JPH0648941A - Curative medicine for erythropenia - Google Patents

Abstract

PURPOSE:To provide curative medicine for erythropenia containing a condensed pyrazole compound as an active ingredient and having action to recover the reduction in red blood cell count caused by marrow transplantation or irradiation with radioactive rays. CONSTITUTION:A compound of formula I {X is N, CH; R is H, alkyl, alkoxy, halogen; Y<1> is formula II, phenyl which may be substituted; Y<2> is formula III, -A<2>-B<2>, H, alkyl, phenylalkyl which may be substituted; alkoxyalkyl, carboxyalkyl; either of Y<1> or Y<2>, or both of them are formula II or formula III [Z<1>, Z<2> are O, S, NR<3> (R<3> is H, alkyl); A<1>, A<2> are alkylene; B<1>, B<2> are H, alkyl, dialkylamino); L<1>, L<2> are H, halogen, alkyl]}, for example, 3-[4-(2- dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4-b]pyridine-1-acetic acid is used as an active ingredient of the objective erythropenia curative medicine.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a medicine, and more particularly to a therapeutic agent for reducing the number of red blood cells.

[0002]

2. Description of the Related Art Erythropoietin, a hematopoietic factor that promotes the production of red blood cells, is mainly used for the treatment of renal anemia. On the other hand, a wide range of hematological disorders caused by bone marrow disorders such as aplastic anemia and myelodysplastic syndrome have been combined with other hematopoietic factors such as granulocyte colony stimulating factor at the same time as bone marrow transplantation. Although it promotes the recovery of the red blood cell count, it has not yet promoted the recovery of the red blood cell count, such as shortening the reduction period of the red blood cell count. On the other hand, Japanese Patent Laid-Open No. 2-8
Japanese Patent No. 5258 discloses a fused pyrazole compound having a leukocyte number recovering ability or a pharmaceutically acceptable salt thereof.

[0003]

For a wide range of hematological disorders (including anemia) caused by bone marrow disorders, it is necessary to transplant a certain number or more of bone marrow cells. Has a limit. Further, in terms of safety, there is a risk that various viruses are mixed in blood and this virus triggers exposure to new infection. In the future, it is desired to develop a drug capable of improving anemia and reducing a blood transfusion amount in a wide field.

[0004]

[Means for Solving the Problems] The inventors of the present invention have conducted diligent research in order to solve the above-mentioned problems.
It was found that the compound disclosed in Japanese Patent No. 5258 and a novel optically active substance thereof promote recovery of red blood cell count, and completed the present invention.

That is, the present invention has the general formula

[0006]

[Chemical 8]

[Wherein, X is ═N— or ═CH—, R represents hydrogen, an alkyl group, an alkoxy group, or halogen, and Y ¹ is a formula:

[0008]

[Chemical 9]

Represents a group represented by phenyl, or phenyl substituted by 1 to 3 halogens, alkyl groups or alkoxy groups. Y ² is the formula:

[0010]

[Chemical 10]

A group represented by the formula: a group represented by the formula: -A ² -B ² , hydrogen, an alkyl group, a phenylalkyl group, and a phenyl nucleus substituted with 1 to 3 halogen, an alkyl group or an alkoxy group. And a phenylalkyl group, a phenyl group or a phenyl group substituted by 1 to 3 halogen, an alkyl group or an alkoxy group, an alkoxyalkyl group, a hydroxyalkyl group, an alkoxycarbonylalkyl group, a carboxyalkyl group and an acyloxyalkyl group. However, of Y ¹ and Y ² ,
Either or both are expressions:

[0012]

[Chemical 11]

Or the formula:

[0014]

[Chemical 12]

Is a group represented by here,
Z ¹ and Z ² are the same or different and each represents —O—, —S— or —NR ³ — (wherein R ³ represents hydrogen or an alkyl group), and A ¹ and A ² are the same or different. Represents an alkylene group, and B ¹ and B ² are the same or different and are a carboxyl group, an alkoxycarbonyl group, a phenylalkoxycarbonyl group (the phenyl may be substituted with 1 to 3 halogen, alkyl group or alkoxy group) , An acyl group, a hydroxyl group, an acyloxy group or a formula:

[0016]

[Chemical 13]

Or

[0018]

[Chemical 14]

(Here, R ¹ and R ² are the same or different and each is hydrogen, an alkyl group, a dialkylaminoalkyl group or a hydroxyalkyl group, or R ¹ and R ² form a heterocycle with the adjacent nitrogen atom. A group represented by L ¹ and L ² are the same or different and each represents hydrogen, halogen, an alkyl group or an alkoxy group. ] A fused pyrazole compound represented by the following formula, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, as an active ingredient.

Furthermore, the present invention provides (+)-3- [4-
(2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or a pharmaceutically acceptable salt thereof as an active ingredient. Regarding therapeutic agents.

In the present specification, the halogen means chlorine, bromine, fluorine or iodine, and the alkyl group has 1 to 1 carbon atoms.
8 straight or branched alkyl, meaning methyl,
Examples thereof include ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, isopentyl and hexyl. The alkoxy group means a linear or branched alkoxy having 1 to 8 carbon atoms, and is methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tertiary butoxy, pentyloxy, isopentyloxy, hexyloxy. And so on. The alkylene group means a linear or branched alkylene having 1 to 8 carbon atoms, methylene, ethylene, 1,1-dimethylethylene, trimethylene, propylene, 2-methyltrimethylene, 2-ethyltrimethylene. , Tetramethylene, pentamethylene, heptamethylene and the like. Phenylalkyl group has 1 carbon atom
~ 4 straight chain or branched alkyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-
Phenylpropyl, 4-phenylbutyl, etc., and 1 to 3 halogen groups on their phenyl rings,
It may be substituted with a linear or branched alkyl group having 1 to 8 carbon atoms or a linear or branched alkoxy group having 1 to 8 carbon atoms. The alkoxyalkyl group is a linear or branched alkoxy or alkyl group having 1 to 4 carbon atoms, and the alkoxy group and the alkyl group are 2-methoxyethyl, 2-ethoxyethyl, 3-
Methoxypropyl, 3-ethoxypropyl, methoxymethyl, 4-ethoxybutyl and the like can be mentioned. The hydroxyalkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, and is 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2-hydroxy-1-. Methyl ethyl, 2,3-dihydroxypropyl and the like can be mentioned.

The alkoxycarbonylalkyl group has an alkoxy group and an alkyl group each having 1 to 4 carbon atoms.
A straight-chain or branched alkoxy and alkyl, such as methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl, 3-ethoxycarbonylpropyl and the like. The carboxyalkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, which is carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3
-Examples include carboxypropyl. The acyloxyalkyl group is a straight-chain or branched alkanoyl having 2 to 5 carbon atoms or benzoyl.
The alkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, and examples thereof include 2-acetyloxyethyl, 3-acetyloxypropyl, 1-benzoyloxymethyl and the like.

The dialkylaminoalkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, each of which is 2-dimethylaminoethyl, 2-diethylaminoethyl, 3-dimethylaminopropyl. , 3-diethylaminopropyl and the like. The alkoxycarbonyl group is a linear or branched alkoxy group having 1 to 4 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and tertiary butoxycarbonyl. Can be given. The phenylalkoxycarbonyl group has an alkoxy group having 1 to 4 carbon atoms.
Linear or branched alkoxy, including benzyloxycarbonyl, 2-phenylethoxycarbonyl,
Examples thereof include 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl and the like. The acyl group is a linear or branched alkanoyl having 2 to 5 carbon atoms (acetyl, propionyl, butyryl, pivaloyl, valeryl etc.) or benzoyl.

The acyloxy group is a straight-chain or branched alkanoyl or benzoyl having 2 to 5 carbon atoms, and examples thereof include acetoxy, propionyloxy, butyryloxy, pivaloyloxy, valeryloxy and benzoyloxy. The heterocycle formed by combining R ¹ and R ² with the adjacent nitrogen atom has at least one nitrogen, oxygen or sulfur which may be substituted with an alkyl group or a hydroxyalkyl group as a hetero atom. 5-7 membered ring which may be
Pyrrolidinyl, piperidino, 1-piperazinyl, 4-methyl-1-piperazinyl, morpholino, thiomorpholino, 4-ethyl-1-piperazinyl, 4- (2-hydroxyethyl) -1-piperazinyl, 1-homopiperazinyl, 4-methyl- 1-homopiperazinyl, 2-oxo-
1-pyrrolidinyl and the like can be mentioned.

Pharmaceutically acceptable salts of the compounds of general formula (I) are hydrochlorides, sulphates, hydrobromides, phosphates, formates, acetates, fumarates, maleates, citrates. Acid salt,
Acid addition salts such as tartrate, malate, mandelate, methanesulfonate, toluenesulfonate, metal salts such as sodium salt, potassium salt, lithium salt, magnesium salt, calcium salt, ammonium salt, triethylamine salt Examples thereof include salts with amino acids such as amine salts (including quaternary ammonium salts), arginine salts, lysine salts, ornithine salts and the like. In addition, hydrates (monohydrate, hemihydrate, 3/2 hydrate, etc.) and other solvates are also included in the present invention.

The compounds of the present invention contained in the general formula (I) include the compounds shown below.

1- [4- (3-Dimethylaminopropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 133-
136 ° C ◎ 3- (4-Bromophenyl) -1- [4- (2-diethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 135-
140 ° C. ◎ 1- [3- (3-Dimethylamino-2-methylpropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 134-
136 ° C. ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1- (4-methylphenyl) -1H-pyrazolo [3,4-b] pyridine maleate, melting point 138-
140 ° C ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylaminopropoxy) phenyl] -1H-indazole maleate, melting point 110-112 ° C

◎ N, N-diethyl-3- [3- (4-
Fluorophenyl) -1H-pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetic acid amide, melting point 102
~ 105 ° C ◎ 1- [4- (2-dimethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 123-126 ° C ◎ 1- [4- (4-Dimethylaminobutoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 112-115 ° C. 1- [4- (2-diethylaminoethoxy) phenyl]- 3-Phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 110-115 ° C. ◎ 1- [4- (3-dimethylamino-2-methylpropoxy) phenyl] -3-phenyl-1H -Pyrazolo [3,4-b] pyridine maleate, melting point 143-
146 ° C

◎ 3- (4-chlorophenyl) -1-
[4- (3-dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine maleate, melting point 162-165 ° C. ◎ 3- (4-bromophenyl) -1- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [ 3,4-b] Pyridine maleate, melting point 162-
165 ° C. ◎ 1- [3- (2-dimethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine dimaleate, melting point 117-120 ° C. ◎ 1- [3- (3-Dimethylaminopropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b]
Pyridine maleate, melting point 120-123 ° C ◎ 1- [3- (2-morpholinoethoxy) phenyl]
-3-Phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 140-142 ° C

◎ 3- (4-chlorophenyl) -1-
[3- (2-dimethylaminoethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine maleate,
Melting point 140-143 ° C ◎ 1- [2- (2-dimethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 153-157 ° C ◎ 1- [ 2- (3-Dimethylaminopropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b]
Pyridine maleate, melting point 123-125 ° C ◎ 3- (4-fluorophenyl) -1- [3- (2-
Piperidinoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 149-
151 ° C. ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate hemihydrate, melting point 102-105 ° C

◎ 3- (4-chlorophenyl) -1-
[3- (3-dimethylamino-2-methylpropoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine
Maleate, melting point 150-152 ° C. 1- [3- (2-diethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate hemihydrate , Melting point 86-90
° C ◎ 3- (4-fluorophenyl) -1- [3- (3-
Piperidinopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, mp 73-75
° C ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylamino-2-methylpropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine maleate hemihydrate, melting point 128 to 130 ° C. ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 110
~ 112 ℃

◎ 3- (4-chlorophenyl) -1-
[3- (3-Dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine fumarate,
Mp 170-172 ° C ◎ 1- [3- (4-dimethylaminobutoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine fumarate monohydrate, mp 140-143 ° C ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1-phenyl-1H-pyrazolo [3,4-b]
Pyridine maleate, melting point 132-135 ° C ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 137- 141 ° C ◎ 4- {3- [3- (4-fluorophenyl) -1H
-Pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetyl} morpholine, melting point 141-143 ° C.

◎ 1- (4-methylphenyl) -3-
[4- (3-dimethylamino-2-methylpropoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine
Maleate, melting point 170-171 ° C ◎ 1-methyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 128-129 ° C. ◎ 6-methyl-1- [3- (3-dimethylamino-2
-Methylpropoxy) phenyl] -3-phenyl-1H
-Pyrazolo [3,4-b] pyridine maleate, melting point 123-125 ° C 1- [3- (3-dimethylamino-2-methylpropoxy) phenyl] -3-phenyl-1H-indazole maleic acid Salt / 2/5 ethyl acetate solvate, melting point 58-
63 ° C. 1- [4- (3-hydroxypropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine, melting point 135-138 ° C.

◎ N- (2-dimethylaminoethyl)-
4- (1-phenyl-1H-pyrazolo [3,4-b] pyridin-3-yl) phenoxyacetic acid amide maleate, melting point 169-171 ° C. N- (2-hydroxyethyl) -3- [3 -(4-
Fluorophenyl) -1H-pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetic acid amide, melting point 161
~ 163 ° C ◎ N- (2-diethylaminoethyl) -3- [3-
(4-Fluorophenyl) -1H-pyrazolo [3,4-
b] pyridin-1-yl) phenoxyacetic acid amide, melting point 137-138 ° C. ◎ 1- {3- [3- (4-fluorophenyl) -1H
-Pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetyl} -4-methylpiperazine, melting point 132-
135 ° C. N- (2-diethylaminoethyl) -4- (1-phenyl-1H-pyrazolo [3,4-b] pyridine-3-
Il) Phenoxyacetic acid amide fumarate, melting point 152
~ 154 ° C

4-methyl-1- [4- (1-phenyl-1H-pyrazolo [3,4-b] pyridin-3-yl) phenoxyacetyl] piperazine maleate,
Mp 187-189 ° C ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 176-177 ° C ◎ 3- [4- (2-dimethylaminoethyl) Amino) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 165 to 167 ° C. ◎ 1-methyl-3- [4- (2-dimethylaminoethylamino) phenyl] -1H-pyrazolo [3,4] -B]
Pyridine maleate, melting point 88-90 ° C ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 1
32-134 ° C

◎ 1- (4-chlorobenzyl) -3-
[4- (3-dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine maleate, melting point 136-138 ° C. ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1- (2-methoxyethyl) -1H-pyrazolo [ 3,4-b] Pyridine maleate, melting point 115-
117 ° C. N, N-dimethyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridin-1-yl acetic acid amide maleate, melting point 165 to 167 ° C. ◎ 1- (2,4-dichlorobenzyl) -3- [4-
(2-Dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 1
36-138 ° C ◎ 1-Butyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 112-113 ° C.

3- [4- (3-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate maleate, melting point 108-
110 ° C. ◎ 1-acetonitrile-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4]
-B] Pyridine maleate, melting point 119 to 121 ° C ◎ 1- (4-fluorophenacyl) -3- [4- (3
-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine / 3/2 fumarate, mp 165-169 ° C 1- (2-chlorobenzyl) -3- [4- (2- Dimethylaminoethylamino) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, mp 155-
157 ° C. ◎ 1- (2-dimethylaminoethyl) -3- [4-
(2-Dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine dimaleate, melting point 96-98 ° C

1- [3- (3-Dimethylaminopropoxy) phenyl] -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridine difumarate, melting point 145 to 148 ° C. ◎ 1- (3-dimethylaminopropyl) -3- [4-
(3-Dimethylaminopropoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine dimaleate, melting point 127-130 ° C ◎ 1- [3- (2-dimethylaminoethoxy) phenyl] -3- [4- (2-dimethylaminoethoxy) phenyl] -1H-Pyrazolo [3,4-b] pyridine difumarate, melting point 115-118 ° C ◎ 1- (4-methylphenyl) -3- [4- (2-dimethylamino-1-methylethoxy) phenyl ] -1H
-Pyrazolo [3,4-b] pyridine maleate, melting point 139-140 ° C ◎ 6-methyl-1- (4-methylphenyl) -3-
[4- (3-dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine

6-Methyl-1- (4-methylphenyl) -3- [4- (3-dimethylamino-2-methylpropoxy) phenyl] -1H-pyrazolo [3,4-b]
Pyridine ◎ 1- (3-methylphenyl) -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine ◎ 1- (3-methylphenyl) -3- [ 4- (3-Dimethylamino-2-methylpropoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine ◎ 1- (2-methylphenyl) -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine ◎ 1- (2-Methylphenyl) -3- [4- (3-dimethylamino-2-methylpropoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine

◎ 1- [3- (2-dimethylamino-1
-Methylethoxy) phenyl] -3-phenyl-1H-
Pyrazolo [3,4-b] pyridine maleate, melting point 118-120 ° C ◎ 2- (4-methylphenyl) -3- [4- (2-dimethylamino-2-methylethoxy) phenyl] -1H
-Pyrazolo [3,4-b] pyridine maleate, melting point 126-128 ° C 1- [3- (2-dimethylamino-2-methylethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,3] 4-b] pyridine-3 / 2 fumarate, melting point 13
9-142 ° C ◎ 3- (4-fluorophenyl) -1- [3- (2-
Dimethylamino-1-methylethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine fumarate, melting point 148-149 ° C ◎ 3- (4-fluorophenyl) -1- [3- (2-
Dimethylamino-2-methylethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine / 3/2 fumarate, mp 174-176 ° C

◎ 3- (4-chlorophenyl) -1-
[3- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, melting point 150-152 ° C ◎ 3- (4-chlorophenyl) -1- [ 3- (2-Dimethylamino-2-methylethoxy) phenyl] -1H
-Pyrazolo [3,4-b] pyridine / 3/2 fumarate, mp 148-150 ° C ◎ 1- [3- (3-dimethylamino-2-methylpropoxy) phenyl] -1-phenyl-1H-pyrazolo [3,4-b] Pyridine maleate salt / 2/5 ethyl acetate solvate, melting point 58-60 ° C ◎ 1- (2-hydroxyethyl) -3- [4- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine.1 / 2 fumarate, melting point 1
62-163 ° C ◎ 1- (2-acetoxyethyl) -3- [4- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, melting point 122-
124 ° C

N-Methyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-ylacetic acid amide difumarate, mp 102-105 ° C ◎ methyl 6- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} hexanoate, NMR (CDCl ₃ ) δ: 1.33
-2.70 (m, 12H), 2.24 (s, 6H), 3.60 (s, 3H), 4.07 (t, 2H),
4.53 (t, 2H), 6.93-8.51 (7H) ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate maleate, Melting point 138-140 ° C. ◎ 4- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} butyrate ethyl difumarate, melting point 121
˜124 ° C. ◎ 3- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} propionate ethyl fumarate, melting point 105-107 ℃

2-Methyl-2- {3- [4- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} propionate ethyl, NMR (CDCl ₃ ) δ: 1.10 (t, 3H), 2.03 (s, 6H), 1.96-
2.40 (m, 2H), 2.30 (s, 6H), 2.52 (t, 2H), 4.01 (t, 2H), 4.
12 (q, 2H), 6.98-8.51 (7H) ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate, NMR (CDCl ₃ ) δ: 1.25 (t, 3H), 1.
33 (d, 3H), 2.33 (s, 6H), 2.34-2.78 (m, 2H), 4.21 (q, 2H),
4.55 (q, 1H), 5.26 (s, 2H), 6.98 to 8.51 (7H) ◎ 4- (1-phenyl-1H-pyrazolo [3,4-
b] Pyridin-3-yl) phenoxyethyl acetate, melting point 118-120 ° C ◎ 4- (1-phenyl-1H-pyrazolo [3,4-
b] Pyridin-3-yl) phenoxyacetic acid, melting point 220
~ 222 ° C ◎ 3- [3- (4-fluorophenyl) -1H-pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetate ethyl, melting point 130-131 ° C.

◎ 3- [3- (4-fluorophenyl)
-1H-Pyrazolo [3,4-b] pyridin-1-yl]
Phenoxyacetic acid, melting point 225-226 ° C ◎ 4- (3-phenyl-1H-pyrazolo [3,4-
b] Pyridin-1-yl) phenoxyethyl acetate ◎ 4- (3-phenyl-1H-pyrazolo [3,4-
b] pyridin-1-yl) phenoxyacetic acid ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1-propionyl-1H-pyrazolo [3,4-
b] Pyridine / 3/2 fumarate, melting point 155-157
° C ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-
Acetic acid, melting point 221-223 ° C

◎ 3- [4- (3-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid, melting point 221-223 ° C ◎ 3- [4- (2-dimethyl Amino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 130-132 ° C ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate NMR (CDCl ₃ ) δ: 1.25 (t, 3H), 1.33 (d, 3H), 2.33 (s, 6H),
2.34-2.78 (m, 2H), 4.21 (q, 2H), 4.55 (q, 1H), 5.26 (s, 2
H), 6.98 to 8.51 (7H) ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid, melting point 210-211 ° C. ◎ 2-methyl-2- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridin-1-yl} propionic acid, melting point 187-
190 ° C

3- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridin-1-yl} propionic acid hemihydrate, melting point 86 to 90 ° C. ◎ 6- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4- b] pyridin-1-yl} hexanoic acid, melting point 96 to 100 ° C. ◎ 3- [4- (2-dimethylaminoethylamino) phenyl] -1H-pyrazolo [3,4-b] pyridine-1
-Acetic acid NMR (CDCl ₃ ) δ: 1.20 (t, 3H), 2.40 (s, 6H), 2.56 (t, 2H),
3.20 (t, 2H), 4.20 (q, 2H), 5.30 (s, 2H), 6.63 to 8.56 (7H) ◎ 3- [4- (2-dimethylaminoethylamino) phenyl] -1H-pyrazolo [3. 4-b] pyridine-1
-Acetic acid, melting point 240-242 ° C ◎ 3-phenyl-1- (4-trifluoroacetylaminophenyl) -1H-pyrazolo [3,4-b] pyridine, melting point 172-174 ° C.

1- [4- (2-dimethylaminoethylamino) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate hemihydrate, melting point 80- 88 ° C ◎ 1- [4- (3-dimethylaminopropylamino)
Phenyl] -3-phenyl-1H-pyrazolo [3,4-
b] Pyridine dimaleate, melting point 145-146 ° C

In the general formula (I), a compound in which X is ═N— and / or at least one of Z ¹ and Z ² is oxygen is preferable. The following compounds are exemplified as more preferable compounds of the compound of the general formula (I) and pharmaceutically acceptable salts thereof.

◎ 3- [4- (2-dimethylamino-1
-Methylethoxy) phenyl] -1H-pyrazolo [3,3
4-b] pyridine-1-acetic acid, ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate, ◎ 3- [4- (3-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-
Acetic acid, ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate, ◎ 1- [4- (3-dimethylaminopropoxy) phenyl] -3-Phenyl-1H-pyrazolo [3,4-b]
Pyridine,

◎ 1- [3- (3-dimethylamino-2
-Methylpropoxy) phenyl] -3-phenyl-1H
-Pyrazolo [3,4-b] pyridine, ◎ 1- (4-methylphenyl) -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, ◎ 1 -[3- (2-Dimethylaminoethoxy) phenyl] -3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, ◎ N- (2-diethylaminoethyl) -3- [3-
(4-Fluorophenyl) -1H-pyrazolo [3,4-
b] pyridin-1-yl] phenoxyacetic acid amide and ◎ 3- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} propionic acid and Its optical isomer,
Or a pharmaceutically acceptable salt thereof.

Most of the compounds used in the present invention are produced by the method described in JP-A-2-85258, which is incorporated herein by reference. Also,
The optical isomer can be obtained by using an optically active raw material or optically resolving the obtained racemate. In order to achieve the object of the present invention, the active ingredient compound,
3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester, their optically active substances or their pharmaceutically acceptable Possible salts are preferred.

Further, as an optically active compound of the compound (I) for achieving the object of the present invention, (+)-3- [4-
(2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or their pharmaceutically acceptable salts. These optically active substances can be produced by the following methods. That is, Japanese Patent Publication No. Sho 49-19
No. 252, optically active (+)-1-dimethylamino-2-propanol and, for example, 2-chloro-3- (4-fluorobenzoyl) pyridine are added to benzene, toluene, xylene, pyridine, ethanol, isopropyl alcohol. , Ethylene glycol dimethyl ether, dimethylformamide, in a solvent inert to the reaction such as dioxane, sodium hydroxide, sodium hydride, potassium hydride, sodium hydrogen carbonate, if necessary,
By using a deoxidizing agent such as sodium carbonate, potassium carbonate or triethylamine to react at a temperature of 0 to 250 ° C, (+)-2-chloro-3- [4- (2-dimethylamino-1-methylethoxy) Benzoyl] pyridine, and then reflux the above compound and hydrazine in a suitable solvent such as benzene, toluene, xylene, dioxane, diethylene glycol dimethyl ether, pyridine, etc., using a suitable dehydrating agent or deoxidizing agent as necessary. (+)-3- [4- (2-dimethylamino-1)
-Methylethoxy) phenyl] -1H-pyrazolo [3,3
4-b] Pyridine is obtained. The obtained pyrazolo [3,
4-b] a pyridine compound and ethyl chloroacetate in a solvent inert to the reaction such as benzene, toluene, xylene, dimethylformamide, pyridine, chloroform, dichloromethane, dichloroethane, methanol, and ethanol, if necessary, sodium hydroxide, By using a deoxidizing agent such as potassium hydroxide, sodium hydride, potassium hydride, sodium carbonate, potassium carbonate or triethylamine at a temperature of 0 to 250 ° C.,
(+)-3- [4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b]
Pyridine-1-ethyl acetate is obtained. Further, the ethyl acetate compound is hydrolyzed in the presence of an acid or an alkali to give (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4]. -B] Pyridine-1-acetic acid. (+)-3- [4- (2-
Dimethylamino-1-methylethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester include hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, formic acid, acetic acid, fumaric acid, maleic acid, citric acid, tartaric acid, malic acid, The corresponding acid addition salt can be obtained by treating the organic acid with an inorganic acid such as mandelic acid, methanesulfonic acid, or toluenesulfonic acid by a conventional method. In producing the medicament of the present invention, the compound is preferably contained in a therapeutically effective amount, and the medicament contains, in addition to these active ingredients, a pharmaceutically acceptable carrier, excipient, diluent, It can be safely orally or parenterally administered to a patient by mixing with a solubilizing agent, a disintegrating agent, a binder and the like to prepare tablets, powders, capsules, injections, suppositories, drops, etc. . The dose is usually 2.5 to 100 mg by oral administration and 0.5 to 20 mg by intravenous administration to an adult per day. In particular, (+)-3- [4
-(2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid ethyl ester has a good absorption rate by oral administration and is excellent in bioavailability. Therefore, it can be applied as an oral preparation.

[0053]

ACTION AND EFFECT OF THE INVENTION The compound of the general formula (I) has an action to restore the number of red blood cells. Therefore, the drug of the present invention is useful as a drug for promoting the reduction of the number of red blood cells by bone marrow transplantation, anti-cancer agent or irradiation. Is. Alternatively, it is used for treatment of aplastic anemia, congenital anemia, renal anemia, myeloid anemia and the like.

[0054]

EXAMPLES The present invention will be described in more detail with reference to production examples, pharmaceutical formulation examples and experimental examples, but it goes without saying that the present invention is not limited thereto.

Production Example 1 (1) 60 ml of sodium hydride 60% in 150 ml of toluene
7 g is suspended, and a mixed liquid of 200 ml of toluene containing 75 g of (+)-1-dimethylamino-2-propanol is added to 50-
Add dropwise at 60 ° C. This was cooled, 200 ml of dimethylformamide was added, and 2-chloro-3 was added at -10 to -5 ° C.
182 g of-(4-fluorobenzoyl) pyridine is added in several times. It takes 3 hours and the temperature gradually increases to 40 ° C.
The reaction is completed by raising the temperature to 40 ° C. and further heating and stirring at 40 ° C. for 2 hours. Water is added, the toluene layer is separated and washed with water. The toluene layer is extracted with diluted hydrochloric acid.
The extract is made alkaline with potassium carbonate and the liberated oil is extracted with toluene. If toluene is distilled off, crude 2-chloro-3- [4- (2-dimethylamino-1-
190 g of methylethoxy) benzoyl] pyridine are obtained as an oil.

(2) 190 g of the above crude product, 60 pyridine
0 ml and 92 g of hydrazine hydrate are refluxed and stirred for 12 hours. Pyridine was distilled off, and toluene 5 was added to the residue.
Add 00 ml and heat to 40-50 ° C. to dissolve.
Wash with warm water and evaporate toluene. The residue was crystallized by adding isopropyl ether, filtered, and recrystallized from a mixed solution of isopropyl ether and isopropyl alcohol to give (+)-3- [4-
(2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine 100.
7 g are obtained. [Α] _D ²³ = + 15.3 ° (1%, methanol)

(3) 2.7 g of 60% sodium hydride was suspended in 46 ml of toluene, 31 ml of dimethylformamide was added under ice cooling, and then (+)-3- [4- (2
-Dimethylamino-1-methylethoxy) phenyl]-
18 g of 1H-pyrazolo [3,4-b] pyridine was added to 2-3
Put in dividedly. After stirring for 15 minutes, a mixed solution of 8.2 g of ethyl chloroacetate and 16 ml of toluene was added dropwise, and the mixture was reacted at room temperature for 1 hour and at 40 ° C. for 1 hour. After cooling, water is added and the toluene layer is collected, washed with water and dried. If toluene is distilled off, crude (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate 20. 8 g are obtained as an oil.

(4) Crude (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H
-Pyrazolo [3,4-b] pyridine-1-ethyl acetate 2
0.8 g is dissolved in 150 ml of ethyl acetate, and 13 g of 15% hydrochloric acid-ethanol solution is added to give a hydrochloride. The produced crystals were purified by a mixed solution of ethyl acetate-ethanol to give (+)-3- [4- (2-
Dimethylamino-1-methylethoxy) phenyl] -1
17.2 g of H-pyrazolo [3,4-b] pyridine-1-ethyl acetate / hydrochloride is obtained. [Α] _D ²⁵ = + 16.1 °
(1%, ethanol)

Production Example 2 20.8 g of the crude product of the above Production Example 1 (3) was added to methanol 4
Dissolved in 3 ml, sodium hydroxide 2.4 g, water 21 m
1 solution is added and stirred at room temperature for 1 hour. P with diluted hydrochloric acid
After adjusting to H7 and distilling off methanol, the residue is purified using DIAION PH-20. After being recrystallized from water-containing isopropyl alcohol (including water of crystallization), ethanol was added and heated to obtain (+)-3 with a melting point of 212 to 213 ° C.
-[4- (2-Dimethylamino-1-methylethoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine-
1-acetic acid is obtained. [Α] _D ²² = + 25.7 ° (1%, methanol)

Production Example 3 (1) When (-)-1-dimethylamino-2-propanol was used to carry out the reaction treatment in the same manner as in Production Example 1 (1) and (2), a melting point of 125-127 ° C. -)-3- [4- (2
-Dimethylamino-1-methylethoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine is obtained. [Α]
_D ²³ = -15.0 ° (1%, methanol)

(2) Using (-)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, (3) of Production Example 1
If the reaction treatment is performed in the same manner as in Example 2, the melting point of 212 to
(-)-3- [4- (2-dimethylamino-
1-Methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid is obtained. [Α] _D ²³
= -25.0 ° (1%, methanol)

In the following formulation examples and experimental examples, compound A, compound B and compound C are as follows.

Compound A = (±) -3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine-1-acetic acid

Compound B = (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine-1-acetic acid

Compound C = (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine-1-ethyl acetate / hydrochloride

Formulation Example 1

10 g of compound A and 9 g of sodium chloride
Is dissolved in 10 liters of water for injection, and after sterile filtration, 10 m
Take l, fill an ampoule, seal, and sterilize under high pressure steam to obtain an injection.

Formulation Example 2

An injection containing Compound B is produced in the same manner as in Production Formulation Example 1 using Compound B.

Formulation formulation example 3

Compound C (50 mg) is sufficiently kneaded with lactose (98 mg), corn starch (45 mg) and hydroxypropyl cellulose (3 mg) in a kneader. 200 kneaded products
Pass through a mesh screen, dry at 50 ° C, and then pass through a 24 mesh screen. Mix with 3 mg of talc and 1 mg of magnesium stearate and obtain a tablet with a weight of 200 mg using a 9 mm diameter punch. The tablets can be sugar-coated or film-coated, if necessary.

Experimental Example 1: Recovery promoting effect of red blood cell count in X-irradiated mice (preventive effect)

4.0 to 4-5 week old BALB / c mice
Whole-body irradiation with Gy was performed. Compound A was intravenously administered for 3 consecutive days from 3 days before X-ray irradiation to the day before. On the 19th and 22nd days after X-ray irradiation, blood was collected from the mouse orbital venous plexus and the red blood cell count was measured by an automatic hemocytometer. Experiment 1
A group of 8 animals was used, and the results are shown as mean value ± standard deviation.

[0074]

[Table 1] Table 1 ──────────────────────────────────── Treatment Subject Dose Red blood cell count (10 ⁴ / mm ³ ) (mg / kg) Day 19 Day 22 ─────────────────────────────────── ── X-ray irradiation − 0 506 ± 175 696 ± 192 X-ray irradiation Compound A 0.01 835 ± 102 904 ± 45 X-ray irradiation Compound A 0.1 837 ± 118 916 ± 86 X-ray irradiation Compound A 1 856 ± 118 932 ± 86 None Treatment-0 1021 ± 75 994 ± 43 ─────────────────────────────────────

As is clear from Table 1, it was found that administration of compound A to X-ray-irradiated mice promoted recovery of erythrocyte counts to almost normal levels.

Experimental Example 2: Effect of promoting recovery of red blood cell count in X-irradiated mice (therapeutic effect)

4.0 to 4-5 week old BALB / c mice
Whole-body irradiation with Gy was performed. Compound A was intravenously administered for 9 consecutive days from the day after the X-ray irradiation to the 9th day. On the 14th day after the X-ray irradiation, blood was collected from the mouse orbital venous plexus and the red blood cell count was measured by an automatic hemocytometer. The experiment was conducted with 6 animals per group, and the results are shown as the average value ± standard deviation.

[0078]

[Table 2] Table 2 ──────────────────────────────────── Treatment Subject Dose Red blood cell count (mg / Kg) (10 ⁴ / mm ³ ) ──────────────────────────────────── X-ray irradiation − 0 327 ± 121 X-ray irradiation Compound A 0.01 535 ± 98 X-ray irradiation Compound A 0.1 686 ± 72 No treatment − 0 939 ± 69 ───────────────────── ───────────────

As is clear from Table 2, it was found that when compound A was administered to X-ray-irradiated mice, the number of red blood cells recovered to almost normal level.

Experimental Example 3: Recovery of erythrocyte count in bone marrow transplanted mice

Six to eight-week-old ICR mice were whole-body irradiated with 8.0 Gy of radiation and then transplanted with 10 ⁷ syngeneic mouse bone marrow cells. Compound A was intravenously administered for 9 consecutive days from the day after bone marrow transplantation. On the 11th day after bone marrow transplantation, heparinized blood was collected from the mouse abdominal aorta and the number of red blood cells was measured by an automatic hemocytometer. The experiment was conducted with 5 animals per group.

[0082]

[Table 3] Table 3 ─────────────────────────────────── Pretreatment Subject Dose Red blood cell count (mg / Kg) (10 ⁴ / mm ³ ) ──────────────────────────────────── X-ray irradiation only- 0 550 ± 119 X-ray irradiation + bone marrow transplant − 0 637 ± 40 X-ray irradiation + bone marrow transplant Compound A 0.01 699 ± 51 X-ray irradiation + bone marrow transplant Compound A 0.1 714 ± 56 No treatment − 0 722 ± 105 ──── ───────────────────────────────

As is clear from Table 3, when compound A was administered to bone marrow-transplanted mice, it was found that the number of red blood cells returned to almost normal level.

As is clear from the above experimental examples, administration of compound A to X-ray-irradiated or bone marrow transplanted animals accelerates recovery of the decrease in red blood cell count.

Experimental Example 4: Acute toxicity experiment

When Compound A, Compound B and Compound C were orally administered to rats, each dose was 1000 mg / kg.
No cases of death were observed.

Claims (2)

[Claims] 1. A general formula: [In the formula, X is = N- or = CH-, R is hydrogen,
Represents an alkyl group, an alkoxy group, or halogen, and Y ¹ is represented by the formula: Represents a group represented by, a phenyl group, or a phenyl group substituted with 1 to 3 halogen, an alkyl group or an alkoxy group. Y ² has the formula: A group represented by the formula: a group represented by -A ² -B ^2, hydrogen, alkyl group, phenyl group, 1-phenyl nucleus is halogen, alkyl or alkoxy group
1 of phenylalkyl group, phenyl group or halogen, alkyl group or alkoxy group substituted by 3
It shows a phenyl group, an alkoxyalkyl group, a hydroxyalkyl group, an alkoxycarbonylalkyl group, a carboxyalkyl group, and an acyloxyalkyl group substituted by 3 to 3. However, ^one of Y ¹ and Y ²
Or both have the formula: Or the formula: Is a group represented by. Here, Z ¹ and Z ² are the same or different and are —O—, —S— or —NR ³ —.
(Wherein R ³ represents hydrogen or an alkyl group), A ¹ and A ² are the same or different and represent an alkylene group, and B ¹ and B ² are the same or different and a carboxyl group,
Alkoxycarbonyl group, phenylalkoxycarbonyl group (the phenyl may be substituted by 1 to 3 of halogen, alkyl group or alkoxy group), acyl group, hydroxyl group, acyloxy group or the formula: Or [Chemical 7] (Here, R ¹ and R ² are the same or different and each is hydrogen, an alkyl group, a dialkylaminoalkyl group, a hydroxyalkyl group, or a group in which R ¹ and R ² form a heterocycle with the adjacent nitrogen atom. Represents a group represented by. L ¹ and L ² are the same or different and each represents hydrogen, halogen, an alkyl group or an alkoxy group. ] A condensed pyrazole compound represented by the following, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient, a therapeutic agent for erythopenia. 2. (+)-3- [4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or their An agent for treating leukopenia, which comprises a pharmaceutically acceptable salt as an active ingredient.