OPTICALLY-ACTIVE ANTIFUNGAL AZOLES .7. SYNTHESIS AND ANTIFUNGAL ACTIVITY OF STEREOISOMERS OF TRAFLUOROPROPOXY)PHENYL]-3(2H,4H)-1,2,4-TRIAZOLONE (TAK-187)

trafluoropropoxy)phenyl]-3(2H,4H)-1,2,1-triazolone [(1R,2R)-1: TAK-187 ] is a new antifungal agent selected as a candidate for clinical trial s, The three stereoisomers [(1S,2S)-, (1R,2S)- and (1S,2R)-1] of this compound were prepared to clarify the relationship between the stereoc hemistry and the biological activities, In vitro and in vivo assays of antifungal activity revealed that TAK-187 [(1R,2R)-1] is the most pot ent among the four stereoisomers. Furthermore, TAK-187 was found to ex ert a strong and selective inhibitory effect on the sterol synthesis i n Candida albicans as compared with that in rat liver.