Synthesis and antifungal activity of the 2,2,5-tetrahydrofuran regioisomers of SCH 51048.
The four 2,2,5-regioisomer counterparts of SCH 51048 were synthesized and evaluated. As with the parent series, only the two cis isomers possessed any in vitro activity, and only the activity of the isomer with the R-configuration at the tetrahydrofuran 2-carbon was significant. The activity data suggests that oxygen at only one of the two possible ring positions benzylic to the difluorobenzene participates usefully in active site binding.
Lovey
Raymond G
RG
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. raymond.lovey@spcorp.com
Saksena
Anil K
AK
Girijavallabhan
Viyyoor M
VM
Blundell
Paul
P
Guzik
Henry
H
Loebenberg
David
D
Parmegiani
Raulo M
RM
Cacciapuoti
Anthony
A
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001554:Benzene / Q000737:chemistry; D001665:Binding Sites; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology
D000935:Antifungal Agents; D005663:Furans; C094161:SCH 51048; D014230:Triazoles; C018674:tetrahydrofuran; D001554:Benzene; D010100:Oxygen