Novel indole sulfides as potent HIV-1 NNRTIs.

Autor: Brigg S; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa., Pribut N; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa., Basson AE; National Institute for Communicable Diseases, Centre for HIV and STI: HIV Virology Section, Private Bag X4, Sandringham, Johannesburg 2131, South Africa., Avgenikos M; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa., Venter R; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa., Blackie MA; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa., van Otterlo WAL; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa., Pelly SC; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa. Electronic address: scpelly@sun.ac.za.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Mar 15; Vol. 26 (6), pp. 1580-1584. Date of Electronic Publication: 2016 Feb 04.
DOI: 10.1016/j.bmcl.2016.02.006
Abstrakt: In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted SN1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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