DISCOVERY, SYNTHESIS, AND BIOACTIVITY OF BIS(HETEROARYL)PIPERAZINES .1. A NOVEL CLASS OF NONNUCLEOSIDE HIV-1 REVERSE-TRANSCRIPTASE INHIBITORS

被引：99
作者：
ROMERO, DL
MORGE, RA
BILES, C
BERRIOSPENA, TN
MAY, PD
PALMER, JR
JOHNSON, PD
SMITH, HW
BUSSO, M
TAN, CK
VOORMAN, RL
REUSSER, F
ALTHAUS, IW
DOWNEY, KM
SO, AG
RESNICK, L
TARPLEY, WG
ARISTOFF, PA
机构：
[1] MT SINAI MED CTR,MIAMI BEACH,FL 33140
[2] UNIV MIAMI,MIAMI,FL 33101
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 07期
关键词：
D O I：
10.1021/jm00033a018
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A variety of analogues of 1-[4-methoxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2-pyridyl]piperazine hydrochloride (U-80493E) were synthesized and evaluated for their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Replacement of the substituted aryl moiety with various substituted indoles provided bis(heteroaryl)piperazines (BHAPs) that were 10-100-fold more potent than U-80493E. The pyridyl portion of the lead molecule was found to be very sensitive to modifications. Extensive preclinical evaluations of several of these compounds led to the selection of 1-[(5-methoxyindol-2-yl)carbonyl]-4-[3-(ethylamino)-2-pyridyl]piperazine methanesulfonate (U-87201E, atevirdine mesylate) for clinical evaluation.
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页码：999 / 1014
页数：16
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