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

Authors
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
Citation
Dl. Romero et al., DISCOVERY, SYNTHESIS, AND BIOACTIVITY OF BIS(HETEROARYL)PIPERAZINES .1. A NOVEL CLASS OF NONNUCLEOSIDE HIV-1 REVERSE-TRANSCRIPTASE INHIBITORS, Journal of medicinal chemistry, 37(7), 1994, pp. 999-1014
Citations number
61
Categorie Soggetti
Chemistry Medicinal
Journal title
Journal of medicinal chemistry → ACNP
ISSN journal
00222623
Volume
37
Issue
7
Year of publication
1994
Pages
999 - 1014
Database
ISI
SICI code
0022-2623(1994)37:7<999:DSABOB>2.0.ZU;2-I
Abstract
A variety of analogues of thylbenzyl]-4-[3-(ethylamino)-2-pyridyl]pipe razine hydrochloride (U-80493E) were synthesized and evaluated for the ir inhibition of human immunodeficiency virus type 1 (HIV-1) reverse t ranscriptase (RT). Replacement of the substituted aryl moiety with var ious substituted indoles provided bis(heteroaryl)piperazines (BHAPs) t hat were 10-100-fold more potent than U-80493E. The pyridyl portion of the lead molecule was found to be very sensitive to modifications. Ex tensive preclinical evaluations of several of these compounds led to t he selection of l)carbonyl]-4-[3-(ethylamino)-2-pyridyl]piperazine met hanesulfonate (U-87201E, atevirdine mesylate) for clinical evaluation.