Synthesis of 2-phenylthiazolidine derivatives as cardiotonic agents. II. 2-(Phenylpiperazinoalkoxyphenyl)thiazolidine-3-thiocarboxamides and the corresponding carboxamides
| Autor: | Hisao Ohtsuka, Taku Nagao, Kuniyuki Oda, Yutaka Hino, Hiroshi Wada, Mikio Takeda, Akira Tsunashima, Hideo Nakai, Hiroyuki Nate, Yasuo Sekine, Kenji Matsuki, Akihiko Ishida, Yasushi Honma, Hideo Yabana |
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| Rok vydání: | 1987 |
| Předmět: |
Cardiotonic Agents
Chemical Phenomena Stereochemistry 2-phenylthiazolidine Thiazolidine Thio General Chemistry General Medicine Amides Amrinone Thioamides Chemistry Structure-Activity Relationship chemistry.chemical_compound Dogs chemistry Salicylaldehyde Drug Discovery medicine Alkoxy group Animals Structure–activity relationship medicine.drug |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 35:2394-2411 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.35.2394 |
| Popis: | A large number of 2- (phenylpiperazinoalkoxyphenyl) thiazolidine-3-thiocarboxamides and the corresponding carboxamides (II) were synthesized and tested for inotropic activity in anesthetized dogs. Compounds II were prepared from a hydroxybenzaldehyde (III) through the intermediates (IV, V, and X). Structure-activity relationships (SAR) were investigated by varying the structural parameters. Transposition of the piperazinoalkoxyl group to the meta or para position from the ortho position caused a marked fall in activity. Conversion of the thiocarboxamido to a carboxamido group caused a marked increase in activity. This tendency was generally observed in this series of compounds and constitutes a major deviation from the SAR in the simple 2-phenylthiazolidine series. With regard to effects of the length of the aminoalkoxy chain, the ethoxy derivatives were generally more potent than higher analogues. Lengthening of the N-alkyl group in the (thio) carboxamido group generally caused a decrease in activity. Among the various derivatives synthesized, II15 was found to be approximately one hundred times more potent than amrinone with a long duration of action. |
| Databáze: | OpenAIRE |
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