7583-85-9Relevant academic research and scientific papers
Synthesis, in Vitro Acetylcholine-Storage-Blocking Activities, and Biological Properties of Derivatives and Analogues of trans-2-(4-Phenylpiperidino)cyclohexanol (Vesamicol)
Rogers, Gary A.,Parsons, Stanley M.,Anderson, D. C.,Nilsson, Lena M.,Bahr, Ben A.,et al.
, p. 1217 - 1230 (1989)
Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ.The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol.The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography.The absolute configuration of (-)-vesamicol is 1R,2R.Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue.Alterations to all three rings can have large effects on potency.Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency.A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications.A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.
