Novel indole sulfides as potent HIV-1 NNRTIs
| Autor: | Adriaan E. Basson, Margaret A.L. Blackie, Siobhan Brigg, Willem A. L. van Otterlo, Moscos Avgenikos, Stephen C. Pelly, Nicole Pribut, Reinhardt Venter |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Indoles Stereochemistry Clinical Biochemistry Pharmaceutical Science Ether Sulfides Virus Replication 01 natural sciences Biochemistry Virus 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Potency Structure–activity relationship Molecular Biology Indole test Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Wild type virus diseases HIV Reverse transcriptase HIV Reverse Transcriptase 0104 chemical sciences 030104 developmental biology Viral replication Molecular Medicine Reverse Transcriptase Inhibitors |
| Zdroj: | Bioorganicmedicinal chemistry letters. 26(6) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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