title: Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5].
abstract: As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. frank.bennett@spcorp.com
authors.forename: Frank
authors.initials: F
authors.lastname: Bennett
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saksena
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Lovey
authors.forename: Yi-Tsung
authors.initials: YT
authors.lastname: Liu
authors.forename: Naginbhai M
authors.initials: NM
authors.lastname: Patel
authors.forename: Patrick
authors.initials: P
authors.lastname: Pinto
authors.forename: Russel
authors.initials: R
authors.lastname: Pike
authors.forename: Edwin
authors.initials: E
authors.lastname: Jao
authors.forename: Viyyoor M
authors.initials: VM
authors.lastname: Girijavallabhan
authors.forename: Ashit K
authors.initials: AK
authors.lastname: Ganguly
authors.forename: David
authors.initials: D
authors.lastname: Loebenberg
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Cacciapuoti
authors.forename: Eugene
authors.initials: E
authors.lastname: Moss
authors.forename: Fred
authors.initials: F
authors.lastname: Menzel
authors.forename: Roberta S
authors.initials: RS
authors.lastname: Hare
authors.forename: Amin
authors.initials: A
authors.lastname: Nomeir
mesh_terms: D000438:Alcohols; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy; D002177:Candidiasis / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D000882:Haplorhini; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008956:Models, Chemical; D013997:Time Factors; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000438:Alcohols; D000935:Antifungal Agents; D007166:Immunosuppressive Agents; C094161:SCH 51048; D014230:Triazoles; C101425:posaconazole