NO300267B1 - Akridin-derivater, samt anvendelse av slike i farmasöytiske preparater - Google Patents

Akridin-derivater, samt anvendelse av slike i farmasöytiske preparater Download PDF

Info

Publication number: NO300267B1
Authority: NO; Norway
Prior art keywords: dihydro; oxo; methyl; acridinecarboxamide; phenyl
Prior art date: 1991-01-11

Application number

NO932512A

Other languages

English (en)

Norwegian (no)

Other versions

NO932512L (no

NO932512D0 (no

Inventor

Bernard Andre Dumaitre

Nerina Dodic

Original Assignee

Glaxo Lab Sa

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-01-11

Filing date

1993-07-09

Publication date

1997-05-05

1991-01-11 Priority claimed from GB919100628A external-priority patent/GB9100628D0/en

1991-01-11 Priority claimed from GB919100637A external-priority patent/GB9100637D0/en

1991-07-24 Priority claimed from GB919115981A external-priority patent/GB9115981D0/en

1991-07-24 Priority claimed from GB919115956A external-priority patent/GB9115956D0/en

1993-07-09 Application filed by Glaxo Lab Sa filed Critical Glaxo Lab Sa

1993-07-09 Publication of NO932512D0 publication Critical patent/NO932512D0/no

1993-09-09 Publication of NO932512L publication Critical patent/NO932512L/no

1997-05-05 Publication of NO300267B1 publication Critical patent/NO300267B1/no

Links

239000000825 pharmaceutical preparation Substances 0.000 title claims description 7
229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 title description 2
125000000641 acridinyl group Chemical class C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 411
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 96
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 46
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 43
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
239000001257 hydrogen Substances 0.000 claims abstract description 42
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 29
239000002246 antineoplastic agent Substances 0.000 claims abstract description 23
229940041181 antineoplastic drug Drugs 0.000 claims abstract description 20
239000012453 solvate Substances 0.000 claims abstract description 20
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 15
229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
239000001301 oxygen Substances 0.000 claims abstract description 13
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
125000005843 halogen group Chemical group 0.000 claims abstract description 9
229910052799 carbon Inorganic materials 0.000 claims abstract description 5
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 49
206010028980 Neoplasm Diseases 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 13
125000004434 sulfur atom Chemical group 0.000 claims description 11
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
201000011510 cancer Diseases 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 8
GDALETGZDYOOGB-UHFFFAOYSA-N Acridone Natural products C1=C(O)C=C2N(C)C3=CC=CC=C3C(=O)C2=C1O GDALETGZDYOOGB-UHFFFAOYSA-N 0.000 claims description 7
FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical group C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 claims description 7
229940079593 drug Drugs 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
FXKRMUXJZJIWHJ-UHFFFAOYSA-N n-[4-[2-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]ethyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=CC=CC=C1C2=O FXKRMUXJZJIWHJ-UHFFFAOYSA-N 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
230000035945 sensitivity Effects 0.000 claims description 3
108010092160 Dactinomycin Proteins 0.000 claims description 2
108010026389 Gramicidin Proteins 0.000 claims description 2
229930012538 Paclitaxel Natural products 0.000 claims description 2
206010034133 Pathogen resistance Diseases 0.000 claims description 2
229940122803 Vinca alkaloid Drugs 0.000 claims description 2
229930183665 actinomycin Natural products 0.000 claims description 2
125000004450 alkenylene group Chemical group 0.000 claims description 2
229940045799 anthracyclines and related substance Drugs 0.000 claims description 2
150000003857 carboxamides Chemical group 0.000 claims description 2
239000000969 carrier Substances 0.000 claims description 2
NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 claims description 2
229960001338 colchicine Drugs 0.000 claims description 2
229960001156 mitoxantrone Drugs 0.000 claims description 2
KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 2
BJRLHOPOAYFBCU-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethoxy]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC=C3N=C12 BJRLHOPOAYFBCU-UHFFFAOYSA-N 0.000 claims description 2
RRHUXEZDYUVVEE-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethyl]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC(F)=C3N=C12 RRHUXEZDYUVVEE-UHFFFAOYSA-N 0.000 claims description 2
DLWIITOABJLWFP-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethyl]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC(OC)=C3N=C12 DLWIITOABJLWFP-UHFFFAOYSA-N 0.000 claims description 2
OACMSNYSFQHHBC-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethyl]phenyl]-5-methyl-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC(C)=C3N=C12 OACMSNYSFQHHBC-UHFFFAOYSA-N 0.000 claims description 2
RTBHPFCZGNWMGJ-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethyl]phenyl]-5-methylsulfanyl-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(SC)C=CC=C1C2=O RTBHPFCZGNWMGJ-UHFFFAOYSA-N 0.000 claims description 2
FPMXYOPUARQMFH-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC=C3N=C12 FPMXYOPUARQMFH-UHFFFAOYSA-N 0.000 claims description 2
LTUYECVTMBHVKK-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethylamino]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCNC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(OC)C=CC=C1C2=O LTUYECVTMBHVKK-UHFFFAOYSA-N 0.000 claims description 2
GCHGWNGCLDANFD-UHFFFAOYSA-N n-[4-[2-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]ethoxy]phenyl]-2-methylsulfanyl-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCOC(C=C1)=CC=C1NC(=O)C1=CC(SC)=CC2=C1NC1=CC=CC=C1C2=O GCHGWNGCLDANFD-UHFFFAOYSA-N 0.000 claims description 2
PYOKHQLGUVPBOC-UHFFFAOYSA-N n-[4-[2-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]ethoxy]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(OC)C=CC=C1C2=O PYOKHQLGUVPBOC-UHFFFAOYSA-N 0.000 claims description 2
IDNRPUOUMVJOPY-UHFFFAOYSA-N n-[4-[2-[2-(4-methoxyphenyl)ethyl-methylamino]ethoxy]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CCN(C)CCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=CC=CC=C1C2=O IDNRPUOUMVJOPY-UHFFFAOYSA-N 0.000 claims description 2
ZQTOFLDTSRFUPD-UHFFFAOYSA-N n-[4-[2-[2-(4-methoxyphenyl)ethyl-methylamino]ethyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CCN(C)CCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=CC=CC=C1C2=O ZQTOFLDTSRFUPD-UHFFFAOYSA-N 0.000 claims description 2
CCIHTZLJRXHQGS-UHFFFAOYSA-N n-[4-[3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)propyl]-2-methoxyphenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(OC)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(CCCN3CC4=CC(OC)=C(OC)C=C4CC3)C=C1OC)=CC=C2 CCIHTZLJRXHQGS-UHFFFAOYSA-N 0.000 claims description 2
IVKDSAVYYOSGKS-UHFFFAOYSA-N n-[4-[3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)propyl]-2-methoxyphenyl]-5-methyl-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(C)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(CCCN3CC4=CC(OC)=C(OC)C=C4CC3)C=C1OC)=CC=C2 IVKDSAVYYOSGKS-UHFFFAOYSA-N 0.000 claims description 2
JQJXQDGRTYGSLZ-UHFFFAOYSA-N n-[4-[3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)propylsulfanyl]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(OC)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(C=C1)SCCCN1CCC=3C=C(C(=CC=3C1)OC)OC)=CC=C2 JQJXQDGRTYGSLZ-UHFFFAOYSA-N 0.000 claims description 2
PDRZEJQPKYJNPH-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propoxy]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(F)C=CC=C1C2=O PDRZEJQPKYJNPH-UHFFFAOYSA-N 0.000 claims description 2
FHBXLEMVHRZVJX-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propoxy]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(OC)C=CC=C1C2=O FHBXLEMVHRZVJX-UHFFFAOYSA-N 0.000 claims description 2
DTQFYQCJCBYDQS-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propoxy]phenyl]-5-methyl-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(C)C=CC=C1C2=O DTQFYQCJCBYDQS-UHFFFAOYSA-N 0.000 claims description 2
OBCREAQUUKLQDV-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propoxy]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC=C3N=C12 OBCREAQUUKLQDV-UHFFFAOYSA-N 0.000 claims description 2
BSQIXBSTVWCXFK-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propyl]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(F)C=CC=C1C2=O BSQIXBSTVWCXFK-UHFFFAOYSA-N 0.000 claims description 2
QNYLQNICJRJDCO-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC=C3N=C12 QNYLQNICJRJDCO-UHFFFAOYSA-N 0.000 claims description 2
KQYMVYABXUESOR-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propylsulfanyl]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCSC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(F)C=CC=C1C2=O KQYMVYABXUESOR-UHFFFAOYSA-N 0.000 claims description 2
XFKAFKDZNFWLRZ-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propylsulfanyl]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCSC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(OC)C=CC=C1C2=O XFKAFKDZNFWLRZ-UHFFFAOYSA-N 0.000 claims description 2
OLEFMMCBNLBWBA-UHFFFAOYSA-N n-[4-[3-[(3,4-dimethoxyphenyl)methyl-methylamino]propylsulfanyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCSC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC=C3N=C12 OLEFMMCBNLBWBA-UHFFFAOYSA-N 0.000 claims description 2
WFMWSXDUMHIYFS-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propoxy]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCOC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=CC=CC=C1C2=O WFMWSXDUMHIYFS-UHFFFAOYSA-N 0.000 claims description 2
RUITTZMAJZJJQN-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=CC=CC=C1C2=O RUITTZMAJZJJQN-UHFFFAOYSA-N 0.000 claims description 2
RKAXEYPONMPHMA-UHFFFAOYSA-N n-[4-[4-[(3,4-dimethoxyphenyl)methyl-methylamino]butyl]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(F)C=CC=C1C2=O RKAXEYPONMPHMA-UHFFFAOYSA-N 0.000 claims description 2
PGZKMUKWKCKXBE-UHFFFAOYSA-N n-[4-[4-[(3,4-dimethoxyphenyl)methyl-methylamino]butyl]phenyl]-5-methoxy-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(OC)C=CC=C1C2=O PGZKMUKWKCKXBE-UHFFFAOYSA-N 0.000 claims description 2
SVIYPTJHZNDZSV-UHFFFAOYSA-N n-[4-[4-[(3,4-dimethoxyphenyl)methyl-methylamino]butyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C(O)C3=CC=CC=C3N=C12 SVIYPTJHZNDZSV-UHFFFAOYSA-N 0.000 claims description 2
DJXZBZWPALKJDL-UHFFFAOYSA-N n-[4-[5-[(3,4-dimethoxyphenyl)methyl-methylamino]pentyl]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCCCCC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=C(F)C=CC=C1C2=O DJXZBZWPALKJDL-UHFFFAOYSA-N 0.000 claims description 2
229960001592 paclitaxel Drugs 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 2
XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims 1
229960001220 amsacrine Drugs 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
MYBOWAAJDSSBCZ-UHFFFAOYSA-N n-[4-[2-[(3,4-dimethoxyphenyl)methyl-methylamino]ethylsulfanyl]phenyl]-9-oxo-10h-acridine-4-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CN(C)CCSC(C=C1)=CC=C1NC(=O)C1=CC=CC2=C1NC1=CC=CC=C1C2=O MYBOWAAJDSSBCZ-UHFFFAOYSA-N 0.000 claims 1
YFCQFJMHPGREIJ-UHFFFAOYSA-N n-[4-[3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)propylsulfanyl]phenyl]-5-fluoro-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(F)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(C=C1)SCCCN1CCC=3C=C(C(=CC=3C1)OC)OC)=CC=C2 YFCQFJMHPGREIJ-UHFFFAOYSA-N 0.000 claims 1
XWGBKRZERPPWNF-UHFFFAOYSA-N n-[4-[3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)propylsulfanyl]phenyl]-5-methyl-9-oxo-10h-acridine-4-carboxamide Chemical compound N1C2=C(C)C=CC=C2C(=O)C2=C1C(C(=O)NC1=CC=C(C=C1)SCCCN1CCC=3C=C(C(=CC=3C1)OC)OC)=CC=C2 XWGBKRZERPPWNF-UHFFFAOYSA-N 0.000 claims 1
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229940127089 cytotoxic agent Drugs 0.000 abstract description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 3
208000016691 refractory malignant neoplasm Diseases 0.000 abstract description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
238000002560 therapeutic procedure Methods 0.000 abstract 1
239000000543 intermediate Substances 0.000 description 386
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 326
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 265
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RERFVRJAYHESMP-UHFFFAOYSA-N n-benzyl-n-ethyl-2-(4-nitrophenoxy)acetamide Chemical compound C=1C=C([N+]([O-])=O)C=CC=1OCC(=O)N(CC)CC1=CC=CC=C1 RERFVRJAYHESMP-UHFFFAOYSA-N 0.000 description 1
FHCASHGVHQFHML-UHFFFAOYSA-N n-benzyl-n-methyl-2-(4-nitrophenoxy)acetamide Chemical compound C=1C=C([N+]([O-])=O)C=CC=1OCC(=O)N(C)CC1=CC=CC=C1 FHCASHGVHQFHML-UHFFFAOYSA-N 0.000 description 1
HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 description 1
LFULMNRPABTDDQ-UHFFFAOYSA-N n-methyl-1-(3,4,5-trimethoxyphenyl)methanamine Chemical compound CNCC1=CC(OC)=C(OC)C(OC)=C1 LFULMNRPABTDDQ-UHFFFAOYSA-N 0.000 description 1
YDFFIGRIWDSNOZ-UHFFFAOYSA-N n-methyl-1-(4-methylphenyl)methanamine Chemical compound CNCC1=CC=C(C)C=C1 YDFFIGRIWDSNOZ-UHFFFAOYSA-N 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
MLHBZVFOTDJTPK-UHFFFAOYSA-N n-methyl-3-phenylpropan-1-amine Chemical compound CNCCCC1=CC=CC=C1 MLHBZVFOTDJTPK-UHFFFAOYSA-N 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
229960001783 nicardipine Drugs 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000012071 phase Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical group CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
229960001404 quinidine Drugs 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
230000001235 sensitizing effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910001961 silver nitrate Inorganic materials 0.000 description 1
AYKOTYRPPUMHMT-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag] AYKOTYRPPUMHMT-UHFFFAOYSA-N 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
229960002066 vinorelbine Drugs 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/07—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms
- C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/26—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups and being further substituted by halogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/36—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- C07C205/37—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/06—Oxygen atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Plural Heterocyclic Compounds (AREA)
Laminated Bodies (AREA)
Soft Magnetic Materials (AREA)
Paper (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Dry Shavers And Clippers (AREA)

NO932512A 1991-01-11 1993-07-09 Akridin-derivater, samt anvendelse av slike i farmasöytiske preparater NO300267B1 (no)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB919100628A GB9100628D0 (en)	1991-01-11	1991-01-11	Chemical compounds
GB919100637A GB9100637D0 (en)	1991-01-11	1991-01-11	Chemical compounds
GB919115981A GB9115981D0 (en)	1991-07-24	1991-07-24	Chemical compounds
GB919115956A GB9115956D0 (en)	1991-07-24	1991-07-24	Chemical compounds
PCT/EP1992/000020 WO1992012132A1 (en)	1991-01-11	1992-01-07	Acridine derivatives

Publications (3)

Publication Number	Publication Date
NO932512D0 NO932512D0 (no)	1993-07-09
NO932512L NO932512L (no)	1993-09-09
NO300267B1 true NO300267B1 (no)	1997-05-05

Family

ID=27450605

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO932512A NO300267B1 (no)	1991-01-11	1993-07-09	Akridin-derivater, samt anvendelse av slike i farmasöytiske preparater

Country Status (25)

Country	Link
US (1)	US5604237A (sk)
EP (2)	EP0494623A1 (sk)
JP (1)	JP2783680B2 (sk)
KR (1)	KR100220538B1 (sk)
AT (1)	ATE153660T1 (sk)
AU (1)	AU652996B2 (sk)
CA (1)	CA2100258C (sk)
CZ (1)	CZ283038B6 (sk)
DE (1)	DE69220037T2 (sk)
DK (1)	DK0569380T3 (sk)
ES (1)	ES2104887T3 (sk)
FI (1)	FI103888B (sk)
GE (1)	GEP20002210B (sk)
GR (1)	GR3024525T3 (sk)
HU (2)	HUT68856A (sk)
IE (1)	IE920083A1 (sk)
IL (1)	IL100631A (sk)
MX (1)	MX9200109A (sk)
NO (1)	NO300267B1 (sk)
NZ (1)	NZ241278A (sk)
PL (1)	PL168202B1 (sk)
RU (1)	RU2119482C1 (sk)
SG (1)	SG45403A1 (sk)
SK (1)	SK280864B6 (sk)
WO (1)	WO1992012132A1 (sk)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU652996B2 (en) *	1991-01-11	1994-09-15	Laboratoires Glaxo S.A.	Acridine derivatives
TR28930A (tr) *	1992-05-07	1997-07-21	Zeneca Ltd	Alkil sübstitüentli nitrotoluen türevleri
GB9209872D0 (en) *	1992-05-07	1992-06-24	Ici Plc	Alkyl substituted nitrotoluene derivatives
JP2718830B2 (ja) *	1992-07-10	1998-02-25	ラボラトワール、グラクソ、ソシエテ、アノニム	アニリド誘導体
RU2036198C1 (ru) *	1993-04-01	1995-05-27	Товарищество с ограниченной ответственностью "Полисан"	N-МЕТИЛ-N-( α,D -ГЛЮКОПИРАНОЗИЛ) АММОНИЯ-2-(АКРИДОН-9-ОН-10-ИЛ)АЦЕТАТ(ЦИКЛОФЕРОН), ОБЛАДАЮЩИЙ ИНТЕРФЕРОНОГЕННОЙ, ПРОТИВОВИРУСНОЙ, В ТОМ ЧИСЛЕ АНТИВИЧ, АНТИПАРАЗИТАРНОЙ, АНТИПРОМОТОРНОЙ И РАДИОПРОТЕКТИВНОЙ АКТИВНОСТЬЮ
US5387685A (en) *	1993-07-16	1995-02-07	American Cyanamid Co	MDR reversal agents
DE4422517A1 (de) *	1994-06-28	1996-01-04	Dresden Arzneimittel	Neue (2-(3,4-Dimethoxy-phenyl)-ethyl)-(2-phenoxy-ethyl)-amine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
JP3904599B2 (ja) *	1994-08-04	2007-04-11	シー・アンド・シー・リサーチ・ラブズ	新規なアミン誘導体、その製造方法及び抗不整脈剤としての用途
CA2201628A1 (en) *	1994-10-05	1996-04-18	Wei-Qin Tong	Parenteral pharmaceutical compositions containing gf120918a
FR2726267B1 (fr) *	1994-10-26	1998-01-02	Smithkline Beecham Lab	Nouveaux agents anti-arythmiques, compositions pharmaceutiques les contenant, et procede pour les preparer
US6245805B1 (en)	1995-10-26	2001-06-12	Baker Norton Pharmaceuticals, Inc.	Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents
US6395770B1 (en)	1995-10-26	2002-05-28	Baker Norton Pharmaceuticals, Inc.	Method and compositions for administering taxanes orally to human patients
AU1597197A (en) *	1996-02-01	1997-08-22	Byk Gulden Lomberg Chemische Fabrik Gmbh	Thienoquinolines
US6713517B1 (en)	1996-03-08	2004-03-30	Oxigene, Inc.	Use of aryl N-substituted carboxamides directly and as radio-and chemosensitizers for killing tumor and cancer cells and novel compounds for such use
RU2118532C1 (ru) *	1996-04-10	1998-09-10	Олег Викторович Травкин	Противоинфекционное, противовоспалительное и противоопухолевое лекарственное средство
GB9708805D0 (en)	1997-05-01	1997-06-25	Smithkline Beecham Plc	Compounds
GB9710612D0 (en) *	1997-05-23	1997-07-16	Glaxo Group Ltd	Synthesis of acridine derivatives
CZ9904244A3 (cs) *	1997-05-27	2001-10-17	Baker Norton Pharmaceuticals, Inc.	Pouľití taxanů, jejich derivátů, analogů nebo předléků pro přípravu farmaceutického prostředku pro perorální podávání
GB9718903D0 (en) *	1997-09-05	1997-11-12	Glaxo Group Ltd	Method,compositions and kits for increasing the oral bioavailability of pharmaceutical agents
GB9810876D0 (en)	1998-05-20	1998-07-22	Smithkline Beecham Plc	Compounds
GB9812189D0 (en) *	1998-06-05	1998-08-05	Glaxo Group Ltd	Methods and compositions for increasing penetration of HIV protease inhibitors
AU4698299A (en) *	1998-06-30	2000-01-17	Du Pont Pharmaceuticals Company	5-HT7 receptor antagonists
NZ511018A (en)	1998-10-08	2003-09-26	Smithkline Beecham Plc	Tetrahydrobenzazepine derivatives useful as modulators of dopamine D3 receptors (antipsychotic agents)
AU4955200A (en) *	1999-05-17	2000-12-05	Cancer Research Ventures Limited	A method of improving bioavailability of orally administered drugs, a method of screening for enhancers of such bioavailability and novel pharmaceutical compositions for oral delivery of drugs
EP2289549A3 (en)	1999-10-01	2011-06-15	Immunogen, Inc.	Immunoconjugates for treating cancer
US6521635B1 (en)	2000-01-20	2003-02-18	The United States Of America As Represented By The Department Of Health And Human Services	Inhibition of MXR transport by acridine derivatives
DK1261325T3 (da) *	2000-02-18	2010-12-20	New York Medical College	Tumorinhiberende sammensætninger, der indeholder nitroacridiner
KR20070087103A (ko) *	2000-03-14	2007-08-27	액테리온 파마슈티칼 리미티드	1,2,3,4-테트라하이드로이소퀴놀린 유도체
WO2001085693A1 (fr)	2000-05-11	2001-11-15	Banyu Pharmaceutical Co., Ltd.	Dérivés n-acyltétrahydroisoquinoline
CZ20031262A3 (en) *	2000-10-16	2004-03-17	Neopharm, Inc.	Liposomal formulation of mitoxantrone
JP4464814B2 (ja) *	2002-05-14	2010-05-19	アバーント・ファーマシューティカルズ・（インディア）・リミテッド	アントラニル酸誘導体の水和物の製造方法
WO2004039795A2 (en) *	2002-10-29	2004-05-13	Fujisawa Pharmaceutical Co., Ltd.	Amide compounds for the treatment of hyperlipidemia
PL1751111T3 (pl)	2004-03-01	2015-06-30	Actelion Pharmaceuticals Ltd	Podstawione pochodne 1,2,3,4-tetrahydroizochinoliny
RU2346692C2 (ru) *	2007-03-29	2009-02-20	Ефаг АО	Применение 9-оксоакридин-10-уксусной кислоты, ее солей и сложных эфиров в комбинированной терапии рака яичников, способ лечения и наборы
SE531698C2 (sv) *	2007-07-12	2009-07-07	Respiratorius Ab	Nya bronkdilaterande a,b-omättade amider
WO2015142670A1 (en) *	2014-03-15	2015-09-24	Medisyn Technologies, Inc.	Anti-diabetic compounds, pharmaceutical compositions containing them, and method to treat diabetes
WO2015018380A2 (en)	2014-07-03	2015-02-12	Cspc Zhongqi Pharmaceutical Technology(Shijiazhuang)Co., Ltd.	Therapeutic nanoparticles and the preparation methods thereof
IL277335B2 (en) *	2018-03-21	2024-03-01	Izumi Tech Llc	Analogues of alcridar with deuterium
CN115385847B (zh) *	2021-06-15	2023-09-29	山东第一医科大学(山东省医学科学院)	多取代二芳基类化合物及其制备方法和应用
CN117414367A (zh) *	2022-08-09	2024-01-19	北京清华长庚医院	一种逆转仑伐替尼耐药的药物组合物及其用途

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4250182A (en) *	1972-02-24	1981-02-10	Burroughs Wellcome Co.	Pharmaceutical composition containing acridone compounds and method of using same
US4021551A (en) *	1972-06-07	1977-05-03	Boehringer Ingelheim Gmbh	3,6-Bis-(heterocyclic aminoacyl-amino)-acridines and salts thereof
US4127573A (en) *	1972-09-06	1978-11-28	Burroughs Wellcome Co.	Ditetrazole substituted acridone compounds
DE3170001D1 (en) *	1980-09-30	1985-05-23	Bayer Ag	Method for the production of an antithrombin-heparin complex and pharmaceutical compositions containing the complex
NZ198115A (en) *	1981-08-21	1985-05-31	New Zealand Dev Finance	9-anilinoacridines;pharmaceutical compositions
NZ201084A (en) *	1982-06-25	1985-10-11	New Zealand Dev Finance	4-carboxamidoacridine derivatives and pharmaceutical compositions containing such
IN164921B (sk) *	1986-07-22	1989-07-08	Hoechst India
US5104858A (en) *	1988-09-29	1992-04-14	Yale University	Sensitizing multidrug resistant cells to antitumor agents
CA1340821C (en) *	1988-10-06	1999-11-16	Nobuyuki Fukazawa	Heterocyclic compounds and anticancer-drug reinforcing agents containing them as effective components
EP0409406B1 (en) *	1989-06-19	1993-09-08	The Wellcome Foundation Limited	Aryl-substituted amine derivatives useful in cancer therapy
AU652996B2 (en) *	1991-01-11	1994-09-15	Laboratoires Glaxo S.A.	Acridine derivatives
US5296602A (en) *	1991-03-18	1994-03-22	Sloan-Kettering Institute For Cancer Research	Multisubstituted 1-hydroxy-9-acridones with anticancer activity
US5240936A (en) *	1992-05-14	1993-08-31	Texas A&M University System	Treating or preventing ocular inflammation or systemic imflammatory disease

1992
- 1992-01-07 AU AU11543/92A patent/AU652996B2/en not_active Expired
- 1992-01-07 KR KR1019930702079A patent/KR100220538B1/ko not_active IP Right Cessation
- 1992-01-07 EP EP92100123A patent/EP0494623A1/en active Pending
- 1992-01-07 ES ES92901861T patent/ES2104887T3/es not_active Expired - Lifetime
- 1992-01-07 CZ CS931378A patent/CZ283038B6/cs not_active IP Right Cessation
- 1992-01-07 AT AT92901861T patent/ATE153660T1/de not_active IP Right Cessation
- 1992-01-07 EP EP92901861A patent/EP0569380B1/en not_active Expired - Lifetime
- 1992-01-07 HU HU9301989A patent/HUT68856A/hu unknown
- 1992-01-07 WO PCT/EP1992/000020 patent/WO1992012132A1/en active IP Right Grant
- 1992-01-07 RU RU93051543A patent/RU2119482C1/ru active
- 1992-01-07 DK DK92901861.2T patent/DK0569380T3/da active
- 1992-01-07 SG SG1996006197A patent/SG45403A1/en unknown
- 1992-01-07 CA CA002100258A patent/CA2100258C/en not_active Expired - Lifetime
- 1992-01-07 PL PL92299989A patent/PL168202B1/pl unknown
- 1992-01-07 SK SK730-93A patent/SK280864B6/sk not_active IP Right Cessation
- 1992-01-07 JP JP4501671A patent/JP2783680B2/ja not_active Expired - Lifetime
- 1992-01-07 GE GEAP19922653A patent/GEP20002210B/en unknown
- 1992-01-07 DE DE69220037T patent/DE69220037T2/de not_active Expired - Lifetime
- 1992-01-10 IL IL10063192A patent/IL100631A/en not_active IP Right Cessation
- 1992-01-10 IE IE008392A patent/IE920083A1/en not_active IP Right Cessation
- 1992-01-10 MX MX9200109A patent/MX9200109A/es unknown
- 1992-01-10 NZ NZ241278A patent/NZ241278A/en not_active IP Right Cessation
1993
- 1993-07-09 NO NO932512A patent/NO300267B1/no not_active IP Right Cessation
- 1993-07-09 FI FI933149A patent/FI103888B/fi active
1995
- 1995-06-06 US US08/468,620 patent/US5604237A/en not_active Expired - Lifetime
- 1995-06-29 HU HU95P/P00524P patent/HU211623A9/hu unknown
1997
- 1997-08-22 GR GR970402168T patent/GR3024525T3/el unknown

Also Published As

Publication number	Publication date
EP0569380B1 (en)	1997-05-28
FI103888B1 (fi)	1999-10-15
DK0569380T3 (da)	1997-12-22
CA2100258A1 (en)	1992-07-12
WO1992012132A1 (en)	1992-07-23
IE920083A1 (en)	1992-07-15
IL100631A0 (en)	1992-09-06
JP2783680B2 (ja)	1998-08-06
CZ137893A3 (en)	1994-02-16
US5604237A (en)	1997-02-18
PL168202B1 (pl)	1996-01-31
SK280864B6 (en)	2000-08-14
DE69220037T2 (de)	1997-11-06
GR3024525T3 (en)	1997-11-28
MX9200109A (es)	1992-09-01
EP0569380A1 (en)	1993-11-18
RU2119482C1 (ru)	1998-09-27
ATE153660T1 (de)	1997-06-15
ES2104887T3 (es)	1997-10-16
FI933149A0 (fi)	1993-07-09
SK73093A3 (en)	1994-01-12
GEP20002210B (en)	2000-08-25
AU1154392A (en)	1992-08-17
FI933149A (fi)	1993-07-09
FI103888B (fi)	1999-10-15
NO932512L (no)	1993-09-09
NO932512D0 (no)	1993-07-09
SG45403A1 (en)	1998-01-16
IL100631A (en)	1996-09-12
EP0494623A1 (en)	1992-07-15
KR100220538B1 (ko)	1999-09-15
CA2100258C (en)	1999-12-14
AU652996B2 (en)	1994-09-15
HU9301989D0 (en)	1993-10-28
DE69220037D1 (de)	1997-07-03
NZ241278A (en)	1994-05-26
HUT68856A (en)	1995-08-28
HU211623A9 (en)	1995-12-28
JPH06506440A (ja)	1994-07-21
CZ283038B6 (cs)	1997-12-17

Legal Events

Date	Code	Title	Description
2012-02-20	MK1K	Patent expired

Publication	Publication Date	Title
NO300267B1 (no)	1997-05-05	Akridin-derivater, samt anvendelse av slike i farmasöytiske preparater
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US5175173A (en)	1992-12-29	Carboxamides useful as antiemetic or antipsychotic agents
JP3341019B2 (ja)	2002-11-05	選択的ロイコトリエンｂ▲４▼拮抗剤活性を示す置換された単環式アリール化合物
WO1988003137A1 (en)	1988-05-05	Tetrahydroisoquinolin-2-yl derivatives of carboxylic acids as thromboxane a2 antagonists
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US5935955A (en)	1999-08-10	Pharmaceutical piperazine compounds
US4515944A (en)	1985-05-07	1,5-Diphenyl-2-haloalkylpyrazolin-3-one intermediates
WO2008090434A1 (en)	2008-07-31	Substituted n-bicyclicalkyl bicyclic carboxyamide compounds
KR20070046879A (ko)	2007-05-03	5-ｈｔ7 수용체 안타고니스트
EP0043736B1 (en)	1984-04-25	Propanolamine derivatives, their salts, processes for preparation and pharmaceutical compositions
JPH08337523A (ja)	1996-12-24	血管新生阻害剤
KR20070046878A (ko)	2007-05-03	5-ｈｔ7 수용체 안타고니스트
WO1996020179A1 (en)	1996-07-04	Piperazine-2,5-dione derivatives as modulators of multi-drug resistance
CA1260933A (en)	1989-09-26	Bicyclic lactams, processes for their preparation and their use, and formulations containing these compounds
Gan et al.	2015	Discovery, stereospecific characterization and peripheral modification of 1-(pyrrolidin-1-ylmethyl)-2-[(6-chloro-3-oxo-indan)-formyl]-1, 2, 3, 4-tetrahydroisoquinolines as novel selective κ opioid receptor agonists
Kumar	2019	Design, Synthesis and Evaluation of Novel Multifunctional Ligands for Treatment of Alzheimer's Disease
US4018758A (en)	1977-04-19	3-Aminomethylene-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid esters and intermediates leading thereto
JPH068294B2 (ja)	1994-02-02	新規な１，４−ジヒドロピリジン誘導体およびその塩
JPH05239030A (ja)	1993-09-17	アミノメチルテトラヒドロイソキノリン誘導体及びその製造方法
JPS62103080A (ja)	1987-05-13	テトラヒドロキノリン誘導体
NO861370L (no)	1987-10-09	Fremgangsm te for fremstilling av terapeutisk aktivranilin-derivater.