Synthesis of novel HIV-1 protease inhibitors based on carbohydrate scaffolds

被引：47

作者：

Murphy, PV ^{[1
]}

O'Brien, JL

Gorey-Feret, LJ

Smith, AB

机构：

[1] Natl Univ Ireland Univ Coll Dublin, Dept Chem, Ctr Synth & Chem Biol, Inst Biomol & Biomed Res, Dublin 4, Ireland

[2] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA

[3] Bristol Myers Squibb Co, Wilmington, DE USA

来源：

TETRAHEDRON | 2003年 / 59卷 / 13期

基金：

英国惠康基金;

关键词：

HIV-1; inhibitors; aspartic acid; carbohydrate based peptidomimetics;

D O I：

10.1016/S0040-4020(03)00208-4

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The synthesis of peptidomimetic inhibitors of HIV-1 protease based on 6-deoxy-6-aniino-beta-D-glucopyranoside and 6-deoxy-6-amino- beta-D-mannopyranoside scaffolds has been achieved. The inhibitors had IC50 values in the micromolar range. The results provide a platform for the development of more potent carbohydrate based inhibitors of HIV-1 and other aspartic proteases. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：2259 / 2271

页数：13

共 74 条

[1] Molecular recognition of protein-ligand complexes: Applications to drug design [J].

Babine, RE ;

Bender, SL .

CHEMICAL REVIEWS, 1997, 97 (05) :1359-1472

[2] Antibacterial activity of synthetic analogues based on the disaccharide structure of moenomycin, an inhibitor of bacterial transglycosylase [J].

Baizman, ER ;

Branstrom, AA ;

Longley, CB ;

Allanson, N ;

Sofia, MJ ;

Gange, D ;

Goldman, RC .

MICROBIOLOGY-SGM, 2000, 146 :3129-3140

[3] EXO-6-BENZYL-EXO-2-(META-HYDROXYPHENYL)-1-DIMETHYLAMINOMETHYLBICYCLO[2.2.2.]OCTANE - A NONPEPTIDE MIMIC OF ENKEPHALINS [J].

BELANGER, PC ;

DUFRESNE, C .

CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1986, 64 (08) :1514-1520

[4]

Boer J, 2001, ANGEW CHEM INT EDIT, V40, P3870, DOI 10.1002/1521-3773(20011015)40:20<3870::AID-ANIE3870>3.0.CO

[5]

2-X

[6] MULTIPLE HIGHLY DIVERSE STRUCTURES COMPLEMENTARY TO ENZYME BINDING-SITES - RESULTS OF EXTENSIVE APPLICATION OF A DE-NOVO DESIGN METHOD INCORPORATING COMBINATORIAL GROWTH [J].

BOHACEK, RS ;

MCMARTIN, C .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (13) :5560-5571

[7] Potential HIV protease inhibitors: Preparation of di-N-alkylated 2-, 6-, and 2,6-aminodeoxy-derivatives of D-glucose by direct displacement and by a novel reductive-alkylation procedure [J].

Cai, JQ ;

Davison, BE ;

Ganellin, CR ;

Thaisrivongs, S ;

Wibley, KS .

CARBOHYDRATE RESEARCH, 1997, 300 (02) :109-117

[8] Design and synthesis of unsymmetrical peptidyl urea inhibitors of aspartic peptidases [J].

Dales, NA ;

Bohacek, RS ;

Satyshur, KA ;

Rich, DH .

ORGANIC LETTERS, 2001, 3 (15) :2313-2316

[9]

Davis AM, 1999, ANGEW CHEM INT EDIT, V38, P737, DOI 10.1002/(SICI)1521-3773(19990315)38:6<736::AID-ANIE736>3.0.CO

[10]

2-R

← 1 2 3 4 5 6 7 8 →