学术探索
学术期刊
新闻热点
数据分析
智能评审

2,5-diketopiperazines as potent and selective oxytocin antagonists - 1: identification, stereochemistry and initial SAR

被引：59
作者：
Wyatt, PG
Allen, MJ
Borthwick, AD
Davies, DE
Exall, AM
Hatley, RJD
Irving, WR
Livermore, DG
Miller, ND
Nerozzi, F
Sollis, SL
Szardenings, AK
机构：
[1] GlaxoSmithKline Res & Dev Ltd, Dept Med Chem, CVU UK, Med Res Ctr, Stevenage SG1 2NY, Herts, England
[2] GlaxoSmithKline Res & Dev Ltd, ADCP Harlow Res 2, Harlow CM19 5AW, Essex, England
[3] Affymax Res Inst, Santa Clara, CA 95051 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 10期
关键词：
oxytocin; oxytocin receptor; preterm birth; antagonists; unencoded libraries; 2,5-diketopiperidines; Ugi reaction; screening; pooled libraries; solid phase; structure-activity relationships;
D O I：
10.1016/j.bmcl.2005.03.045
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2579 / 2582
页数：4
相关论文
共 9 条
[1]   The solution phase synthesis of diketopiperazine libraries via the Ugi reaction: Novel application of Armstrong's convertible isonitrile. [J].
Hulme, C ;
Morrissette, MM ;
Volz, FA ;
Burns, CJ .
TETRAHEDRON LETTERS, 1998, 39 (10) :1113-1116
[2]   Oxytocin and its receptor in the process of parturition [J].
Mitchell, BF ;
Schmid, B .
JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION, 2001, 8 (03) :122-133
[3]   Preterm labour: An overview of current and emerging therapeutics [J].
Schwarz, MK ;
Page, P .
CURRENT MEDICINAL CHEMISTRY, 2003, 10 (15) :1441-1468
[4]  
SOLLIS SL, 2005, IN PRESS J ORG CHEM, V70
[5]   A simple procedure for the solid phase synthesis of diketopiperazine and diketomorpholine derivatives [J].
Szardenings, AK ;
Burkoth, TS ;
Lu, HH ;
Tien, DW ;
Campbell, DA .
TETRAHEDRON, 1997, 53 (19) :6573-6593
[6]  
Vatish M, 2002, EXPERT OPIN THER PAT, V12, P1403
[7]   Identification of potent and selective oxytocin antagonists. Part 2: Further investigation of benzofuran derivatives [J].
Wyatt, PG ;
Allen, MJ ;
Chilcott, J ;
Gardner, CJ ;
Livermore, DG ;
Mordaunt, JE ;
Nerozzi, F ;
Patel, M ;
Perren, MJ ;
Weingarten, GG ;
Shabbir, S ;
Woollard, PM ;
Zhou, P .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (10) :1405-1411
[8]   Identification of potent and selective oxytocin antagonists. Part 1: Indole and benzofuran derivatives [J].
Wyatt, PG ;
Allen, MJ ;
Chilcott, J ;
Foster, A ;
Livermore, DG ;
Mordaunt, JE ;
Scicinski, J ;
Woollard, PM .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (10) :1399-1404
[9]   Structure-activity relationship investigations of a potent and selective benzodiazepine oxytocin antagonist [J].
Wyatt, PG ;
Allen, MJ ;
Chilcott, J ;
Hickin, G ;
Miller, ND ;
Woollard, PM .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (10) :1301-1305
1