CCR2B receptor antagonists: Conversion of a weak HTS hit to a potent lead compound

被引：51

作者：

Forbes, IT

Cooper, DG

Dodds, EK

Hickey, DMB

Ife, RJ

Meeson, M

Stockley, M

Berkhout, TA

Gohil, J

Groot, PHE

Moores, K

机构：

[1] SmithKline Beecham Pharmaceut, Dept Discovery Chem, Harlow CM19 5AD, Essex, England

[2] SmithKline Beecham Pharmaceut, Dept Vasc Biol, Harlow CM19 5AD, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(00)00347-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A weak HTS hit at the CCR2B receptor has been converted into a potent antagonist by array SAR studies. Selectivity over the closely related CCR5 receptor is also achieved. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1803 / 1806

页数：4

共 10 条

[1] A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity
Baba, M
Nishimura, O
Kanzaki, N
Okamoto, M
Sawada, H
Iizawa, Y
Shiraishi, M
Aramaki, Y
Okonogi, K
Ogawa, Y
Meguro, K
Fujino, M
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) : 5698 - 5703
[2] 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
[3] 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
[4] FRETER K, 1985, ARZNEIMITTEL-FORSCH, V35, P272
[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] LAPIERRE JM, 1998, 26 NAT MED CHEM S 14
[8] LEONARD EJ, 1994, CHALL MOD MED, V3, P25
[9] Monocyte chemoattractant protein 1 a potential regulator of monocyte recruitment in inflammatory disease
Rollins, BJ
[J]. MOLECULAR MEDICINE TODAY, 1996, 2 (05): : 198 - 204
[10] 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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