First pharmacophoric hypothesis for T-type calcium channel blockers.
A three-dimensional pharmacophore model was developed for T-type calcium channel blockers in order to map common structural features of highly active compounds by using CATALYST program. In the absence of three dimensional structure based information like binding mode and unavailability of more number of specific T-type calcium channel blockers, this hypothesis which consists of three hydrophobic regions, one hydrogen bond acceptor and one positive ionizable regions will act as a valuable tool in designing new ligands. Further more after the withdrawal of mibefradil, the first marketed T-type calcium channel blocker, due to the drug-drug interactions, there is an urgent need for more work in this interest.
Doddareddy
Munikumar Reddy
MR
Biochemicals Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, South Korea.
Jung
Hee Kyung
HK
Lee
Jae Yeol
JY
Lee
Yong Sup
YS
Cho
Yong Seo
YS
Koh
Hun Yeong
HY
Pae
Ae Nim
AN
D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015195:Drug Design; D004347:Drug Interactions; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D008024:Ligands