Asymmetric synthesis and biological evaluations of (+)- and (-)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels |
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Authors: | Yamamoto Takashi Ohno Seiji Niwa Seiji Tokumasu Munetaka Hagihara Masako Koganei Hajime Fujita Shin-ichi Takeda Tomoko Saitou Yuki Iwayama Satoshi Takahara Akira Iwata Seinosuke Shoji Masataka |
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Institution: | Exploratory Research Laboratories, Ajinomoto Pharmaceuticals Co., Ltd, 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa, Japan |
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Abstract: | An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of l-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (−)- and racemic isomers. |
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Keywords: | N-type calcium channel blocker Structure-activity relationships 1 4-Dihydropyridine derivative Asymmetric synthesis |
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