Betulinic acid derivatives: A new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action

被引：130

作者：

Evers, M

Poujade, C

Soler, F

Ribeill, Y

James, C

Lelievre, Y

Gueguen, JC

Reisdorf, D

Morize, I

Pauwels, R

DeClercq, E

Henin, Y

Bousseau, A

Mayaux, JF

LePecq, JB

Dereu, N

机构：

[1] RHONE POULENC RORER SA,CTR RECH VITRY ALFORTVILLE,DEPT BIOL,F-94403 VITRY,FRANCE

[2] RHONE POULENC RORER SA,CTR RECH VITRY ALFORTVILLE,DEPT BIOTECHNOL,F-94403 VITRY,FRANCE

[3] KATHOLIEKE UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 05期

关键词：

D O I：

10.1021/jm950670t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3 beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C). oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

引用

页码：1056 / 1068

页数：13

共 28 条

[1] POTENT AND SELECTIVE-INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) BY 5-ETHYL-6-PHENYLTHIOURACIL DERIVATIVES THROUGH THEIR INTERACTION WITH THE HIV-1 REVERSE-TRANSCRIPTASE [J].