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

页码：2177 / 2180

页数：4

共 9 条

[1] Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis
Boring, L
Gosling, J
Cleary, M
Charo, IF
[J]. 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
CHARO, IF
MYERS, SJ
HERMAN, A
FRANCI, C
CONNOLLY, AJ
COUGHLIN, SR
[J]. 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
Forbes, IT
Cooper, DG
Dodds, EK
Hickey, DMB
Ife, RJ
Meeson, M
Stockley, M
Berkhout, TA
Gohil, J
Groot, PHE
Moores, K
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (16) : 1803 - 1806
[4] Highly stereoselective synthesis of exo and endo indolotropanes
Forbes, IT
[J]. 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
Gong, JH
Ratkay, LG
Waterfield, JD
ClarkLewis, I
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (01) : 131 - 137
[6] MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B
Gosling, J
Slaymaker, S
Gu, L
Tseng, S
Zlot, CH
Young, SG
Rollins, BJ
Charo, IF
[J]. 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
Rollins, BJ
[J]. MOLECULAR MEDICINE TODAY, 1996, 2 (05): : 198 - 204
[9] Opportunities for novel therapeutic agents acting at chemokine receptors
Saunders, J
Tarby, CM
[J]. DRUG DISCOVERY TODAY, 1999, 4 (02) : 80 - 92

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