2201-17-4Relevant academic research and scientific papers
Synthesis and Anticonvulsant Activity of 1-Phenylcyclohexylamine Analogues
Thurkauf, Andrew,Costa, Brian de,Yamaguchi, Shun-ichi,Mattson, Mariena V.,Jacobson, Arthur E.,et al.
, p. 1452 - 1458 (2007/10/02)
Thirty-eight analogues of 1-phenylcyclohexylamine (PCA), a phencyclidine (PCP) derivative, were examined for their activities in the mouse maximal electroshock (MES) seizure test and in a motor-toxicity assay.In addition, we determined the binding affinities of the compounds for PCP acceptor sites in rat brain membranes labeled with -1-piperidine.Many of the analogues were protective against MES seizures (ED50s of 4-41 mg/kg, ip) and all of these compounds caused motor toxicity.The potencies in the motor toxicity and MES seizure tests showed a moderate correlation with the affinities for PCP sites.Several analogues exhibited a greater separation of potencies in the motor toxicity and MES seizure tests than did the parent compound PCA.These were obtained by (i) 3-methylation of the cyclohexyl ring trans to the phenyl ring, (ii) methoxylation at the ortho position on the phenyl ring, and (iii) contraction of the cyclohexane ring to form the corresponding cyclopentane.
4-Amino-4-arylcyclohexanones and Their Derivatives, a Novel Class of Analgesics. 1. Modification of the Aryl Ring
Lednicer, Daniel,VonVoigtlander, Philip F.,Emmert, D. Edward
, p. 424 - 430 (2007/10/02)
Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues.Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated.Synthesis starts by double Michael reaction of acrylate on arylacetonitriles.Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3.Isocyanates were then converted to the title compounds.Analgesic activity is very sensitive to the nature and position of the substituent on the aromatic ring.The most potent compounds in this series (p-CH3, p-Br) showed 50percent the potency of morphine.Deletion of the ring oxygen abolishes activity.
