Synthesis and anticonvulsant activity of 1-phenylcyclohexylamine analogs

Abstract

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 [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine. Many of the analogues were protective against MES seizures (ED50s of 5-41 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.

Preparation and analytical characterization of 1‐(1‐phenylcyclohexyl)piperidine (PCP) and 1‐(1‐phenylcyclohexyl)pyrrolidine (PCPy) analogues

“…197-197.7 C (lit value: 195-196 C [17] ). The solvent was then evaporated under a stream of warm air and the resulting oil dissolved in acetone (10 ml).…”

New designer drug N‐(1‐phenylcyclohexyl)‐3‐ethoxypropanamine (PCEPA): Studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques

“…2(B), VII). In case of the 4 0 -hydroxy metabolites (4,5,11,12),ˇ-cleavage between positions 1 0 and 2 0 or between 1 0 and 6 0 and the above-mentioned rearrangement were followed by homolytic cleavages between positions 4 0 and 5 0 or between 3 0 and 4 0 , respectively ( Fig. 2(C), III).…”

Remarkable amine-TFA self assembly

“…Cis and trans -4-tert-butyl-1-phenylcyclohexylamine (1-cis and 1-trans) were synthesized using known procedures [32,33] and characterized by 1 H NMR. NOE was used to confirm which is the trans isomer, on the basis of the interaction between the phenyl hydrogen atoms and the hydrogen atoms at positions 3 and 5 of the cyclohexyl ring.…”