Synthesis and evaluation of CCR5 antagonists containing modified 4-piperidinyl-2-phenyl-1-(phenylsulfonylamino)-butane

被引：23

作者：

Shah, SK

Chen, N

Guthikonda, RN

Mills, SG

Malkowitz, L

Springer, MS

Gould, SL

DeMartino, JA

Carella, A

Carver, G

Holmes, K

Schleif, WA

Danzeisen, R

Hazuda, D

Kessler, J

Lineberger, J

Miller, M

Emini, EA

MacCoss, M

机构：

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

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

[3] Merck Res Labs, Dept Antiviral Res, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 04期

关键词：

CCR5; antagonist; anti-HIV; piperidine;

D O I：

10.1016/j.bmcl.2004.12.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis of analogs containing more rigid bicyclic piperidine replacements for the 4-benzyloxycarbonyl-(ethyl)aminopiperidine moiety of the CCR5 antagonist structure, 1, is described. Although similar binding affinity to the lead was achieved with some analogs they were overall less potent anti-HIV agents suggesting that other features besides CCR5 binding are required for good anti-viral activity. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：977 / 982

页数：6

共 16 条

[1] BAROUDY BM, 2002, AIDS 14 INT C NEW 1
[2] CALDWELL CG, 2000, 220 ACS NAT M WASH D
[3] DOWD W, 1981, Patent No. 4237304
[4] Host factors and the pathogenesis of HIV-induced disease
Fauci, AS
[J]. NATURE, 1996, 384 (6609) : 529 - 534
[5] Antagonists of the human CCR5 receptor as anti-HIV-1 agents.: Part 4:: Synthesis and structure-activity relationships for 1-[N(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N- (benzyloxycarbonyl)amino)piperidin-1-yl)butanes
Finke, PE
Oates, B
Mills, SG
MacCoss, M
Malkowitz, L
Springer, MS
Gould, SL
DeMartino, JA
Carella, A
Carver, G
Holmes, K
Danzeisen, R
Hazuda, D
Kessler, J
Lineberger, J
Miller, M
Schleif, WA
Emini, EA
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (18) : 2475 - 2479
[6] Antagonists of the human CCR5 receptor as anti-HIV-1 agents.: Part 2:: Structure-activity relationships for substituted 2-aryl-1-[N-(methyl)-N-(phenylsulfonyl) amino]-4-(piperidin-1-yl)butanes
Finke, PE
Meurer, LC
Oates, B
Mills, SG
MacCoss, M
Malkowitz, L
Springer, MS
Daugherty, BL
Gould, SL
DeMartino, JA
Siciliano, SJ
Carella, A
Carver, G
Holmes, K
Danzeisen, R
Hazuda, D
Kessler, J
Lineberger, J
Miller, M
Schleif, WA
Emini, EA
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (02) : 265 - 270
[7] 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: Lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity
Hale, JJ
Budhu, RJ
Holson, EB
Finke, PE
Oates, B
Mills, SG
MacCoss, M
Gould, SL
DeMartino, JA
Springer, MS
Siciliano, S
Malkowitz, L
Schleif, WA
Hazuda, D
Miller, M
Kessler, J
Danzeisen, R
Holmes, K
Lineberger, J
Carella, A
Carver, G
Emini, E
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (20) : 2741 - 2745
[8] 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: Discovery of the pyrrolidine scaffold and determination of its stereochemical requirements
Hale, JJ
Budhu, RJ
Mills, SG
MacCoss, M
Malkowitz, L
Siciliano, S
Gould, SL
DeMartino, JA
Springer, MS
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (11) : 1437 - 1440
[9] Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells
Hazuda, DJ
Felock, P
Witmer, M
Wolfe, A
Stillmock, K
Grobler, JA
Espeseth, A
Gabryelski, L
Schleif, W
Blau, C
Miller, MD
[J]. SCIENCE, 2000, 287 (5453) : 646 - 650
[10] Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors
Kazmierski, W
Bifulco, N
Yang, HB
Boone, L
DeAnda, F
Watson, C
Kenakin, T
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (13) : 2663 - 2676

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