title: Novel indole based NNRTIs with improved potency against wild type and resistant HIV.
abstract: The human immunodeficiency virus (HIV) pandemic remains a significant problem, especially in developing nations where the social and economic impacts are severe. Until a cure or vaccine for the disease is found, a constant supply of new compounds to fill the drug development pipeline is a requirement, given the tendency for the virus to rapidly develop resistance to current therapies. Here we disclose our efforts to improve upon the efficacy of cyclopropyl-indole derivatives developed as NNRTIs in our laboratories. To this end, modifications to the functionality occupying the small Val179 pocket have resulted in nearly two orders of magnitude increase in potency.
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Ronel
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Mulani
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, 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: Nicole
authors.initials: N
authors.lastname: Pribut
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape, South Africa.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hassam
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa.
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
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: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; C030374:indole; D054303:HIV Reverse Transcriptase
keywords: AIDS; HIV; Indole; NNRTIs