| Autor: |
Kiyomi Yamatsu, Hiroyuki Sugumi, Yutaka Tsuchiya, Atsushi Sasaki, Kunizo Higurashi, Yoshiharu Yamanishi, Norio Karibe, Hachiro Sugimoto, Shin Araki, Yoichi Iimura |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
ChemInform. 25 |
| ISSN: |
0931-7597 |
| DOI: |
10.1002/chin.199410176 |
| Popis: |
Following the discovery of a new series of 1-benzyl-4-[2-(N-benzoyl-N-methylamino)ethyl]piperidine (2) derivatives with a potent anti-acetylcholinesterase (anti-AChE) activity, we extended the structure-activity relationships (SAR) to rigid analogues (4) and 1-benzyl-4-[2-(N-benzoyl-N-phenylamino)ethyl]piperidine derivatives (3). Introduction of a phenyl group on the nitrogen atom of the amide moieties resulted in enhanced activity. The rigid analogue containing isoindolone (9) was found to exhibit potent anti-AChE activity comparable to that of 2. Furthermore, replacement of the isoindolone with other heterobicyclic ring systems was examined. Among the compounds prepared in these series, 1-benzyl-4-[2-[4-(benzoylamino)phthalimido]ethyl]piperidine hydrochloride (19) (IC50 = 1.2 nM) is one of the most potent inhibitors of AChE. Compound 19 showed a definite selectivity to AChE over the BuChE (about 34700-fold) and, at dosages of 10-50 mg/kg, exerted a dose-dependent inhibitory effect on AChE in rat brain. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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