Synthesis, structure and muscarinic agonist activity of substituted N-(silatran-1-ylmethyl)acetamides

• Published in: Applied organometallic chemistry 2010-03, Vol.24 (3), p.162-168
• Main Authors: Pukhalskaya, Vera G., Kramarova, Eugeniya P., Kozaeva, Larisa P., Korlyukov, Alexander A., Shipov, Alexander G., Bylikin, Sergey Yu, Negrebetsky, Vadim V., Poryadin, Gennady V., Baukov, Yuri I.
• Format: Article
• Language: English
• Subjects: guinea pig ileum contraction; muscarinic agonist activity; silatranes; X-ray diffraction study
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.1539

Substituted N‐(silatran‐1‐ylmethyl)acetamides, N‐methyl‐N‐[1‐(3′,7′,10′‐trimethylsilatran‐1‐yl)methyl]acetamide (2a) and N‐(2‐hydroxyethyl)‐N‐[1‐(3′,7′,10′‐trimethylsilatran‐1‐yl)methyl]acetamide (2b) were prepared by the reactions of triisopropanolamine with N‐methyl‐N‐(trimethoxysilylmethyl)acetamide (1a) and 2,2‐dimethoxy‐4‐acetyl‐1‐oxa‐4‐aza‐2‐silacyclohexane (1b), respectively. According to X‐ray data, the structures of the silatrane moieties are superpositions of unsymmetrical and symmetrical stereoisomers. The O → Si coordination between the central atom and exocyclic substituent is absent in both compounds. Silatranes 2a and 2b are partial muscarinic agonists which demonstrate submaximal effect and mimic the effect of acetylcholine by binding directly to cholinoreceptors of the ileal smooth muscle. Copyright © 2009 John Wiley & Sons, Ltd. Substituted N‐(silatran‐1‐ylmethyl) acetamides were prepared by the reactions of triisopropanolamine with N‐methyl‐N‐(trimethoxysilylmethyl)acetamide and 2,2‐dimethoxy‐4‐acetyl‐1‐oxa‐4‐aza‐2‐silacyclohexane. The structures of the silatrane moieties are superpositions of unsymmetrical and symmetrical stereoisomers with no additional O → Si coordination between the central atom and exocyclic substituent. The silatranes are partial muscarinic agonists which demonstrate submaximal effect and mimic the effect of acetylcholine by binding directly to cholinoreceptors of the ileal smooth muscle.