Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5].
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.
Bennett
Frank
F
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. frank.bennett@spcorp.com
Saksena
Anil K
AK
Lovey
Raymond G
RG
Liu
Yi-Tsung
YT
Patel
Naginbhai M
NM
Pinto
Patrick
P
Pike
Russel
R
Jao
Edwin
E
Girijavallabhan
Viyyoor M
VM
Ganguly
Ashit K
AK
Loebenberg
David
D
Wang
Haiyan
H
Cacciapuoti
Anthony
A
Moss
Eugene
E
Menzel
Fred
F
Hare
Roberta S
RS
Nomeir
Amin
A
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*
D000438:Alcohols; D000935:Antifungal Agents; D007166:Immunosuppressive Agents; C094161:SCH 51048; D014230:Triazoles; C101425:posaconazole