Design, synthesis, and structure-activity relationship of novel CCR2 antagonists

被引：19

作者：

Kothandaraman, Shankaran ^{[1
]}

Donnely, Karla L. ^{[1
]}

Butora, Gabor ^{[1
]}

Jiao, Richard ^{[1
]}

Pasternak, Alexander ^{[1
]}

Morriello, Gregori J. ^{[1
]}

Goble, Stephen D. ^{[1
]}

Zhou, Changyou ^{[1
]}

Mills, Sander G. ^{[1
]}

MacCoss, Malcolm ^{[1
]}

Vicario, Pasquale P. ^{[2
]}

Ayala, Julia M. ^{[2
]}

DeMartino, Julie A. ^{[2
]}

Struthers, Mary ^{[2
]}

Cascieri, Margaret A. ^{[2
]}

Yang, Lihu ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Immunol, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 06期

关键词：

CCR2; Antagonist; Chemotaxis; Aminocyclopentane carboxamide; Reductive aminations; CHEMOATTRACTANT PROTEIN-1 MCP-1; SMALL-MOLECULE; RECEPTOR ANTAGONISTS; CHEMOKINE RECEPTOR-2; HIGHLY POTENT; ATHEROSCLEROSIS; DERIVATIVES; ALCOHOLS; CHEMOTAXIS; DISCOVERY;

D O I：

10.1016/j.bmcl.2008.12.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog 59 was found to posses potent antagonistic activity. (C) 2009 Published by Elsevier Ltd.

引用

页码：1830 / 1834

页数：5

共 38 条

[1] Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
AbdelMagid, AF
Carson, KG
Harris, BD
Maryanoff, CA
Shah, RD
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (11) : 3849 - 3862
[2] Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway
Ayala, JM
Goyal, S
Liverton, NJ
Claremon, DA
O'Keefe, SJ
Hanlon, WA
[J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2000, 67 (06) : 869 - 875
[3] 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
[4] 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
[5] Drug targets in inflammation and immunomodulation
Buckle, DR
Hedgecock, CJR
[J]. DRUG DISCOVERY TODAY, 1997, 2 (08) : 325 - 332
[6] BUTORA G, UNPUB
[7] 3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2
Butora, Gabor
Jiao, Richard
Parsons, William H.
Vicario, Pasquale P.
Jin, Hong
Ayala, Julia M.
Cascieri, Margaret A.
Yang, Lihu
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (13) : 3636 - 3641
[8] 4-amino-2-alkyl-butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties
Butora, Gabor
Morriello, Gregori J.
Kothandaraman, Shankaran
Guiadeen, Deodialsingh
Pasternak, Alexander
Parsons, William H.
MacCoss, Malcolm
Vicario, Pasquale P.
Cascieri, Margaret A.
Yang, Lihu
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (18) : 4715 - 4722
[9] TOTAL SYNTHESIS OF (+/-)-HIRSUTENE
COSSY, J
BELOTTI, D
PETE, JP
[J]. TETRAHEDRON, 1990, 46 (06) : 1859 - 1870
[10] 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

← 1 2 3 4 →