Synthesis of 2-phenylthiazolidine derivatives as cardiotonic agents. III. Optically active isomers of N-methyl-2-(2-(2-(4-phenylpiperazino)ethoxy)phenyl)thiazolidine-3-carboxamides.
-
- NATE HIROYUKI
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- SEKINE YASUO
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- ODA KUNIYUKI
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- AOE KEIICHI
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- NAKAI HIDEO
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- WADA HIROSHI
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- TAKEDA MIKIO
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- KOTERA KEISHI
- Organic Chemistry Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- YABANA HIDEO
- Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
-
- NAGAO TAKU
- Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
説明
Optically active isomers of N-methyl-2- (2- (2- (4-phenylpiperazino) ethoxy) phenyl) thiazolidine-3-carboxamides ((+) -2 and (-) -2) have been synthesized and tested for positive inotropic activity. The racemic thiocarboxamide ((±) -3) was resolved into the enantiomers ((+) -3 and (-) -3) via the L-and D-N- (2-naphthylsulfonyl) prolyl derivatives ((+) -4 and (-) -4). Conversion of the thiocarboxamides ((+) -3 and (-) -3) to the carboxamides ((+) -2 and (-) -2) was smoothly effected by treatment with the glycidic ester (7). The absolute stereochemistry of (-) -3 was determined to be 2S by X-ray crystallographic analysis. Hence, the absolute configuration of the carboxamide ((-) -2) is 2S. On i.v. administration to anesthetized dogs, the enantiomers of 2 showed only a threefold difference in positive inotropic activity, with the levo isomer ((-) -2) being the more active. In the isolated cat heart muscle, the enantiomers were nearly equipotent to each other. Thus, no significant difference between the positive inotropic activities of the optical isomers of 2 was observed.
収録刊行物
-
- CHEMICAL & PHARMACEUTICAL BULLETIN
-
CHEMICAL & PHARMACEUTICAL BULLETIN 35 (6), 2412-2418, 1987
公益社団法人 日本薬学会