Journal of Medicinal Chemistry p. 2504 - 2511 (1986)
Update date:2022-09-26
Topics:
Tamazawa, Kazuharu
Arima, Hideki
Koijma, Tadao
Isomura, Yasuo
Okada, Minoru
et al.
Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). <3H>Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated.The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a*HBr as well as 3a*HCl.The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation.The potency order of the four enantiomers was (S,S)-3a > (S,R)-3b > (R,R)-3d > (R,S)-3c.Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a*HCl or 3a*HBr.On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5.The conformational restriction may be a factor causing stereoselectivity of antagonism.
View MoreContact:86-310-8067016
Address:East Fuhua Road,Tiexi Chemical Industrial Estate,Hebei,China
Suzhou Wedo Chemicals Co., Ltd.
Contact:86 512 58100425
Address:Zonger Road, DongSha Industry Park , Zhangjiagang, Jiangsu, China
website:http://www.simagchem.com
Contact:+86-592-2680277
Address:21/F Hualong Office Building,No.6 Hubin East Road, Xiamen,China
Hangzhou Zyter Biological & Chemical Technology Co., Ltd.
website:http://www.zyterpharm.com
Contact:+86-18858184290
Address:West Wenyi Road, Cangqian, Yuhang
Shanghai Puda Chemical Co.,Ltd
Contact:+86+571+56565965
Address:10F Haiyue Building,Danfeng Road,Binjiang District,Hangzhou,China
Doi:10.1007/BF00473842
()Doi:10.1039/c7gc01449j
(2017)Doi:10.1016/S0022-328X(00)00911-6
(2001)Doi:10.1016/S0040-4039(01)86357-7
(1979)Doi:10.1039/c39790000975
(1979)Doi:10.1021/acs.joc.5b00474
(2015)