Synthesis and Pharmacological Characterization of Sila-panamesine, a Sila-Analogue of the Receptor Ligand Panamesine (EMD 57445)
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- 作者：Rainer Ilg ; Christian Burschka ; Dirk Schepmann ; Bernhard Wü ; nsch ; Reinhold Tacke
- 刊名：Organometallics
- 出版年：2006
- 出版时间：October 23, 2006
- 年：2006
- 卷：25
- 期：22
- 页码：5396 - 5408
- 全文大小：338K
- 年卷期：v.25,no.22(October 23, 2006)
- ISSN：1520-6041
文摘
Sila-substitution (C/Si exchange) at the 4-position of the piperidine skeleton of the 
receptor ligandpanamesine (1a, EMD 57445) leads to sila-panamesine (1b). Compounds 1a and 1b were synthesized inmultistep syntheses, starting from 1-benzyl-4-piperidone and tetramethoxysilane, respectively, and wereisolated as the hydrochlorides 1a·HCl and 1b·HCl. ESI-MS studies of aqueous solutions of the silanol1b and the corresponding disiloxane 14 at different pH values revealed a remarkable stability of 1b. Theidentities of 1a·HCl and 1b·HCl were established by elemental analyses and multinuclear NMR studies.The 1 and 2 receptor affinities of the C/Si analogues panamesine (1a) and sila-panamesine (1b) weredetermined in competitive radioligand receptor binding studies. It was shown that the C/Si exchangeresults in a 3-fold enhancement of 1 receptor affinity.
receptor ligandpanamesine (1a, EMD 57445) leads to sila-panamesine (1b). Compounds 1a and 1b were synthesized inmultistep syntheses, starting from 1-benzyl-4-piperidone and tetramethoxysilane, respectively, and wereisolated as the hydrochlorides 1a·HCl and 1b·HCl. ESI-MS studies of aqueous solutions of the silanol1b and the corresponding disiloxane 14 at different pH values revealed a remarkable stability of 1b. Theidentities of 1a·HCl and 1b·HCl were established by elemental analyses and multinuclear NMR studies.The 1 and 2 receptor affinities of the C/Si analogues panamesine (1a) and sila-panamesine (1b) weredetermined in competitive radioligand receptor binding studies. It was shown that the C/Si exchangeresults in a 3-fold enhancement of 1 receptor affinity.