title: Novel indole sulfides as potent HIV-1 NNRTIs.
abstract: 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.
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Brigg
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pribut
authors.affiliation: National Institute for Communicable Diseases, Centre for HIV and STI: HIV Virology Section, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Adriaan E
authors.initials: AE
authors.lastname: Basson
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Moscos
authors.initials: M
authors.lastname: Avgenikos
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Reinhardt
authors.initials: R
authors.lastname: Venter
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Blackie
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Willem A L
authors.initials: WAL
authors.lastname: van Otterlo
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa. Electronic address: scpelly@sun.ac.za.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pelly
mesh_terms: D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects* / Q000201:enzymology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013440:Sulfides; D054303:HIV Reverse Transcriptase
keywords: HIV; Indole; NNRTI; Sulfides