Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers.
A small molecule library of 1,3-dioxoisoindoline-5-carboxamides 4 was designed based on the pharmacophore model, synthesized and biologically evaluated as potential T-type calcium channel blockers. The most active compounds 4d and 4n show T-type calcium channel blocking activity with IC50 values of 0.93 and 0.96 microM, respectively.
Kim
Hwa Sil
HS
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Kim
Yoonjee
Y
Doddareddy
Munikumar Reddy
MR
Seo
Seon Hee
SH
Rhim
Hyewhon
H
Tae
Jinsung
J
Pae
Ae Nim
AN
Choo
Hyunah
H
Cho
Yong Seo
YS
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D002460:Cell Line; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology; D008958:Models, Molecular; D018408:Patch-Clamp Techniques
C518624:1,3-dioxoisoindoline-5-carboxamide; D000577:Amides; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D007202:Indicators and Reagents; D007211:Indoles; D020748:Mibefradil