Synthesis and biological evaluation of novel T-type calcium channel blockers.
作者： Ja Youn Choi , Han Na Seo , Min Joo Lee , Seong Jun Park , Sung Jun Park
DOI: 10.1016/J.BMCL.2006.10.024
关键词: Calcium channel 、 T-type calcium channel 、 Chemistry 、 Channel blocker 、 N-type calcium channel 、 Biological activity 、 Selectivity 、 Voltage-dependent calcium channel 、 Mibefradil 、 Stereochemistry
摘要: Abstract 3,4-Dihydroquinazoline analogues substituted by N-methyl-N-(5-pyrrolidinopentyl)amine at the 2-position were synthesized and their blocking effects evaluated for T- N-type calcium channels. Compound 11b (KYS05080), compared to mibefradil (IC50 = 1.34 ± 0.49 μM), was about 5-fold potent (IC50 = 0.26 ± 0.01 μM) T-type channel (α1G) its selectivity of T/N-type also improved (7.5 versus 1.4 mibefradil).
elsevier.com
sci-hub.se 参考文章(17)
Rosalind S-I. Chuang, Howard Jaffe, Leanne Cribbs, Edward Perez-Reyes, Kenton J. Swartz, Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nature Neuroscience. ,vol. 1, pp. 668- 674 ,(1998) , 10.1038/3669
Serguei S. Sidach, Isabelle M. Mintz, Kurtoxin, a gating modifier of neuronal high- and low-threshold ca channels. The Journal of Neuroscience. ,vol. 22, pp. 2023- 2034 ,(2002) , 10.1523/JNEUROSCI.22-06-02023.2002
Franck Jourdain, Mireille Caron, Jean Claude Pommelet, Rapid Synthesis Of Large Enaminolactams, A Novel Class Of Macrocycles Synthetic Communications. ,vol. 29, pp. 1785- 1799 ,(1999) , 10.1080/00397919908086167
L. Lacinova, Pharmacology of recombinant low-voltage activated calcium channels. Current Drug Targets - Cns & Neurological Disorders. ,vol. 3, pp. 105- 111 ,(2004) , 10.2174/1568007043482543
Seong Jun Park, Sung Jun Park, Min Joo Lee, Hyewhon Rhim, Yoonjee Kim, Jung-Ha Lee, Bong Young Chung, Jae Yeol Lee, Synthesis and SAR studies of a novel series of T-type calcium channel blockers. Bioorganic & Medicinal Chemistry. ,vol. 14, pp. 3502- 3511 ,(2006) , 10.1016/J.BMC.2006.01.005
Munikumar Reddy Doddareddy, Hee Kyung Jung, Jae Yeol Lee, Yong Sup Lee, Yong Seo Cho, Hun Yeong Koh, Ae Nim Pae, First pharmacophoric hypothesis for T-type calcium channel blockers. Bioorganic & Medicinal Chemistry. ,vol. 12, pp. 1605- 1611 ,(2004) , 10.1016/J.BMC.2004.01.034
Jung-Ha Lee, Juan Carlos Gomora, Leanne L. Cribbs, Edward Perez-Reyes, Nickel Block of Three Cloned T-Type Calcium Channels: Low Concentrations Selectively Block α1H Biophysical Journal. ,vol. 77, pp. 3034- 3042 ,(1999) , 10.1016/S0006-3495(99)77134-1
Puay-Wah Phuan, Marisa C. Kozlowski, Control of the conformational equilibria in aza-cis-decalins: structural modification, solvation, and metal chelation. Journal of Organic Chemistry. ,vol. 67, pp. 6339- 6346 ,(2002) , 10.1021/JO025544T
Michael J Robarge, Stephen M Husbands, Andrzej Kieltyka, Robbin Brodbeck, Andrew Thurkauf, Amy Hauck Newman, None, Design and synthesis of [(2,3-dichlorophenyl)piperazin-1-yl]alkylfluorenylcarboxamides as novel ligands selective for the dopamine D3 receptor subtype. Journal of Medicinal Chemistry. ,vol. 44, pp. 3175- 3186 ,(2001) , 10.1021/JM010146O
Philipp Eller, Stanislav Berjukov, Siegmund Wanner, Irene Huber, Steffen Hering, Hans-Günther Knaus, Geza Toth, S David Kimball, Jörg Striessnig, High affinity interaction of mibefradil with voltage-gated calcium and sodium channels British Journal of Pharmacology. ,vol. 130, pp. 669- 677 ,(2000) , 10.1038/SJ.BJP.0703352