title: Pyrazole NNRTIs 3: optimisation of physicochemical properties.
abstract: Our efforts to reduce overall lipophilicity and increase ligand-lipophilicity efficiency (LLE) by modification of the 3- and 5-substituents of pyrazole 1, a novel non-nucleoside HIV reverse transcriptase inhibitor (NNRTI) prototype were unsuccessful. In contrast replacement of the substituted benzyl group with corresponding phenylthio or phenoxy groups resulted in marked improvements in potency, ligand efficiency (LE) and LLE.
authors.affiliation: Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent CT 13 9NJ, UK. Charles.Mowbray@Pfizer.com
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mowbray
authors.forename: Romuald
authors.initials: R
authors.lastname: Corbau
authors.forename: Michael
authors.initials: M
authors.lastname: Hawes
authors.forename: Lyn H
authors.initials: LH
authors.lastname: Jones
authors.forename: James E
authors.initials: JE
authors.lastname: Mills
authors.forename: Manos
authors.initials: M
authors.lastname: Perros
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Selby
authors.forename: Paul A
authors.initials: PA
authors.lastname: Stupple
authors.forename: Rob
authors.initials: R
authors.lastname: Webster
authors.forename: Anthony
authors.initials: A
authors.lastname: Wood
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055598:Chemical Phenomena; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D011720:Pyrazoles; D018894:Reverse Transcriptase Inhibitors; C031280:pyrazole; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase