Research on anti-HIV-1 agents. Part 2: Solid-phase synthesis, biological evaluation and molecular modeling studies of 2,5,6-trisubstituted-4(3H)-pyrimidinones targeting HIV-1 reverse transcriptase

被引：46

作者：

Botta, M

Corelli, F

Maga, G

Manetti, F

Renzulli, M

Spadari, S

机构：

[1] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy

[2] CNR, Ist Genet Biochim & Evoluzionist, I-27100 Pavia, Italy

来源：

TETRAHEDRON | 2001年 / 57卷 / 39期

关键词：

solid-phase synthesis; pyrimidinones; anti-HIV-1; agents; molecular docking;

D O I：

10.1016/S0040-4020(01)00815-8

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A small library of 2,6-disubstituted- and 2,5,6-trisubstituted-4(3H)-pyrimidinones has been synthesized by solid-phase synthesis starting from a modified Merrifield resin. The new pyrimidinones have been tested in vitro for their ability to inhibit HIV-1 RT in comparison with nevirapine. Interestingly, some of them showed moderate activity against recombinant RTs carrying mutations conferring resistance to TIBO/nevirapine. The possible mode of binding between Y188L mutant of RT and the new compounds has been studied through a molecular modeling approach. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：8357 / 8367

页数：11

共 38 条

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