Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

被引：34

作者：

Ruiz-Caro, J

Basavapathruni, A

Kim, JT

Bailey, CM

Wang, LG

Anderson, KS

Hamilton, AD

Jorgensen, WL

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 03期

关键词：

NNRTI; computer-aided drug design; diarylamine; anti-HIV drug; thiazoylamine; pyrimidinylamine;

D O I：

10.1016/j.bmcl.2005.10.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Following computational analyses, potential non-nucleoside inhibitors of HIV-1 reverse transcriptase have been pursued through synthesis and assaying for anti-viral activity. The general class Het-NH-Ph-U has been considered, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Results for compounds with Het = 2-thiazoyl and 2-pyrimidinyl are the focus of this report. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：668 / 671

页数：4

共 15 条

[1] Selective deprotection of either alkyl or aryl silyl ethers from aryl, alkyl bis-silyl ethers [J].

Ankala, SV ;

Fenteany, G .

TETRAHEDRON LETTERS, 2002, 43 (27) :4729-4732

[2] Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 strains at a potency similar to that for wild-type virus [J].

Balzarini, J ;

Brouwer, WG ;

Dao, DC ;

Osika, EM ;

DeClercq, E .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (06) :1454-1466

[3] Expedient parallel synthesis of 2-amino-4-heteroarylpyrimidines [J].

Bursavich, MG ;

Lombardi, S ;

Gilbert, AM .

ORGANIC LETTERS, 2005, 7 (19) :4113-4116

[4] Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants [J].

Das, K ;

Clark, AD ;

Lewi, PJ ;

Heeres, J ;

de Jonge, MR ;

Koymans, LMH ;

Vinkers, HM ;

Daeyaert, F ;

Ludovici, DW ;

Kukla, MJ ;

De Corte, B ;

Kavash, RW ;

Ho, CY ;

Ye, H ;

Lichtenstein, MA ;

Andries, K ;

Pauwels, R ;

de Béthune, MP ;

Boyer, PL ;

Clark, P ;

Hughes, SH ;

Janssen, PAJ ;

Arnold, E .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (10) :2550-2560

[5] Concentration and pH dependent aggregation of hydrophobic drug molecules and relevance to oral bioavailability [J].

Frenkel, YV ;

Clark, AD ;

Das, K ;

Wang, YH ;

Lewi, PJ ;

Janssen, PAJ ;

Arnold, E .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :1974-1983

[6] SYNTHESIS AND ANTI-HIV-1 ACTIVITY OF 4,5,6,7-TETRAHYDRO-5-METHYLIMIDAZO[4,5,1-JK][1,4]BENZODIAZEPIN-2(1H)-ONE (TIBO) DERIVATIVES .4. [J].

HO, W ;

KUKLA, MJ ;

BRESLIN, HJ ;

LUDOVICI, DW ;

GROUS, PP ;

DIAMOND, CJ ;

MIRANDA, M ;

RODGERS, JD ;

HO, CY ;

DECLERCQ, E ;

PAUWELS, R ;

ANDRIES, K ;

JANSSEN, MAC ;

JANSSEN, PAJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (05) :794-802

[7] In search of a novel anti-HIV drug:: Multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6dimethylphenyl] amino]-2-pyrimidinyl]amino]-benzonitrile (R278474, rilpivirine) [J].

Janssen, PAJ ;

Lewi, PJ ;

Arnold, E ;

Daeyaert, F ;

de Jonge, M ;

Heeres, J ;

Koymans, L ;

Vinkers, M ;

Guillemont, J ;

Pasquier, E ;

Kukla, M ;

Ludovici, D ;

Andries, K ;

de Béthune, MP ;

Pauwels, R ;

Das, K ;

Clark, AD ;

Frenkel, YV ;

Hughes, SH ;

Medaer, B ;

De Knaep, F ;

Bohets, H ;

De Clerck, F ;

Lampo, A ;

Williams, P ;

Stoffels, P .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :1901-1909

[8] The many roles of computation in drug discovery [J].

Jorgensen, WL .

SCIENCE, 2004, 303 (5665) :1813-1818

[9] Prediction of drug solubility from structure [J].

Jorgensen, WL ;

Duffy, EM .

ADVANCED DRUG DELIVERY REVIEWS, 2002, 54 (03) :355-366

[10]

JORGENSEN WL, 2005, QIKPROP V 2 3

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