| Autor: |
Romero DL; Upjohn Laboratories, Kalamazoo, Michigan 49001., Morge RA, Biles C, Berrios-Pena N, May PD, Palmer JR, Johnson PD, Smith HW, Busso M, Tan CK, et. al. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1994 Apr 01; Vol. 37 (7), pp. 999-1014. |
| DOI: |
10.1021/jm00033a018 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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