Structure-activity relationship investigations of a potent and selective benzodiazepine oxytocin antagonist

被引：46

作者：

Wyatt, PG

Allen, MJ

Chilcott, J

Hickin, G

Miller, ND

Woollard, PM

机构：

[1] GlaxoSmithKline, Med Res Ctr, Dept Med Chem, Stevenage SG1 2NY, Herts, England

[2] GlaxoSmithKline, Med Res Ctr, Dept Receptor Pharmacol, Stevenage SG1 2NY, Herts, England

[3] GlaxoSmithKline, Med Res Ctr, Dept Res Biometab, Stevenage SG1 2NY, Herts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 10期

关键词：

D O I：

10.1016/S0960-894X(01)00202-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have investigated the structure-activity relationships of the 1- and 3-substituents and replacements of the 5-phenyl roup of GW405212X 1, a potent selective oxytocin antagonist. The effect of these modifications on oxytocin binding antagonism and on pharmacokinetic parameters is reported. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1301 / 1305

页数：5

相关论文

共 15 条

[1]

Allen M. J., UNPUB

[2] Development of orally active oxytocin antagonists: Studies on 1-(1-{4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2-methoxybenzoyl}piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines [J].

Bell, IM ;

Erb, JM ;

Freidinger, RM ;

Gallicchio, SN ;

Guare, JP ;

Guidotti, MT ;

Halpin, RA ;

Hobbs, DW ;

Homnick, CF ;

Kuo, MS ;

Lis, EV ;

Mathre, DJ ;

Michelson, SR ;

Pawluczyk, JM ;

Pettibone, DJ ;

Reiss, DR ;

Vickers, S ;

Williams, PD ;

Woyden, CJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (12) :2146-2163

[3] DEVELOPMENT OF 1,4-BENZODIAZEPINE CHOLECYSTOKININ TYPE-B ANTAGONISTS [J].

BOCK, MG ;

DIPARDO, RM ;

EVANS, BE ;

RITTLE, KE ;

WHITTER, WL ;

GARSKY, VM ;

GILBERT, KF ;

LEIGHTON, JL ;

CARSON, KL ;

MELLIN, EC ;

VEBER, DF ;

CHANG, RSL ;

LOTTI, VJ ;

FREEDMAN, SB ;

SMITH, AJ ;

PATEL, S ;

ANDERSON, PS ;

FREIDINGER, RM .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (26) :4276-4292

[4] Treatment of preterm labor with the oxytocin and vasopressin antagonist Atosiban [J].

Bossmar, T .

JOURNAL OF PERINATAL MEDICINE, 1998, 26 (06) :458-465

[5]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[6] Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library [J].

Evans, B ;

Pipe, A ;

Clark, L ;

Banks, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (10) :1297-1300

[7] Medical progress - Prevention of premature birth [J].

Goldenberg, RL ;

Rouse, DJ .

NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (05) :313-320

[8] Oxytocin receptor antagonists - Update [J].

Goodwin, TM ;

Zograbyan, A .

CLINICS IN PERINATOLOGY, 1998, 25 (04) :859-+

[9] A risk-benefit assessment of therapies for premature labour [J].

Higby, K ;

Suiter, CR .

DRUG SAFETY, 1999, 21 (01) :35-56

[10] The molecular mechanisms of term and preterm labor: Recent progress and clinical implications [J].

Keelan, JA ;

Coleman, M ;

Mitchell, MD .

CLINICAL OBSTETRICS AND GYNECOLOGY, 1997, 40 (03) :460-478