NOVEL PSEUDOSYMMETRIC INHIBITORS OF HIV-1 PROTEASE

被引：12

作者：

FASSLER, A

ROSEL, J

GRUTTER, M

TINTELNOTBLOMLEY, M

ALTERI, E

BOLD, G

LANG, M

机构：

[1] Research Laboratories, Pharmaceutical Division, Ciba-Geigy Ltd.

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1993年 / 3卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(01)80775-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds containing the easily accessible Phe[CH(OH)CH2N(NH)]Phe dipeptide isostere as a non-hydrolyzable replacement of the scissile amide bond in the natural substrate are potent inhibitors of HIV-1 protease. The expected symmetric binding pattern of the most potent inhibitor in this series (CGP 53820, IC50 = 9 nM) is illustrated by the X-ray analysis performed with the corresponding enzyme-inhibitor complex.

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页码：2837 / 2842

页数：6

相关论文

共 41 条

[1] HIGHLY DIASTEREOSELECTIVE ALKYLATIONS OF CHIRAL AMIDE ENOLATES - NEW ROUTES TO HYDROXYETHYLENE DIPEPTIDE ISOSTERE INHIBITORS OF HIV-1 PROTEASE [J].

ASKIN, D ;

WALLACE, MA ;

VACCA, JP ;

REAMER, RA ;

VOLANTE, RP ;

SHINKAI, I .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (10) :2771-2773

[2] THE USE OF HIV-1 PROTEASE STRUCTURE IN INHIBITOR DESIGN [J].

BABINE, RE ;

ZHANG, N ;

JURGENS, AR ;

SCHOW, SR ;

DESAI, PR ;

JAMES, JC ;

SEMMELHACK, MF .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (06) :541-546

[3] ISOLATION OF A T-LYMPHOTROPIC RETROVIRUS FROM A PATIENT AT RISK FOR ACQUIRED IMMUNE-DEFICIENCY SYNDROME (AIDS) [J].

BARRESINOUSSI, F ;

CHERMANN, JC ;

REY, F ;

NUGEYRE, MT ;

CHAMARET, S ;

GRUEST, J ;

DAUGUET, C ;

AXLERBLIN, C ;

VEZINETBRUN, F ;

ROUZIOUX, C ;

ROZENBAUM, W ;

MONTAGNIER, L .

SCIENCE, 1983, 220 (4599) :868-871

[4] X-RAY CRYSTAL-STRUCTURE OF THE HIV PROTEASE COMPLEX WITH L-700,417, AN INHIBITOR WITH PSEUDO C2 SYMMETRY [J].

BONE, R ;

VACCA, JP ;

ANDERSON, PS ;

HOLLOWAY, MK .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (24) :9382-9384

[5] SYNTHESIS OF C2-SYMMETRICAL AND PSEUDOSYMMETRIC HIV-1 PROTEASE INHIBITORS FROM D-MANNITOL AND D-ARABITOL [J].

CHENERA, B ;

BOEHM, JC ;

DREYER, GB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1991, 1 (04) :219-222

[6] THE HIV-1 PROTEASE AS A THERAPEUTIC TARGET FOR AIDS [J].

DEBOUCK, C .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 1992, 8 (02) :153-164

[7] STEREOCONTROLLED ADDITION OF PROPIONATE HOMOENOLATE EQUIVALENTS TO CHIRAL ALPHA-AMINO ALDEHYDES [J].

DECAMP, AE ;

KAWAGUCHI, AT ;

VOLANTE, RP ;

SHINKAI, I .

TETRAHEDRON LETTERS, 1991, 32 (16) :1867-1870

[8]

DREYER G, 1991, Patent No. 9200954

[9] POLYPEPTIDES .13. PREPARATION OF ALPHA-AZA-AMINO-ACID (CARBAZIC ACID) DERIVATIVES AND INTERMEDIATES FOR PREPARATION OF ALPHA-AZA-PEPTIDES [J].

DUTTA, AS ;

MORLEY, JS .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1975, (17) :1712-1720

[10] DESIGN, ACTIVITY, AND 2.8 A CRYSTAL-STRUCTURE OF A C2 SYMMETRICAL INHIBITOR COMPLEXED TO HIV-1 PROTEASE [J].

ERICKSON, J ;

NEIDHART, DJ ;

VANDRIE, J ;

KEMPF, DJ ;

WANG, XC ;

NORBECK, DW ;

PLATTNER, JJ ;

RITTENHOUSE, JW ;

TURON, M ;

WIDEBURG, N ;

KOHLBRENNER, WE ;

SIMMER, R ;

HELFRICH, R ;

PAUL, DA ;

KNIGGE, M .

SCIENCE, 1990, 249 (4968) :527-533

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