Design and synthesis of ethyl pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease

被引：16

作者：

Slater, MJ ^{[1
]}

Andrews, DM ^{[1
]}

Baker, G ^{[1
]}

Bethell, SS ^{[1
]}

Carey, S ^{[1
]}

Chaignot, H ^{[1
]}

Clarke, B ^{[1
]}

Coomber, B ^{[1
]}

Ellis, M ^{[1
]}

Good, A ^{[1
]}

Gray, N ^{[1
]}

Hardy, G ^{[1
]}

Jones, P ^{[1
]}

Mills, G ^{[1
]}

Robinson, E ^{[1
]}

机构：

[1] GlaxoSmithKline Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 23期

关键词：

D O I：

10.1016/S0960-894X(02)00789-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a pyrrolidine-5,5-trans-lactam template, we have designed small. neutral. mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 11a, with an alpha-ethyl P1 substituent and a Boc-valine substituent at the pyrrolidine nitrogen, has an IC50 = 30 muM. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：3359 / 3362

页数：4

共 19 条

[1]

ALTER MJ, 1997, HEPATOLOGY S1, V26, P62

[2] Design and synthesis of pyrrolidine-5,5-trans-lactams (5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease.: 1.: The α-methyl-trans-lactam template [J].

Borthwick, AD ;

Angier, SJ ;

Crame, AJ ;

Exall, AM ;

Haley, TM ;

Hart, GJ ;

Mason, AM ;

Pennell, AMK ;

Weingarten, GG .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (23) :4452-4464

[3]

BROWN JL, 1998, LANCET, V351, P83

[4] Molecular virology of hepatitis C virus [J].

Clarke, B .

JOURNAL OF GENERAL VIROLOGY, 1997, 78 :2397-2410

[5] Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C [J].

Davis, GL ;

Esteban-Mur, R ;

Rustgi, V ;

Hoefs, J ;

Gordon, SC ;

Trepo, C ;

Shiffman, ML ;

Zeuzem, S ;

Craxi, A ;

Ling, MH ;

Albrecht, J .

NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (21) :1493-1499

[6] Hepatitis C [J].

Di Bisceglie, AM .

LANCET, 1998, 351 (9099) :351-355

[7]

GERBER MA, 1993, J HEPATOL S3, V17, P108

[8] Therapy of viral hepatitis [J].

Hoofnagle, JH .

DIGESTION, 1998, 59 (05) :563-578

[9] Hepatitis C: The clinical spectrum of disease [J].

Hoofnagle, JH .

HEPATOLOGY, 1997, 26 (03) :S15-S20

[10]

KIM JL, 1996, CELL, V8, P344

← 1 2 →