Design and SAR of selective T-type calcium channel antagonists containing a biaryl sulfonamide core.
T-type calcium channel antagonists were designed using a protocol involving the program SPROUT and constrained by a ComFA-based pharmacophore model. Scaffolds generated by SPROUT were evaluated based on their ability to be translated into structures that were synthetically tractable. From this exercise, a novel series of potent and selective T-type channel antagonists containing a biaryl sulfonamide core were discovered.
Hangeland
Jon J
JJ
Bristol-Myers Squibb R& D, Princeton, NJ 08543-5400, USA. jon.hangeland@bms.com
Cheney
Daniel L
DL
Friends
Todd J
TJ
Swartz
Stephen
S
Levesque
Paul C
PC
Rich
Adam J
AJ
Sun
Lucy
L
Bridal
Terry R
TR
Adam
Leonard P
LP
Normandin
Diane E
DE
Murugesan
Natesan
N
Ewing
William R
WR
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D018360:Crystallography, X-Ray; D015195:Drug Design; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D013449:Sulfonamides