Synthesis and biological evaluation of 1,4-diazepane derivatives as T-type calcium channel blockers.
We have synthesized and biologically evaluated 1,4-diazepane derivatives as T-type calcium channel blockers. In this study, we discovered compound 4s, a potential T-type calcium channel blocker with good selectivity over hERG and N-type calcium channels. In addition, it exhibited favorable pharmacokinetic characteristics for further investigation of T-type calcium channel related diseases.
Gu
Su Jin
SJ
Life/Health Division, Korea Institute of Science and Technology, PO Box 131, Cheongyang, Seoul 130-650, Republic of Korea.
Lee
Jae Kyun
JK
Pae
Ae Nim
AN
Chung
Hye Jin
HJ
Rhim
Hyewon
H
Han
So Yeob
SY
Min
Sun-Joon
SJ
Cho
Yong Seo
YS
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D020747:Calcium Channels, T-Type / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
C545228:1,4-diazepane; D000959:Antihypertensive Agents; D001381:Azepines; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG