100274-02-0Relevant articles and documents
Preparation and Properties of the Enantiomers of the Selective Antimuscarinic Agent 1-Cyclohexyl-1-phenyl-4-piperidino-1-butanol (Hexahydro-Difenidol)
Tacke, Reinhold,Strohmann, Carsten,Sarge, Stefan,Cammenga, Heiko K.,Schomburg, Dietmar,et al.
, p. 137 - 144 (2007/10/02)
Using (S)- or (R)-mandelic acid as the resolving agent, the enantiomers of 1-cyclohexyl-1-phenyl-4-piperidino-2-butin-1-ol were prepared (enantiomeric purity: ee = 99.7percent; calorimetric analysis).Catalytic hydrogenation (Pd/C contact) of (R)-2 and (S)-2 yielded the enantiomers of 1-cyclohexyl-1-phenyl-4-piperidino-1-butanol which were isolated as hydrochlorides .The absolute configuration of the enantiomers of 1a and 2 was determined by an X-rey crystal structure analysis of the mandelate (S)-1a*(R)-C6H5CH(OH)COOH. (R)-Hexahydro-difenidol and (R)-2 exibit a higher affinity for the atrial M2α and ileal M2β muscarinic receptors of the guinea pig than the respective antipodes (S)-1a and (S)-2 (atrial stereoselectivity index: 17 and 8.6, respectively; ileal stereoselectivity index: 193 and 44, respectively).In addition, (R)-1a and (R)-2 exhibit a significantly higher affinity for the M2β receptors of the ileum than for the M2α receptors of the atrium (atrium/ileum ratio: 21 and 10, respectively).Thus, (R)-1a and (R)-2 are valuable tools for the identification and characterization of muscarinic M2 subtypes.In contrast, the less potent (S)-enantiomers of 1a and 2 do not differentiate between M2α and M2β receptors.
