Sila-biperiden undendo-Sila-biperiden: Synthesen, Kristallstrukturen und antimuscarinische Eigenschaften

摘要: Summary Starting from trichloro(vinyl)silane (Cl 3 SiCH=CH 2 ), the muscarinic antagonists sila- biperiden [ rac -(Si RS ,C2 SR ) -exo - ] and endo -sila-biperiden )- were prepared by a seven-step synthesis. Both silanols are configurationally stable in inert organic solvents but undergo slow epimerization aqueous solution (pH 7.4, 32°C) inversion of configuration at silicon atom. The relative configurations sila-biperiden -sila- determined single-crystal X-ray diffraction. compounds form intermolecular O-H ⋯ N hydrogen bonds crystal leading to formation centrosymmetric dimers (sila-biperiden) infinite chains ( -sila-biperiden), respectively. Sila-biperiden is analogue (C/Si exchange) antiparkinsonian drug -(C /C2 1 ]. In functional pharmacological experiments, as well radioligand competition studies, biperiden, behaved simple competitive M1-, M2-, M3- M4-receptors. three displayed highest affinity for M1-receptors (pA values: 8.72–8.80; pK i 8.8–9.1), intermediate M4- M3-receptors, lowest M2-receptors 7.57–7.79; 7.7–7.8). profile (M1 ≫ M4 M3 M2) qualitatively similar that M1-selective antagonist pirenzepine. antimuscarinic properties C/Si analogues almost identical.