Hepatitis C virus NS3-4A serine protease inhibitors:: SAR of P′2 moiety with improved potency

被引：26

作者：

Arasappan, A

Njoroge, FG

Chan, TY

Bennett, F

Bogen, SL

Chen, K

Gu, H

Hong, L

Jao, E

Liu, YT

Lovey, RG

Parekh, T

Pike, RE

Pinto, P

Santhanam, B

Venkatraman, S

Vaccaro, H

Wang, H

Yang, X

Zhu, Z

Mckittrick, B

Saksena, AK

Girijavallabhan, V

Pichardo, J

Butkiewicz, N

Ingram, R

Malcolm, B

Prongay, A

Yao, N

Marten, B

Madison, V

Kemp, S

Levy, O

Lim-Wilby, M

Tamura, S

Gangulya, AK

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

[2] Dendreon Corp, Seattle, WA 98121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 19期

关键词：

D O I：

10.1016/j.bmcl.2005.06.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have discovered that introduction of appropriate amino acid derivatives at P-2(') position improved the binding potency of P-3-capped alpha-ketoamide inhibitors of HCV NS3 serine protease. X-ray crystal structure of one of the inhibitors (43) bound to the protease revealed the importance of the P-2(') moiety. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4180 / 4184

页数：5

相关论文

共 23 条

[1] Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as Hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex [J].

Arasappan, A ;

Njoroge, FG ;

Parekh, TN ;

Yang, XZ ;

Pichardo, J ;

Butkiewicz, N ;

Prongay, A ;

Yao, NH ;

Girijavallabhan, V .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (23) :5751-5755

[2] Replication of hepatitis C virus [J].

Bartenschlager, R ;

Lohmann, V .

JOURNAL OF GENERAL VIROLOGY, 2000, 81 :1631-1648

[3] The identification of α-ketoamides as potent inhibitors of hepatitis C virus NS3-4A proteinase [J].

Bennett, JM ;

Campbell, AD ;

Campbell, AJ ;

Carr, MG ;

Dunsdon, RM ;

Greening, JR ;

Hurst, DN ;

Jennings, NS ;

Jones, PS ;

Jordan, S ;

Kay, PB ;

O'Brien, MA ;

King-Underwood, J ;

Raynham, TM ;

Wilkinson, CS ;

Wilkinson, TCI ;

Wilson, FX .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (03) :355-357

[4] EFFICIENCY IN PEPTIDE COUPLING - 1-HYDROXY-7-AZABENZOTRIAZOLE VS 3,4-DIHYDRO-3-HYDROXY-4-OXO-1,2,3-BENZOTRIAZINE [J].

CARPINO, LA ;

EL-FAHAM, A ;

ALBERICIO, F .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (11) :3561-3564

[5] The scientific challenge of hepatitis C [J].

Cohen, J .

SCIENCE, 1999, 285 (5424) :26-30

[6] Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease:: Discovery, initial SAR, and molecular modeling [J].

Colarusso, S ;

Koch, U ;

Gerlach, B ;

Steinkühler, C ;

De Francesco, R ;

Altamura, S ;

Matassa, VG ;

Narjes, F .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (03) :345-348

[7]

*CONS PAN, 1999, J HEPATOL, V30, P956

[8] HEPATITIS-C - PROGRESS AND PROBLEMS [J].

CUTHBERT, JA .

CLINICAL MICROBIOLOGY REVIEWS, 1994, 7 (04) :505-&

[9] Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase [J].

De Francesco, R ;

Tomei, L ;

Altamura, S ;

Summa, V ;

Migliaccio, G .

ANTIVIRAL RESEARCH, 2003, 58 (01) :1-16

[10] A USEFUL 12-I-5 TRIACETOXYPERIODINANE (THE DESS-MARTIN PERIODINANE) FOR THE SELECTIVE OXIDATION OF PRIMARY OR SECONDARY ALCOHOLS AND A VARIETY OF RELATED 12-I-5 SPECIES [J].

DESS, DB ;

MARTIN, JC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (19) :7277-7287