N′-[2-(2-thiophene)ethyl]-N′-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1

被引：64

作者：

Uckun, FM ^{[1
]}

Pendergrass, S

Maher, D

Zhu, D

Tuel-Ahlgren, L

Mao, C

Venkatachalam, TK

机构：

[1] Hughes Inst, Drug Discovery Program, Dept Chem, St Paul, MN 55113 USA

[2] Hughes Inst, Dept Virol, St Paul, MN 55113 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(99)00624-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The thiophene-ethyl thiourea (TET) compound N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridl)]-thiourea (compound HI-443) was five times more potent than trovirdine, 1250 times more potent than nevirapine, 100 times more potent than delavirdine, 75 times more potent than MKC-442, and 50 times more potent than AZT against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation. HI-443 was almost as potent against the NNI-resistant HIV-I strain A17 with a Y181C mutation as it was against HTLVIIIB. The activity of HI-443 against A17 was ten times more potent than that of trovirdine, 2083 times more potent than that of nevirapine, and 1042 times more potent than that of delavirdine. HI-443 inhibited the replication of the NNI-resistant HIV-1 strain A17 variant with Y181C plus K103N mutations in RT with an IC, value of 3.3 mu M, whereas the IC50 values of trovirdine, nevirapine, and delavirdine were all >100 mu M. These findings establish the novel thiophene containing thiourea compound HI-443 as a novel NNI with potent antiviral activity against NNI-sensitive, NNI-resistant and multidrug-resistant strains of HIV-l. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：3411 / 3416

页数：6

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