Inhibition of human rhinovirus 3C protease by homophthalimides

被引：20

作者：

Jungheim, LN

Cohen, JD

Johnson, RB

Villarreal, EC

Wakulchik, M

Loncharich, RJ

Wang, QM

机构：

[1] Lilly Research Laboratories, Eli Lilly and Company, Indianapolis

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(97)00268-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Homophthalimides 2a and 3a were found to be inhibitors of Rhinovirus 3C protease through a blind screening effort. SAR studies resulted in compound 3g, which exhibited improved enzyme inhibition, in addition to whole cell antiviral activity. Molecular modeling studies suggest a preferred enzyme/inhibitor interaction, and LC/MS experiments confirmed tight/covalent binding of 3g to the enzyme. (C) 1997 Elsevier Science Ltd.

引用

收藏

页码：1589 / 1594

页数：6

相关论文

共 17 条

[1] CHARMM - A PROGRAM FOR MACROMOLECULAR ENERGY, MINIMIZATION, AND DYNAMICS CALCULATIONS [J].

BROOKS, BR ;

BRUCCOLERI, RE ;

OLAFSON, BD ;

STATES, DJ ;

SWAMINATHAN, S ;

KARPLUS, M .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1983, 4 (02) :187-217

[2]

COUCH RB, 1990, VIROLOGY, P607

[3] Simple in vitro translation assay to analyze inhibitors of rhinovirus proteases [J].

Heinz, BA ;

Tang, J ;

Labus, JM ;

Chadwell, FW ;

Kaldor, SW ;

Hammond, M .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (01) :267-270

[4] A-PRIORI PREDICTION OF ACTIVITY FOR HIV-1 PROTEASE INHIBITORS EMPLOYING ENERGY MINIMIZATION IN THE ACTIVE-SITE [J].

HOLLOWAY, MK ;

WAI, JM ;

HALGREN, TA ;

FITZGERALD, PMD ;

VACCA, JP ;

DORSEY, BD ;

LEVIN, RB ;

THOMPSON, WJ ;

CHEN, LJ ;

DESOLMS, SJ ;

GAFFIN, N ;

GHOSH, AK ;

GIULIANI, EA ;

GRAHAM, SL ;

GUARE, JP ;

HUNGATE, RW ;

LYLE, TA ;

SANDERS, WM ;

TUCKER, TJ ;

WIGGINS, M ;

WISCOUNT, CM ;

WOLTERSDORF, OW ;

YOUNG, SD ;

DARKE, PL ;

ZUGAY, JA .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (02) :305-317

[5] N-(CARBOBENZYLOXY)ISATIN - A SLOW BINDING ALPHA-KETO LACTAM INHIBITOR OF ALPHA-CHYMOTRYPSIN [J].

IYER, RA ;

HANNA, PE .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (01) :89-92

[6] GLUTAMINE-DERIVED ALDEHYDES FOR THE INHIBITION OF HUMAN RHINOVIRUS 3C PROTEASE [J].

KALDOR, SW ;

HAMMOND, M ;

DRESSMAN, BA ;

LABUS, JM ;

CHADWELL, FW ;

KLINE, AD ;

HEINZ, BA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (17) :2021-2026

[7] STRUCTURE OF HUMAN RHINOVIRUS 3C PROTEASE REVEALS A TRYPSIN-LIKE POLYPEPTIDE FOLD, RNA-BINDING SITE, AND MEANS FOR CLEAVING PRECURSOR POLYPROTEIN [J].

MATTHEWS, DA ;

SMITH, WW ;

FERRE, RA ;

CONDON, B ;

BUDAHAZI, G ;

SISSON, W ;

VILLAFRANCA, JE ;

JANSON, CA ;

MCELROY, HE ;

GRIBSKOV, CL ;

WORLAND, S .

CELL, 1994, 77 (05) :761-771

[8] PICORNAVIRAL PROCESSING - SOME NEW IDEAS [J].

PALMENBERG, AC .

JOURNAL OF CELLULAR BIOCHEMISTRY, 1987, 33 (03) :191-198

[9] PICORNAVIRUS NONSTRUCTURAL PROTEINS - EMERGING ROLES IN VIRUS-REPLICATION AND INHIBITION OF HOST-CELL FUNCTIONS [J].

PORTER, AG .

JOURNAL OF VIROLOGY, 1993, 67 (12) :6917-6921

[10] POTENT INHIBITOR OF THE HUMAN RHINOVIRUS (HRV) 3C PROTEASE CONTAINING A BACKBONE MODIFIED GLUTAMINE [J].

SHAM, HL ;

ROSENBROOK, W ;

KATI, W ;

BETEBENNER, DA ;

WIDEBURG, NE ;

SALDIVAR, A ;

PLATTNER, JJ ;

NORBECK, DW .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1995, (09) :1081-1082