Probing Multidrug-Resistance and Protein-Ligand Interactions with Oxatricyclic Designed Ligands in HIV-1 Protease Inhibitors

被引：45

作者：

Ghosh, Arun K. ^{[1
]}

Xu, Chun-Xiao ^{[1
]}

Rao, Kalapala Venkateswara ^{[1
]}

Baldridge, Abigail ^{[1
]}

Agniswamy, Johnson ^{[2
]}

Wang, Yuan-Fang ^{[2
]}

Weber, Irene T. ^{[2
]}

Aoki, Manabu ^{[3
,4
]}

Miguel, Salcedo Gomez Pedro ^{[3
,4
]}

Amano, Masayuki ^{[3
,4
]}

Mitsuya, Hiroaki ^{[3
,4
,5
]}

机构：

[1] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA

[2] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA

[3] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan

[4] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan

[5] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA

来源：

CHEMMEDCHEM | 2010年 / 5卷 / 11期

基金：

美国国家卫生研究院;

关键词：

dimerization inhibitors; HIV-1; protease; multidrug resistance; oxatricyclic ligands; X-ray crystallography; RESOLUTION CRYSTAL-STRUCTURES; HIGH-AFFINITY P-2-LIGANDS; HUMAN-IMMUNODEFICIENCY; BIOLOGICAL EVALUATION; POTENT; BACKBONE; ALCOHOLS; PI;

D O I：

10.1002/cmdc.201000318

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A healthier HAART: We report the design, synthesis, biological evaluation, and X-ray crystallographic analysis of a new class of HIV-1 protease inhibitors. Compound 4 proved to be an extremely potent inhibitor toward various multidrug-resistant HIV-1 variants, representing a near 10-fold improvement over darunavir (DRV). Compound 4 also blocked protease dimerization with at least 10-fold greater potency than DRV. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：1850 / 1854

页数：5

共 32 条

[1] Conversion of D-glucals into L-glycals and mirror-image carbohydrates [J].

Boulineau, FP ;

Wei, A .

ORGANIC LETTERS, 2004, 6 (01) :119-121

[2] TOTAL SYNTHESIS OF GINKGOLIDE-A [J].

COREY, EJ ;

GHOSH, AK .

TETRAHEDRON LETTERS, 1988, 29 (26) :3205-3206

[3] ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETIC ACID, A VERSATILE REAGENT FOR DETERMINATION OF ENANTIOMERIC COMPOSITION OF ALCOHOLS AND AMINES [J].

DALE, JA ;

DULL, DL ;

MOSHER, HS .

JOURNAL OF ORGANIC CHEMISTRY, 1969, 34 (09) :2543-&

[4]

de Mendoza C, 2004, CURR DRUG METAB, V5, P321

[5] 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

[6] HIV-protease inhibitors [J].

Flexner, C .

NEW ENGLAND JOURNAL OF MEDICINE, 1998, 338 (18) :1281-1292

[7] Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere [J].

Ghosh, AK ;

Kincaid, JF ;

Cho, WH ;

Walters, DE ;

Krishnan, K ;

Hussain, KA ;

Koo, Y ;

Cho, H ;

Rudall, C ;

Holland, L ;

Buthod, J .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (06) :687-690

[8] Structure-based design of non-peptide HIV protease inhibitors [J].

Ghosh, AK ;

Shin, D ;

Swanson, L ;

Krishnan, K ;

Cho, H ;

Hussain, KA ;

Walters, DE ;

Holland, L ;

Buthod, J .

FARMACO, 2001, 56 (1-2) :29-32

[9] Nonpeptidal P-2 ligands for HIV protease inhibitors: Structure-based design, synthesis, and biological evaluation [J].

Ghosh, AK ;

Kincaid, JF ;

Walters, DE ;

Chen, Y ;

Chaudhuri, NC ;

Thompson, WJ ;

Culberson, C ;

Fitzgerald, PMD ;

Lee, HY ;

McKee, SP ;

Munson, PM ;

Duong, TT ;

Darke, PL ;

Zugay, JA ;

Schleif, WA ;

Axel, MG ;

Lin, J ;

Huff, JR .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (17) :3278-3290

[10] SYNTHESIS AND OPTICAL RESOLUTION OF HIGH-AFFINITY P-2-LIGANDS FOR HIV-1 PROTEASE INHIBITORS [J].

GHOSH, AK ;

CHEN, Y .

TETRAHEDRON LETTERS, 1995, 36 (04) :505-508

← 1 2 3 4 →