title: Core chemotype diversification in the HIV-1 entry inhibitor class using field-based bioisosteric replacement.
abstract: Demand remains for new inhibitors of HIV-1 replication and the inhibition of HIV-1 entry is an extremely attractive therapeutic approach. Using field-based bioisosteric replacements, we have further extended the chemotypes available for development in the HIV-1 entry inhibitor class. Moreover, using field-based disparity analysis of the compounds, 3D structure-activity relationships were derived that will be useful in the further development of these inhibitors towards clinical utility.
authors.affiliation: Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Rooms 10302-10306, 245 N. 15th Street, Philadelphia, PA 19102, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Tuyishime
authors.affiliation: Cresset, New Cambridge House, Bassingbourn Road, Litlington, Cambridgeshire, UK.
authors.forename: Rae
authors.initials: R
authors.lastname: Lawrence
authors.affiliation: Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Rooms 10302-10306, 245 N. 15th Street, Philadelphia, PA 19102, USA. Electronic address: scocklin@drexelmed.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: Cocklin
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D055672:Static Electricity; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents
keywords: Antiviral; Bioisosteric replacement; Computer-aided drug design; Field-based; HIV-1 envelope protein; SAR analysis; Scaffold-hopping; Structure–activity landscape