title: Pyrazole NNRTIs 4: selection of UK-453,061 (lersivirine) as a development candidate.
abstract: We prepared three discreet cohorts of potent non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) based on the recently reported 3-cyanophenoxypyrazole lead 3. Several of these compounds displayed very promising anti-HIV activity in vitro, safety, pharmacokinetic and pharmaceutical profiles. We describe our analysis and conclusions leading to the selection of alcohol 5 (UK-453,061, lersivirine) for clinical development.
authors.affiliation: Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK. Charles.Mowbray@Pfizer.Com
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mowbray
authors.forename: Catherine
authors.initials: C
authors.lastname: Burt
authors.forename: Romuald
authors.initials: R
authors.lastname: Corbau
authors.forename: Simon
authors.initials: S
authors.lastname: Gayton
authors.forename: Michael
authors.initials: M
authors.lastname: Hawes
authors.forename: Manos
authors.initials: M
authors.lastname: Perros
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tran
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Faye J
authors.initials: FJ
authors.lastname: Quinton
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: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D002460:Cell Line; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011720:Pyrazoles; D018894:Reverse Transcriptase Inhibitors; C531151:UK 453,061; D054303:HIV Reverse Transcriptase