Synthesis of 2-phenylthiazolidine derivatives as cardiotonic agents. IV. Modification of the phenylpiperazino moiety of 2-(phenylpiperazinoalkoxyphenyl)thiazolidine-3-carbothioamides and the corresponding carboxamides
| Autor: | Akishige Watanabe, Yasushi Honma, Hiroshi Wada, Hiroyuki Nate, Isao H. Inoue, Mikihiko Konda, Hisao Ohtsuka, Takeshi Kanno, Hideo Yabana, Akihiko Ishida, Mikio Takeda, Hideo Nakai, Yasuo Sekine, Kuniyuki Oda, Taku Nagao, Kenji Matsuki |
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| Rok vydání: | 1987 |
| Předmět: |
Cardiotonic Agents
Chemical Phenomena Stereochemistry Ethylenediamines Thiazolidine General Chemistry General Medicine Piperazines Thioamides Chemistry Structure-Activity Relationship Thiazoles chemistry.chemical_compound Piperazine Dogs chemistry Amide Drug Discovery Alkoxy group Animals Moiety Structure–activity relationship Piperidine |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 35:2825-2839 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.35.2825 |
| Popis: | Examination of the structure-activity relationships of 2- (phenylpiperazinoalkoxyphenyl) -thiazolidine-3-carbothioamides and the corresponding carboxamides (1) as new cardiotonic agents was extended by the chemical modification of the phenylpiperazino moiety. The 4-phenylpiperidine (13), 4-phenyltetrahydropyridines (17), and related derivatives were prepared from the chlorides (10) through several intermediates (12, 14, and 16) and tested for cardiotonic activity. Generally, both the 4-phenylpiperidine (13) and 4-phenyltetrahydropyridine (17) derivatives exhibited potent positive inotropic activity comparable to that of 1. The N-phenylpiperidines (9) and amide derivatives (22, 25, and 28) exhibited no significant positive inotropy. This is also the case for the phenylpropylamines (29) and the ethylenediamines (30), which are pseudo-ring analogues of 1 with respect to the piperazine moiety. The activity of the homopiperazine derivative (23) was approximately one-thirtieth of that of the corresponding piperazine derivative (1). Thus, the presence of the six-membered, basic azacycloalkane ring (piperidine or piperazine) with a 4-phenyl group at the end of the alkoxy side chain appears to be essential for the appearance of potent positive inotropic activity in this series of compounds. |
| Databáze: | OpenAIRE |
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