Synthesis and biological evaluation of novel T-type calcium channel blockers

  • Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5. doi: 10.1016/j.bmcl.2006.10.024.
Ja Youn Choi  1 ,  Han Na Seo ,  Min Joo Lee ,  Seong Jun Park ,  Sung Jun Park ,  Ji Young Jeon ,  Joo Hi Kang ,  Ae Nim Pae ,  Hyewhon Rhim ,  Jae Yeol Lee
Affiliations
  • 1. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 1 Hoegi-Dong, Seoul 130-701, Republic of Korea.
PMID: 17064894 DOI: 10.1016/j.bmcl.2006.10.024
Abstract

3,4-Dihydroquinazoline analogues substituted by N-methyl-N-(5-pyrrolidinopentyl)amine at the 2-position were synthesized and their blocking effects were evaluated for T- and N-type calcium channels. Compound 11b (KYS05080), compared to mibefradil (IC50=1.34+/-0.49 microM), was about 5-fold potent (IC50=0.26+/-0.01 microM) for T-type calcium channel (alpha1G) blocking and its selectivity of T/N-type was also improved (7.5 versus 1.4 of mibefradil).