Conformationally restricted indolopiperidine derivatives as potent CCR2B receptor antagonists

被引：39
作者：
Witherington, J
Bordas, V
Cooper, DG
Forbes, IT
Gribble, AD
Ife, RJ
Berkhout, T
Gohil, J
Groot, PHE
机构：
[1] GlaxoSmithKline Pharmaceut, Dept Discovery Chem, Harlow CM19 5AD, Essex, England
[2] GlaxoSmithKline Pharmaceut, Dept Vasc Biol, Harlow CM19 5AD, Essex, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 16期
关键词：
D O I：
10.1016/S0960-894X(01)00397-3
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The preparation and biological evaluation of a series of indolopiperidine CCR2B receptor antagonists possessing a conformationally restricted C-5 linker chain in combination with a restricted piperidine ring are described. Compared to the parent compound 1, analogue 8 shows a dramatic improvement in selectivity against a range of 5-HT and dopaminergic receptors. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：2177 / 2180
页数：4
相关论文
共 9 条
[1]   Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis [J].
Boring, L ;
Gosling, J ;
Cleary, M ;
Charo, IF .
NATURE, 1998, 394 (6696) :894-897
[2]   MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF 2 MONOCYTE CHEMOATTRACTANT PROTEIN-1 RECEPTORS REVEALS ALTERNATIVE SPLICING OF THE CARBOXYL-TERMINAL TAILS [J].
CHARO, IF ;
MYERS, SJ ;
HERMAN, A ;
FRANCI, C ;
CONNOLLY, AJ ;
COUGHLIN, SR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (07) :2752-2756
[3]   CCR2B receptor antagonists: Conversion of a weak HTS hit to a potent lead compound [J].
Forbes, IT ;
Cooper, DG ;
Dodds, EK ;
Hickey, DMB ;
Ife, RJ ;
Meeson, M ;
Stockley, M ;
Berkhout, TA ;
Gohil, J ;
Groot, PHE ;
Moores, K .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (16) :1803-1806
[4]   Highly stereoselective synthesis of exo and endo indolotropanes [J].
Forbes, IT .
TETRAHEDRON LETTERS, 1999, 40 (52) :9293-9295
[5]   An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model [J].
Gong, JH ;
Ratkay, LG ;
Waterfield, JD ;
ClarkLewis, I .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (01) :131-137
[6]   MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B [J].
Gosling, J ;
Slaymaker, S ;
Gu, L ;
Tseng, S ;
Zlot, CH ;
Young, SG ;
Rollins, BJ ;
Charo, IF .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (06) :773-778
[7]  
LEONARD EJ, 1994, CHALL MOD MED, V3, P25
[8]   Monocyte chemoattractant protein 1 a potential regulator of monocyte recruitment in inflammatory disease [J].
Rollins, BJ .
MOLECULAR MEDICINE TODAY, 1996, 2 (05) :198-204
[9]   Opportunities for novel therapeutic agents acting at chemokine receptors [J].
Saunders, J ;
Tarby, CM .
DRUG DISCOVERY TODAY, 1999, 4 (02) :80-92
1