153473-49-5Relevant articles and documents
Indoles and pyridazinoindoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase
Font, M.,Monge, A.,Cuartero, A.,Ellorriaga, A.,Martinez-Irujo, J.J.,et al.
, p. 963 - 972 (2007/10/03)
The synthesis and the study of the activity of new indol-2-carboxamides and pyridazinoindoles as inhibitors of HIV-1 reverse transcriptase (RT) are presented.The activity of the compounds synthesized as inhibitors of different types of HIV-1 RT (wild type enzyme and mutant forms P236L, Y181C and P236L/Y181C) was evaluated.The activity of the most active compounds was investigated in the syncytia reduction in vitro assay, in HIV-1IIIB-infected HT4lacZ-1 cells.Their potential cytotoxicity was determined in parallel.Two lead compounds,N-piperazin>-5,6-methylenedioxy indol-2-carboxamide 7q and N-piperazin>-5,6-methylenedioxyindol-2-carboxamide 7s have been identified. - Keywords: indole; nonnucleoside RT inhibitor; syncytia assay; HIV-1IIIBHT4lacZ-1 cells
Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors
Romero,Morge,Biles,Berrios-Pena,May,Palmer,Johnson,Smith,Busso,Tan,Voorman,Reusser,Althaus,Downey,So,Resnick,Tarpley,Aristoff
, p. 999 - 1014 (2007/10/02)
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.
