新型T型钙通道阻滞剂的合成与生物学评价
Synthesis and biological evaluation of novel T-type calcium channel blockers.
作者信息
Choi Ja Youn, Seo Han Na, Lee Min Joo, Park Seong Jun, Park Sung Jun, Jeon Ji Young, Kang Joo Hi, Pae Ae Nim, Rhim Hyewhon, Lee Jae Yeol
机构信息
Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, 1 Hoegi-Dong, Seoul 130-701, Republic of Korea.
出版信息
Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5. doi: 10.1016/j.bmcl.2006.10.024. Epub 2006 Oct 12.
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).
合成了在2位被N-甲基-N-(5-吡咯烷基戊基)胺取代的3,4-二氢喹唑啉类似物，并评估了它们对T型和N型钙通道的阻断作用。与米贝拉地尔（IC50 = 1.34±0.49微摩尔）相比，化合物11b（KYS05080）对T型钙通道（α1G）的阻断效力约高5倍（IC50 = 0.26±0.01微摩尔），并且其T/N型选择性也有所提高（米贝拉地尔为1.4，而该化合物为7.5）。
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