Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers.
Morpholin-2-one-5-carboxamide derivatives were prepared by using the one-pot Ugi multicomponent reaction and evaluated for blocking effects on T- and N-type Ca(2+) channels. Among them, compound 5i produced the highest potency (IC(50)=0.45+/-0.02 microM), while compounds 5d, 5f, 5k, 5n, 5o, and 6m produced relatively high potency as well as selectivity on T-type Ca(2+) channels. These novel scaffolds showed potent and selective T-type Ca(2+) channel blocking activities.
Ku
Il Whea
IW
Life Sciences Division, Korea Institute of Science and Technology, KIST, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
Cho
Sangwon
S
Doddareddy
Munikumar Reddy
MR
Jang
Min Seok
MS
Keum
Gyochang
G
Lee
Jung-Ha
JH
Chung
Bong Young
BY
Kim
Youseung
Y
Rhim
Hyewhon
H
Kang
Soon Bang
SB
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology*; D009865:Oocytes; D013329:Structure-Activity Relationship; D014981:Xenopus
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D009025:Morpholines