Synthesis and Biological Evaluation of Aryl-phospho-indole as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

被引：167

作者：

Alexandre, Francois-Rene ^{[1
]}

Amador, Agnes ^{[1
]}

Bot, Stephanie ^{[1
]}

Caillet, Catherine ^{[1
]}

Convard, Thierry ^{[1
]}

Jakubik, Jocelyn ^{[3
]}

Musiu, Chiara ^{[2
]}

Poddesu, Barbara ^{[2
]}

Vargiu, Luana ^{[2
]}

Liuzzi, Michel ^{[2
]}

Roland, Arlene ^{[1
]}

Seifer, Maria ^{[3
]}

Standring, David ^{[3
]}

Storer, Richard ^{[1
]}

Dousson, Cyril B. ^{[1
]}

机构：

[1] Labs Idenix, Dept Chim Med, F-34189 Montpellier 4, France

[2] Univ Cagliari, Cooperat Lab Idenix, Zona Ind Macchiareddu UTA, Idenix Pharmaceut, I-09010 Cagliari, Italy

[3] Idenix Pharmaceut, Cambridge, MA 02139 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 01期

关键词：

ANALOGS; DESIGN; POTENT;

D O I：

10.1021/jm101142k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 3-aryl-phospho-indole (API) non-nucleoside reverse transcriptase inhibitors of HIV-1 was developed Chemical variation in the phosphorus linker led to the discovery of 3-phenyl-methyl-phosphinate-2-carboxamide 14, which possessed excellent potency against wild-type HIV-1 as well as viruses bearing K103N and Y181C single mutants in the reverse transcriptase gene Chiral separation of the enantiomers showed that only R enantiomer retained the activity The pharmacokinetic, solubility, and metabolic properties of 14 were assessed

引用

页码：392 / 395

页数：4

共 20 条

[1] PREPARATION AND REACTIONS OF 1-(TERT-BUTYLDIMETHYLSILYL)-3-LITHIOINDOLE, REGIOSELECTIVE SYNTHESIS OF 3-SUBSTITUTED INDOLES [J].

AMAT, M ;

HADIDA, S ;

SATHYANARAYANA, S ;

BOSCH, J .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (01) :10-11

[2]

[Anonymous], 2006, WO PCT Int. Appl., Patent No. 054182

[3] Non-nudeoside reverse transcriptase inhibitors - an overview [J].

Bell, C ;

Matthews, GV ;

Nelson, MR .

INTERNATIONAL JOURNAL OF STD & AIDS, 2003, 14 (02) :71-77

[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] From 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk](1,4)benzodiazepin-2(1H)-one (TIBO) to etravirine (TMC125):: Fifteen years of research on non-nucleoside inhibitors of HIV-1 reverse transcriptase [J].

De Corte, BL .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) :1689-1696

[6] SYNTHESIS AND NMR SPECTROSCOPIC INVESTIGATION OF PHENYLPHOSPHORYL DERIVATIVES [J].

DUDDECK, H ;

LECHT, R .

PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 1987, 29 (2-4) :169-178

[7] INFLUENCE OF ORTHO-METHYL AND ISOPROPYL SUBSTITUENTS ON THE REACTIVITY OF N-TERT-BUTYL P-ARYLPHOSPHONAMIDIC CHLORIDES WITH ISOPROPYLAMINE AND TERT-BUTYLAMINE - STERIC ACCELERATION OF METAPHOSPHONIMIDATE FORMATION BY AN ELIMINATION ADDITION MECHANISM - CONTRASTING BEHAVIOR OF N,N-DIMETHYL P-ARYLPHOSPHONAMIDIC CHLORIDES [J].

FREEMAN, S ;

HARGER, MJP .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1987, (06) :1399-1406

[8] Synthesis and antiviral evaluation of thieno[3,4-d] pyrimidine C-nucleoside analogues of 2′,3′-dideoxy- and 2′,3′-dideoxy-2′,3′-didehydro-adenosine and -inosine [J].

Hamann, Marie ;

Pierra, Claire ;

Sommadossi, Jean-Pierre ;

Musiu, Chiara ;

Vargiu, Luana ;

Liuzzi, Michel ;

Storer, Richard ;

Gosselin, Gilles .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (06) :2321-2326

[9] Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 1. [J].

Hopkins, AL ;

Ren, JS ;

Milton, J ;

Hazen, RJ ;

Chan, JH ;

Stuart, DI ;

Stammers, DK .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (24) :5912-5922

[10] Novel HIV-1 reverse transcriptase inhibitors [J].

Jochmans, Dirk .

VIRUS RESEARCH, 2008, 134 (1-2) :171-185

← 1 2 →