 -CH 2 -COOH to give a compound of formula (I) wherein R is -NH2; or (C) formylating a compound of formula (V): HH H2 H2 1 1BoRR2 (V) -LNI-R2 Pl 0 _n a 2 R1 R1 0   wherein n, R1 and R2 have the meanings given in claim 1, except that restriction (iii) does not apply, to give a compound of formula (I) wherein R is -NH-CHO; or (D) reacting a compound of formula (V) in whichR1, R2 and n have the meanings given in claim 1, with a compound of formula (VI): Z'-C-N (NO) -R4 (VI)   in which R4 has the meanings indicated in the   cation 1 and Z 'is a leaving group to give a compound of formula (I) wherein R represents -NHR 3 and R 3 represents   -CON (NO) R4, R4 having the meanings indicated in the claim   cation 1, or (E) reacting a compound of formula (V) wherein R1, R2 and n have the meanings given in claim 1, with a compound of formula (VII): Z-CO- (CH2) m-R5 (VII) wherein R5 and m have the meanings given in claim 1 and Z has the meaning indicated above to give a compound of formula CI) wherein R is -NHR3 and R3 is -COCCH2) m-R5, m and R5 having the meanings given in claim 1; or CF) reacting a compound of formula CV) wherein R1, R2 and n have the meanings given in claim 1, with a compound of formula CVIII): X-CH-CH \ / 2 (VIII)   wherein X may be hydrogen, C1-C2alkyl or halomethyl to give a compound of formula (IX): N V N. X ^ OOH N -R2   R1 in which R1, R2 and n have the meanings indicated in the   claim 1 and each of the symbols X has a corresponding meaning   to that of X in the compound (VIII), then to convert a compound of the formula (IX) into a compound of the formula (I) wherein R 6 R represents -N, R 6 and R 7 having the meanings indicated in claim 1 after which, if desired, the R 2 unit of a compound of formula (I) above, whether or not satisfying the restriction indicated above, is modified so as to obtain a compound of formula (I ) having a different R2 unit and / or, if desired, salting a compound of formula (I) or obtaining a free compound from a salt and / or, if desired, separating a mixture of isomers of formula (I) to the individual isomers. 12. A pharmaceutical composition comprising a carrier and / or diluent acceptable for pharmaceutical use and, as an active substance, a compound of formula (IA) below: R H H R1 R 2 R R 0   wherein n is 0 or a number from 1 to 4; R represents a) NHR3, R3 represents: a ') -CON (NO) R4, R4 represents unsubstituted or halogen-substituted C1-C4 alkyl, or b') -CO (CH2) m-R5, R5 representing a halogen, an oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or α, β-unsaturated alicyclic lactone residue, and m is 0 or a number of 1 to 4; R   R6 b) -N, R6 and R7 being identical and representing R7   each an oxirane-methyl, aziridine-   methyl or C2-C4 alkyl substituted in the 2-position by halogen or -OSO2R8, wherein R8 is C1-C4 alkyl or   phenyl, or one of the symbols R6 and R7 represents   hydrogen and the other has one of the meanings   cations just given; c) -NO2; d) -NH2; or e) -NH-CHO; each of the symbols R 1 represents, independently of the others, hydrogen or a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated by a basic or acidic unit or by a free or glucosylated hydroxy group, with the following restrictions: (i) R can not have the meanings given above under a) and b) when n is 1 and simultaneously R2 / NH is -CH2-CH2-C; and NH2 (iv) R can represent neither -NO2 nor -NH2 nor -NH-CHO when R2 NH   is -alk-C, wherein alk is NR'R "C 1 -C 6 alkyl and each of R 'and R" is, independently, hydrogen or methyl,   or an acceptable set for the pharmaceutical use of such a compound.   13. A pharmaceutical composition comprising a carrier and / or diluent acceptable for pharmaceutical use and, as a   active substance, a compound of formula (IA) according to claim   cation 12, wherein, taking into account the restriction (i) of claim 12, n is 0 or a number of 1 to 4; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, R4 represents an unsubstituted or halogen-substituted C1-C4 alkyl group; or b ') -CO (CH 2) m -R 5, where R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, cyclopropyl or a ketone or α-α-unsaturated alkenyl residue, and m is 0 or a number from 1 to 4; or else R 6 b) N, R 6 and R 7 being identical and each representing R 7 is an oxirannemethyl, aziridin-methyl group, or a C 2 -C 4 alkyl group substituted in the 2-position by a halogen or by a group -OSO 2 R 8, in which R 8 is a C1-C4alkyl or phenyl group, or one of the symbols R6 and R7 represents hydrogen and the other has one of the meanings just given; each of R 1 is, independently, hydrogen or C 1 -C 4 alkyl; R2 represents a C 1 -C 6 alkyl group terminated by a basic or acidic unit or by a free or glucosylated hydroxy group,   or a salt acceptable for the pharmaceutical use of such a compound.   14. A pharmaceutical composition according to claim 13, wherein the active substance is a compound of formula (IA) wherein, in accordance with the restriction (i) of claim 12, n is 0, 1 or 2; R represents a) -NHR3, R3 represents: a ') -CON (NO) R4, where R4 represents a C1-C4 alkyl group substituted by a halogen, or b') -CO (CH2) m -R5, where R5 represents a halogen, an oxiranyl, aziridinyl, cyclopropyl or a nsunsaturated alicyclic lactone residue, and m is 0, 1 or 2; or JR6 b) -N, R6 and R7 being identical and representative 7 7   each an oxirane-methyl group, 1-aziridine-   methyl or a C2-C4 alkyl group substituted in the 2-position by a halogen or -OSO2R8 group, wherein R8 is a C1-C4 alkyl group; each of the symbols R 1 represents, independently of the others, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a basic unit, or a group of such a compound and an acid acceptable for pharmaceutical use. 15. A pharmaceutical composition according to claim 14, wherein the basic terminal unit of the substituent R2 of the compound of formula (IA) is selected from amino groups; mono- or CH3   di- (C1-C6) alkylamino; amidino; -N = N-N and the hetero CH3 nitrogenous cycles.   16. A pharmaceutical composition according to claim 13,   in which the active substance is a compound according to   cation 5 or an acceptable salt for the pharmaceutical use of such a compound. 17. A pharmaceutical composition according to claim 16,   wherein the salt is the hydrochloride.   18. A pharmaceutical composition comprising a carrier and / or diluent acceptable for pharmaceutical use and, as a   active substance, a compound of formula (IA) according to claim   12, in which, taking into account restriction (iv) of the claim 12, n is 0 or a number from 1 to 4; R represents   -NO2, -NH2 or -NH-CHO; each of the symbols R 1 represents, independently of the others, hydrogen or a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated by a basic or acidic unit or by a free or glucosylated hydroxy group, or a salt   acceptable for the pharmaceutical use of such a compound.   19. A pharmaceutical composition according to claim 18, wherein the active substance is a compound of formula (IA), wherein: n is 0 or a number of 1 to 4; R represents -NO2, -NH2 or -NH-CHO; each of the symbols R 1 represents, independently, a C 1 -C 4 alkyl group; R2 represents a C1-C6 alkyl group terminated with a substituent selected from amino, mono- and di-C1-C6 alkylamino, CH3-N = N-N and nitrogenous heterocycles; COOH; -CH2-OH; and CH 3 CH 2 -O-D, where D is a sugar or amino sugar residue, or a salt   acceptable for the pharmaceutical use of such a compound. 2 585018   20. A pharmaceutical composition according to claim 18, wherein the active substance is a compound selected from the group consisting of:   3-IN-methyl-4- [N-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2- carboxamido] propyldiméthylamine;   3-IN-methyl-4- [N-methyl-4- [N-methyl-4-nitropyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4-nitropyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2- carboxamido] propyldiméthylamine;   3- [N-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4-   nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamide   mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4- [N-methyl-4-   EN-methyl-4-nitropyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole   2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole 2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-aminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole 2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2- carboxamido] propyldiméthylamine;   3-IN-methyl-4- [N-methyl-4-EN-methyl-4-aminopyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4- [N-methyl-4-   aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl- dimethylamine;   3-IN-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-EN-methyl-4-   [N-methyl-4-aminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole 2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrrole-2-carboxamide   mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyldiméthylamine;   3-IN-methyl-4-EN-methyl-4-EN-methyl-4-EN-methyl-4-formylamino-   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3-EN-methyl-4- [N-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole;   2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl- dimethylamine;   3- [N-methyl-4- [N-methyl-4-EN-methyl-4- [N-methyl-4-EN-methyl-4-   EN-methyl-4-formylaminopyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] -   pyrrole-2-carboxamido] propyldiméthylamine;   3- [N-methyl-4- [N-methyl-4-EN-methyl- (4-formylamino) pyrrole-2   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2-imidazole];   t-EN-methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (2-imidazoline)];   3- [N -methyl-4- [N-methyl-4- [N-methyl-4-formylaminopyrrole-2-carboxamide   mido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (3,4, - 5,6-tetrahydropyrimidine)];   3-IN-methyl-4- [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] ethyl- [2- (4,5-dihydro) oxazole];   t-EN-methyl-4-EN-methyl-4- [N-methyl-4-formylaminopyrrole-2- acid   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propionic acid ,;   alcohol 1-EN-methyl-4- [N-methyl-4-EN-methyl-4-formylaminopyrrole-2-   carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propyl;   1 - [(3-amino-2,3,6-trideoxy-a-L-lyxo-hexapyrannosyl) oxy] trifluoroacetate   3-EN-methyl-4-EN-methyl-4-EN-methyl-4-formylaminopyrrole acetate   2-carboxamido] pyrrole-2-carboxamido] pyrrole-2-carboxamido] propane,   and, where appropriate, their acceptable salts for pharmaceutical use.   tick. 21. A pharmaceutical composition according to claim 20,   in which the salt of the active substance is the hydrochloride.   22. A process for preparing a pharmaceutical composition   as claimed in any one of claims 12 to 24,   which consists in formulating the active substance with a vehicle or di-   Luant acceptable for pharmaceutical use or a mixture thereof.   23. A method according to claim 11 for prepa-   ration of a compound of formula (IA) defined in claim 12.   24. A compound of formula (IA) defined in claim 12, or a salt acceptable for the pharmaceutical use of such a compound, for use as an antiviral and antitumor. 25. A compound or salt according to claim 24, in the form of a pharmaceutical composition according to any one of claims 12 to 21.   26. The use of a compound of formula (IA) defined in claim 12 or an acceptable salt for the pharmaceutical use of such a compound in the preparation of a composition   pharmaceutical composition according to one of claims 12 to 21,   having antiviral and antitumor activity.