1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 4: Synthesis of N-1 acidic functionality affording analogues with enhanced antiviral activity against HIV

被引：39

作者：

Lynch, CL

Hale, JJ

Budhu, RJ

Gentry, AL

Mills, SG

Chapman, KT

MacCoss, M

Malkowitz, L

Springer, MS

Gould, SL

DeMartino, JA

Siciliano, SJ

Cascieri, MA

Carella, A

Carver, G

Holmes, K

Schleif, WA

Danzeisen, R

Hazuda, D

Kessler, J

Lineberger, J

Miller, M

Emini, EA

机构：

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

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(02)00606-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of alpha-(pyrrolidin-1-yl)acetic acids is presented as selective and potent antivirals against HIV. Several of the pyrrolidine zwitterions demonstrated reasonable in vitro properties, enhanced antiviral activities and improved pharmacokinetic profiles over pyrrolidine 1. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：3001 / 3004

页数：4

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共 17 条

[1] Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures [J].

AbdelMagid, AF ;

Carson, KG ;

Harris, BD ;

Maryanoff, CA ;

Shah, RD .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (11) :3849-3862

[2] A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity [J].

Baba, M ;

Nishimura, O ;

Kanzaki, N ;

Okamoto, M ;

Sawada, H ;

Iizawa, Y ;

Shiraishi, M ;

Aramaki, Y ;

Okonogi, K ;

Ogawa, Y ;

Meguro, K ;

Fujino, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) :5698-5703

[3] SELECTIVE REDUCTIONS .37. ASYMMETRIC REDUCTION OF PROCHIRAL KETONES WITH B-(3-PINANYL)-9-BORABICYCLO[3.3.1]NONANE [J].

BROWN, HC ;

PAI, GG .

JOURNAL OF ORGANIC CHEMISTRY, 1985, 50 (09) :1384-1394

[4] ASYMMETRIC OXIDATION OF ESTER AND AMIDE ENOLATES USING NEW (CAMPHORYLSULFONYL)OXAZIRIDINES [J].

DAVIS, FA ;

HAQUE, MS ;

ULATOWSKI, TG ;

TOWSON, JC .

JOURNAL OF ORGANIC CHEMISTRY, 1986, 51 (12) :2402-2404

[5] AN EFFICIENT SYNTHESIS OF N-HYDROXY-ALPHA-AMINO ACID-DERIVATIVES OF HIGH OPTICAL PURITY [J].

FEENSTRA, RW ;

STOKKINGREEF, EHM ;

NIVARD, RJF ;

OTTENHEIJM, HCJ .

TETRAHEDRON LETTERS, 1987, 28 (11) :1215-1218

[6] 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 [J].

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 .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (18) :2475-2479

[7] 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: Polar functionality and its effect on anti-HIV-1 activity [J].

Hale, JJ ;

Budhu, RJ ;

Mills, SG ;

MacCoss, M ;

Gould, SL ;

DeMartino, JA ;

Springer, MS ;

Siciliano, SJ ;

Malkowitz, L ;

Schleif, WA ;

Hazuda, D ;

Miller, M ;

Kessler, J ;

Danzeisen, R ;

Holmes, K ;

Lineberger, J ;

Carella, A ;

Carver, G ;

Emini, EA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (20) :2997-3000

[8] 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: Lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity [J].

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 .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (20) :2741-2745

[9] 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: Discovery of the pyrrolidine scaffold and determination of its stereochemical requirements [J].

Hale, JJ ;

Budhu, RJ ;

Mills, SG ;

MacCoss, M ;

Malkowitz, L ;

Siciliano, S ;

Gould, SL ;

DeMartino, JA ;

Springer, MS .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (11) :1437-1440

[10] Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells [J].

Hazuda, DJ ;

Felock, P ;

Witmer, M ;

Wolfe, A ;

Stillmock, K ;

Grobler, JA ;

Espeseth, A ;

Gabryelski, L ;

Schleif, W ;

Blau, C ;

Miller, MD .

SCIENCE, 2000, 287 (5453) :646-650