Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brown oxidation of cis-bicyclo[3.1.0]hexan-3-ol afforded bicyclo[3.1.0]hexan-3-one in 98% yield. Treatment of this ketone with either phenyllithium or phenylamagnesium bromide in ether at room temperature followed by solvolysis of the resulting alcohol in a mixture of trifluoroacetic acid, sodium azide, and chloroform gave a mixture of cis- and trans-3-azido-3-phenylbicyclo[3.1.0]hexanes. LAH reduction of this crude mixture of azides afforded a 1:3.5 mixture of cis- and trans-3-phenyl-3-bicyclo[3.1.0]hexylamine, respectively, in 51% overall yield from the alcohol. Separation of the mixture of amines by column chromatography followed by cyclization of each by heating at 60 degrees C in DMF solution with 1 equiv of 1,5-dibromopentane furnished the two conformationally restrained analogues of phencyclidine (PCP), cis- and trans-3-phenyl-3-piperidinylbicyclo[3.1.0]hexane (1 and 2, respectively), in high yield. Configurations were assigned on the basis of an X-ray crystallographic analysis of the cis isomer (1). Bond lengths and angles are similar to those found in PCP and its derivatives. Binding to PCP receptors and sigma sites as well as behavioral effects of 1 and 2 in rats was determined relative to PCP. In displacement of specifically bound [3H]TCP (1-[1-(2-thienyl)cyclohexyl]piperidine) from PCP receptors, 1 and 2 were nearly equipotent and about one-seventh as potent as PCP. These compounds were about one-fifth as potent as PCP in displacing [3H]-(+)-SKF 10,047 from its binding site. Calculation of the ED50 values of 1 and 2 for stereotyped behavior and ataxia indicated that they were about equipotent, and 2-3-fold less active than PCP.
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PMID:Synthesis, configuration, and evaluation of two conformationally restrained analogues of phencyclidine. 339 94

Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP) has shown analgesic effects. Some of its derivatives were synthesized and their biological properties were studied. To date, only saturated ketones have been used as starting materials for synthesizing the phencyclidine family. In order to show desirable biological activity, the aromatic and piperidine rings are necessary for these compounds. Using alpha-tetralone as a starting material, 2-hydroxy-1-(-phenyltetralyl)piperidine, an analogue of the phencyclidine family, and some of its intermediates were synthesized. This ketone was reacted with phenyl magnesium bromide and the resultant alcohol was reacted with acetic anhydride to give alkene that was treated with potassium permanganate to give diol. This compound was treated with a suspension of sodium azide and trichloroacetic acid to give the azide compound that was reduced with LiAlH4 to give the primary amine. Cyclization of this compound with 1,5-dibromopentane finally gave a tertiary amine. It is predicted that the title compound 2-hydroxy-1-(1-phenyltetralyl)piperidine exerts a potent analgesic effect on acute and phasic pain.
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PMID:Synthesis and biological properties of 2-hydroxy-1-(1-phenyltetralyl)piperidine and some of its intermediates as derivatives of phencyclidine. 1622 17