DISCOVERY, SYNTHESIS, AND BIOACTIVITY OF BIS(HETEROARYL)PIPERAZINES .1. A NOVEL CLASS OF NONNUCLEOSIDE HIV-1 REVERSE-TRANSCRIPTASE INHIBITORS
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 va...
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Published in | Journal of medicinal chemistry Vol. 37; no. 7; pp. 999 - 1014 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
Amer Chemical Soc
01.04.1994
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Subjects | |
Online Access | Get full text |
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Summary: | 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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ISSN: | 0022-2623 |
DOI: | 10.1021/jm00033a018 |