The Vespiary

The Hive => Methods Discourse => Topic started by: Cyrax on September 15, 2002, 09:58:00 AM

Title: PCP Patents, a compendium
Post by: Cyrax on September 15, 2002, 09:58:00 AM

Patent GB836083 (

Patent GB837747 (

Patent US2921076 (

Patent US3097136 (

Patent US3145229 (

Patent US5248686 (

Oderint dum metuant.  (emperor Caligula)
Title: That's good news!
Post by: Bwiti on September 17, 2002, 08:19:00 PM
Thanks! There were two there that I didn't know about...  :)

Patent GB758143 (

Patent GB838748 (

Patent GB853775 (

Patent GB861350 (

Patent US3192219 (

Patent US3097207 (


Patent GB836083 (


Patent GB837747 (


Patent US5969159 (


Patent US3097136 (

Patent US3145229 (

Patent US3097136 (

Patent US3247200 (

Patent US3522273 (

Patent US2921076 (

Love my country, fear my government.
Title: Here's Another
Post by: Bwiti on September 18, 2002, 11:25:00 AM
Aminoketones And Methods For Their Production

Patent US3254124 (

Btw, does anyone have refs that involve the use of phenyl-potassium or phenyl-sodium?

Love my country, fear my government.
Title: Needed References
Post by: Bwiti on September 27, 2002, 08:30:00 AM
If you can get a hold of any of these, please post them.

I. M. Riffin, J. Med. Soc. N. J., 57, 15 (1960)
A. J. Catenacci, D. D. Grove, W. A. Weiss, S. M. Fisher, A. M. Sismondo, and  J. H. Meyer, Antibiot. Med. Clin. Therapy, 6, 145 (1959)
M. W. Johnstone, Der. Anaesthesist, 9, 114 (1960)
G. deCastro and P. Mundeleer, Agressologie, 1, 511, (1960)
B. J. Muir, V. Evans, and J. J. Mulcahy, Brit. J. Anesthesia, 33, 51 (1961)
N. Kursanov, J. Russ. Phys. Chem. Soc., 38, 1295 (1907); Chem. Abstr., 1, 2093 (1907)
D. Lednicer and P. F. Von Voigtlander, J. Med. Chem., 22, 1157 (1979)
D. Lednicer, P. F. Von Voigtlander, and D. E. Emmert, J. Med. Chem., 23, 424 (1980)
D. C. K. Lin, A. F. Fentiman, and R. L. Foltz, Biomed. Mass Spectrom., 2, 206 (1975)
Leccese, A. P.; Marquis, K. C.; Mattia, A.; Morton, J. E. Behav. Brain Res. 1986, 19, 163
Rogawski, M. A.; Thurkauf, A.; Yamaguchi, S.; Rice, K. C.; Jacobson, A. E.; Mattson, M. V. J. Pharmacol. Exp. Ther. 1989, 249, 708-712
Geneste, P.; Herrmann, P.; Kamenka, J. M.; Pons, A. E.; Rice, K. C. J. Chem. 1988, 31, 1625
Synthesis of trans-2- (1-Aryl-1-methylethyl)cyclohexylamines
Lee, W.-y.; Salvador, J. M.; Bodige, K.;
Org. Lett.; (Communication); 2000; 2(7); 931-932.  
  Peace! 8)

Love my country, fear my government.
Title: More PCP
Post by: Rhodium on September 27, 2002, 11:02:00 AM
Here are the online articles from your list - the other ones are only available in paper edition.

4-(p-Bromophenyl)-4-(dimethylamino)-1-phenethylcyclohexanol, an Extremely Potent Representative of a New Analgesic Series
Daniel Lednicer, Philip F. VonVoigtlander

J. Med. Chem., 22, 1157 (1979) (


4-Amino-4-arylcyclohexanones and Their Derivatives, a Novel Class of Analgesics. 1. Modification of the Aryl Ring
Daniel Lednicer, Philip F. VonVoigtlander, and D. Edward Emmert

J. Med. Chem., 23, 424 (1980) (


Synthesis of trans-2-(1-Aryl-1-methylethyl)cyclohexylamines
Wen-yee Lee, James M. Salvador, Kalavathi Bodige

Org. Lett. 2(7), 931-932 (2000) (

Title: Rigid PCP Analogs - Binding to Sigma/PCP receptors
Post by: Rhodium on November 11, 2002, 02:19:00 PM
Rigid Phencyclidine Analogues. Binding to the Phencyclidine and ?1 Receptors
Robert M. Moriarty, Livia A. Enache, Lei Zhao, Richard Gilardi, Mariena V. Mattson, and Om Prakash

J. Med. Chem. 1998, 41, 468-477 (1988) (


Three phencyclidine (PCP) analogues possessing a highly rigid carbocyclic structure and an attached piperidine ring which is free to rotate were synthesized. Each analogue has a specific fixed orientation of the ammonium center of the piperidinium ring to the centrum of the phenyl ring. The binding affinities of the rigid analogues 1-piperidino-7,8-benzobicyclo[4.2.0]octene (14), 1-piperidinobenzobicyclo[2.2.1]heptene (16), and 1-piperidinobenzobicyclo[2.2.2]octene (13) for the PCP receptor ([3H]TCP) and ?-receptor (NANM) were determined. The three analogues show low to no affinity for the PCP receptor but good affinity for the ?-receptor and can be considered ?-receptor selective ligands with PCP/? ratios of 13, 293, and 368, respectively. The binding affinities for the ?-receptor are rationalized in terms of a model for the ?-pharmacophore.
Title: but these links dont give the beggining
Post by: 12345x on November 13, 2002, 04:58:00 AM
Title: PCC
Post by: Rhodium on November 13, 2002, 06:18:00 AM
Thanks, we don't need your drivel when we have this fine document written in english: (

Title: PCP byproducts
Post by: Rhodium on November 24, 2002, 05:08:00 AM
Discussion of byproducts arising from the synthesis of PCP via PCC:

Isolation, Identification, and Synthesis of Compounds Cosynthesized in the Preparation of Phencyclidine
Louis A. Jones, Rodney W. Beaver, and Terry L. Schmoeger

J. Org. Chem. 46, 3330-3333 (1981) (

Title: piperidine n' sernyl
Post by: Bwiti on November 24, 2002, 07:44:00 AM
Every time I turn around, someone feels the need to limit and cause problems for themselves by needing piperidine to synth Sernyl. Piperidine isn't needed when many other amines will do just fine. Here's a synth for benzylamine, along with a bunch more benzyl-type amines;

Patent US2608584 (


Poke around at (

and you'll find more amine synths. Peace! 8)

Love my country, fear my government.
Title: Fluorinated PCP Analogs
Post by: Rhodium on November 15, 2003, 01:20:00 PM

J. Fluorine. Chem. 114(1), 39-42 (2002) (

Title: More PCP related studies
Post by: 7is on May 14, 2004, 03:26:00 PM
The convulsant and anticonvulsant effects of phencyclidine (PCP) and PCP analogues in the rat.
Leccese AP, Marquis KL, Mattia A, Moreton JE.
Behav Brain Res. 1986 Feb;19(2):163-9

The pro- and anticonvulsant effects of phencyclidine (1-[1-phenylcyclohexyl]piperidine HCl, PCP), a number of its analogues, and SKF 10047 were investigated in rats. The PCP analogues were compounds produced by substitutions for the phenyl and piperidine rings of PCP and were selected to elucidate the structure-activity relationships existing between PCP and its pro- and/or anticonvulsant effects. All of the compounds, except ketamine, induced convulsions at high (12.8-25.6 mg/kg, i.v.), yet almost always sublethal doses. Ketamine failed to induce convulsions, even at lethal doses (51.2 mg/kg, i.v.). The acute pro- or anticonvulsant actions of PCP were then investigated. Rats were subjected to transorbital electroconvulsive shock subsequent to i.p. injections of saline or 0.625, 2.5, 5.0, 10.0 or 20.0 mg/kg PCP. It was found that PCP induced an acute, dose-dependent anticonvulsant effect. The acute pro- and/or anticonvulsant actions of the remaining compounds were then investigated by administration of electroconvulsive shock subsequent to i.p. injections of saline or one of two doses of each compound. The low and high doses of each compound were selected to be behaviorally equivalent to 2.5 and 10.0 mg/kg PCP i.p., respectively. With one exception, each dose of each drug induced an acute anticonvulsant action, with no difference in efficacy between the compounds tested. However, PCA (produced by substitution of an amine for the piperidine ring of PCP) induced a statistically greater anticonvulsant action at the higher, compared to the lower, dose. In addition, PCA was the only compound to eliminate all motor signs of the electrically induced seizure.


Synthesis, phencyclidine-like pharmacology, and antiischemic potential of meta-substituted 1-(1-phenylcyclohexyl)-1,2,3,6-tetrahydropyridines.
Thurkauf A, de Costa B, Mattson MV, France CP, Price MT, Olney JW, Woods JH, Jacobson AE, Rice KC.
J Med Chem. 1990 Aug;33(8):2211-5.

A series of 1-[1-arylcyclohexyl]-1,2,3,6-tetrahydropyridines were prepared by the reaction between 1-(1-cyanocyclohexyl)-1,2,3,6-tetrahydropyridine (1) and an appropriately substituted Grignard reagent. The resulting compounds were tested for their phencyclidine binding site affinities. Selected compounds were then tested for their ability to produce ketamine appropriate responding in monkeys and/or to show neuroprotective effects in a baby rat hypoxia/ischemia model. While it was found that binding site affinity correlated well with discriminative stimulus effects, it was found to be a poor indicator of neuroprotective efficacy within this series.


Structure-function relationships in the inhibition of synaptosomal dopamine uptake by phencyclidine and analogues: potential correlation with binding site identified with [3H]phencyclidine.
Vignon J, Lazdunski M.
Biochem Pharmacol. 1984 Feb 15;33(4):700-2.


Structure-activity relationships of phencyclidine derivatives in rat cerebellum.
Pang K, Johnson SW, Maayani S, Freedman R.
Pharmacol Biochem Behav. 1986 Jan;24(1):127-34

The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.


Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs.
Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R.
Pharmacol Biochem Behav. 1989 Mar;32(3):699-705.

Thirty-seven arylcyclohexylamines including phencyclidine (PCP) and derivatives, N[1-(2-thienyl)cyclohexyl]piperidine (TCP) and derivatives and N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) were assessed for their ability to inhibit [3H]PCP binding and [3H]dopamine ([3H]DA) synaptosomal uptake. Their pharmacological property (ataxia) was measured by means of the rotarod test. A very good correlation was observed between the inhibition of [3H]PCP binding and the [3H]DA uptake only for arylcyclohexylamines bearing an unmodified phenyl group. Conversely the comparison between the inhibition of [3H]PCP binding and the activity in the rotarod test shows a good correlation with arylcyclohexylamines having any aromatic group (phenyl, substituted phenyl and thienyl rings). This study outlined a new compound (BTCP) without ataxic effect, which is one of the more potent inhibitors of the [3H]DA uptake (IC50 = 8 nM) and which seems very specific since it has a low affinity for [3H]PCP receptors (IC50 = 6 microM). These data show that the aromatic group of the compounds leads to molecules that bind differently to the PCP receptor and to the DA uptake complex. They also suggest that the behavioral properties of arylcyclohexylamines revealed by the rotarod test occur essentially as a result of an interaction with the sites labeled with [3H]PCP and that TCP is more selective than PCP itself in this recognition.


Phencyclidine-like effects of tetrahydroisoquinolines and related compounds.
Gray NM, Cheng BK, Mick SJ, Lair CM, Contreras PC.
J Med Chem. 1989 Jun;32(6):1242-8.

A series of 1,2,3,4-tetrahydroisoquinolines, tetrahydrothieno[2,3-c]pyridines, and related compounds were evaluated for their ability to inhibit binding of [3H]-1-[1-(2-thienyl)piperidine and [3H]-N-allylnormetazocine to phencyclidine (PCP) and sigma receptors, respectively. A representative series of compounds was evaluated in behavioral assays to determine the ability of the compounds to induce PCP-like stereotyped behavior and ataxia. All of the compounds caused stereotyped behavior and ataxia, indicating their agonist actions at the PCP site.


Pharmacokinetic and pharmacodynamic properties of some phencyclidine analogs in rats.
Cho AK, Hiramatsu M, Schmitz DA, Nabeshima T, Kameyama T.
Pharmacol Biochem Behav. 1991 Aug;39(4):947-53.

The pharmacodynamics and pharmacokinetics of three phencyclidine analogs, differing from phencyclidine (PCP) only in the nature of the amine structure, were determined after intravenous doses of equimolar amounts to rats. The purpose of the study was to assess the role of pharmacokinetics in the in vivo potency of the compounds. The compounds examined were phenylcyclohexyl-pyrrolidine (PCPY), diethylamine (PCDE), ethylamine (PCE), and phencyclohexylamine (PCA). The behavior responses monitored included ataxia and others previously shown to be characteristic of PCP. In contrast to their relative affinities for the MK 801 binding site, the behavioral potencies of PCE, PCDE and PCPY were comparable to PCP. The major discrepancy occurred with PCDE, whose affinity for the NMDA receptor was 1/20th of PCP. The pharmacokinetic studies showed that the discrepancy between in vivo and in vitro activity of PCDE could be partially accounted for by its conversion to PCE, a relatively potent PCP-like agent.


PCP: a review of synthetic methods for forensic clandestine investigation.
Allen AC, Robles J, Dovenski W, Calderon S.
Forensic Sci Int. 1993 Oct;61(2-3):85-100.

A review of the synthetic routes to phencyclidine (PCP, 1-(1-phenylcyclohexyl)piperidine) available in the open literature is presented. The emphasis herein is directed toward the forensic investigation of clandestine PCP laboratories. Six published synthetic routes to PCP/analogs are discussed. Each method is rated for overall yield, degree of difficulty and potential hazard, in order to assist the forensic chemist in evaluation of a particular clandestine operation. One clandestine recipe is illustrated and discussed.


N-methyl-D-aspartate antagonists and drug discrimination.
Koek W.
Pharmacol Biochem Behav. 1999 Oct;64(2):275-81.

Excitatory amino acids (EAA), such as glutamate, are thought to be involved in various disorders (e.g., ischemic brain damage, epilepsy, Parkinson's disease), and EAA antagonists have been suggested as potential treatments for these disorders. Phencyclidine (PCP), with produces psychotomimetic effects in humans, has antagonist properties at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors that have been suggested to underlie some of its actions. This suggestion, and concern about possible psychotomimetic activity, has stimulated research aimed at examining to what extent the behavioral profile of other NMDA antagonists resembles that of PCP. Drug discrimination (DD) is prominent among the procedures used to carry out such comparisons. The results of clinical studies with NMDA antagonists provide feedback about the predictive validity of the DD procedures used to characterize their preclinical behavioral profile. Further, DD is used also to examine the ability of compounds to attenuate the discriminative stimulus (DS) effects of PCP-type drugs, and results of such studies have been suggested to provide evidence of antipsychotic potential. Finally, although many instances of intermediate responding in DD can be explained by low efficacy at the receptors that mediate the DS effects of the training drug, certain outcomes produced by PCP-type drugs do not offer valid measures of efficacy, and require more detailed behavioral analyzes.


Effect of lowered lipophilicity on the affinity of PCP analogues for the PCP receptor and the dopamine transporter.
Hamon J, Vignon J, Kamenka JM
Eur J Med Chem (1996) 31, 489-495

Oxygen and sulphur atoms were introduced in the cyclohexyl and piperidinyl moieties of the basic structures 1-(1-phenyl-cyclohexyl)piperidine (PCP), 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), and 1-[1-(2-benzothiophenyl)cyclohexyl]piperidine (BTCP) to lower their global lipophilicity. The compounds obtained were tested comparatively for their affinity for the PCP receptor labelled with [3H]TCP and for the dopamine (DA) transporter labelled with [3H]BTCP. Lowering the global lipophilicity in PCP and TCP series is detrimental to the affinity and selectivity for the PCP receptor. In the BTCP series lowering of the global lipophilicity is less deleterious and may, on the contrary, be a useful way of increasing selectivity for the DA transporter in some instances.


Discriminative stimulus properties of phencyclidine (PCP)-related compounds: correlations with 3H-PCP binding potency measured autoradiographically.

Kozlowski MR, Browne RG, Vinick FJ.
Pharmacol Biochem Behav. 1986 Nov;25(5):1051-8.

Several PCP analogs, the putative PCP agonist MDP, and the sigma receptor agonists SKF-10,047 and dexoxadrol were tested for their ability to substitute for PCP in animals trained to discriminate PCP from saline. The potencies of these compounds in substituting for PCP in the behavioral task correlated with their abilities to inhibit the specific binding of 3H-PCP to rat hippocampal sections measured autoradiographically, which occurred at a single class of sites with an affinity of 85 nM and a capacity of 2646 fmol/mg protein. In addition to this specific binding, an additional nonspecific but displaceable fraction of total 3H-PCP binding was present. These results suggest that the specific 3H-PCP binding site measured in the hippocampus may be the type of binding site which mediates the behavioral effects of PCP and related compounds. Therefore, measurement of the inhibition of 3H-PCP binding at this site might aid in the search for PCP antagonists.


Title: Even more PCP studies
Post by: 7is on May 14, 2004, 04:03:00 PM
Discriminative stimulus effects of N-substituted analogs of phencyclidine in rhesus monkeys.
Solomon RE, Herling S, Domino EF, Woods JH.
Neuropharmacology. 1982 Dec;21(12):1329-36.

In daily sessions of a two-lever, discrete-trial, food-reinforced procedure, rhesus monkeys were trained to discriminate between subcutaneous injections of ketamine (1.0 or 1.8 mg/kg) and control injections. In tests of stimulus generalization, cumulative doses of drugs were administered in single sessions and either control- or ketamine-appropriate responding produced food. Ketamine (1.8 and 3.2 mg/kg) and phencyclidine (0.32 mg/kg) produced an average of more than 90% ketamine-appropriate responding. In contrast, d-amphetamine, atropine, chlorpromazine, codeine, diazepam and quipazine, tested at doses up to and including those that markedly reduced response rates, produced exclusively control-appropriate responding. Dose-related ketamine-appropriate responding was produced by each of ten 1-phenylcyclohexylamines, the potencies of which varied with the length, electronegativity, and number of N-alkyl chains present. The most potent analog of phencyclidine, N-ethyl-1-phenylcyclohexylamine, was approximately equipotent with phencyclidine. These data are consistent with previous reports that the discriminative stimulus effects produced by phencyclidine are representative of a unique class of drugs, and that alkyl substitutions in the region of the piperidine ring alter the potency, but not the characteristic pharmacological activity, of the resulting analogs. The potencies of some of these analogs compared to phencyclidine in rhesus monkeys, however, differed from their relative potencies in rodents. Thus, there appear to be species differences in the role of the nitrogen pharmacophore of these compounds in producing phencyclidine-like behavioral effects.


Discriminative stimulus effects of monohydroxylated phencyclidine metabolites in Rhesus monkeys.
Solomon RE, Herling S, Woods JH.
Eur J Pharmacol. 1982 Aug 27;82(3-4):233-7.

Rhesus monkeys were trained to discriminate saline from an injection of ketamine. In tests of stimulus generalization, phencyclidine (PCP) produced dose-related ketamine-appropriate responding in each monkey. Two monohydroxylated PCP metabolites also produced ketamine-like discriminative effects, although only at considerably higher doses than did PCP. A third monohydroxylated PCP metabolite produced only sham-appropriate responding. The results suggest that these PCP metabolites contribute little to the behavioral actions of PCP in the monkey.


Biochemical properties of the brain phencyclidine receptor.
Vignon J, Vincent JP, Bidard JN, Kamenka JM, Geneste P, Monier S, Lazdunski M.
Eur J Pharmacol. 1982 Jul 30;81(4):531-42.

This paper gives a detailed account of techniques which can be used to measure [3H]phencyclidine binding to its receptor. The main properties of the binding component are the following: (i) It is rapidly heat-inactivated at temperatures over 50 degrees C. (ii) It is destroyed by proteases like trypsin, pronase or papain suggesting that it is of a protein nature. The receptor structure is resistant to chymotrypsin. (iii) A good correlation was found between the pharmacological activity of 30 different analogs as measured by the rotarod assay and the affinity of these different molecules for the phencyclidine receptor. (iv) Monovalent and divalent cations antagonize [3H]phencyclidine binding to its receptor. The dissociation constant is 15 mM, the same for Na+, Li+, K+, cholinium or Tris. Na+ (and other monovalent cations) and phencyclidines bind to distinct sites. The saturation of the Na+ site by Na+ modulates the affinity of phencyclidine for its receptor. Divalent cations antagonize [3H]phencyclidine binding in the absence of Na+. This antagonism is of the non-competitive type. (v) [3H]phencyclidine binding is also antagonized by histrionicotoxin and by local anaesthetics.


18F-PCP analogs for positron emission tomography (PET)
 Van Dort, M. E., D. J. Yang, M. R. Kilbourn, D. J. Gole, A. Kalir, D. C. Chu, A. B. Young, E. F. Domino and D. M. Wieland.
Pharmacology Biochemistry and Behavior, Volume 28, Issue 1, September 1987, Pages 142-143


There are some interesting studies in rhodium´s site, some of them didn´t seem to be referenced here at the hive. Or am I missing something? (

Can anyone post that one?

Structure-activity relationship studies of phencyclidine derivatives in rats.
Cone EJ, McQuinn RL, Shannon HE.
J Pharmacol Exp Ther. 1984 Jan;228(1):147-53

Phencyclidine (PCP), a semirigid molecule containing a cyclohexane ring with vicinally attached aromatic and piperidine rings, produces characteristic discriminative stimulus properties and pupillary miosis in rats. The effectiveness of a series of aromatic and nitrogen substituted analogs of PCP in producing PCP-like discriminative stimuli and changes in pupil diameter was determined in rats trained to discriminate between saline and 3.0 mg/kg of PCP. Dexoxadrol and its optical isomer levoxadrol were also evaluated for purposes of comparison. Analogs in which the electron-density of the aromatic ring was increased (3NH2-PCP) or only slightly reduced (3F-PCP) retained PCP-like activity. A loss of PCP-like activity occurred with analogs in which the electron-density of the aromatic ring was greatly reduced (3NO2-PCP) or extended to a larger system (1NCP and 2NCP). PCP-like activity also was abolished in analogs in which the distance between the aromatic ring and the remainder of the molecule was systematically increased by one, two or three methylene units. In contrast, substitutions on the nitrogen atom altered the potency, but not the efficacy, of such analogs. Dexoxadrol produced PCP-like activity whereas its optical enantiomer levoxadrol was devoid of such activity. These findings suggest a drug receptor surface with multiple domains or subsites which recognize regions of structural overlap among the phencyclidines, dioxolanes and psychotomimetic benzomorphan derivatives.

BTW, does anyone know any good books about NMDA antagonists, or just good book chapters?
Title: Just one missing
Post by: Nicodem on May 15, 2004, 01:09:00 AM
7is, you did a great job. What a collection!

Can anyone post that one? ... J Pharmacol Exp Ther. 1984 Jan;228(1):147-53

And who ever will go to the library would make me a favor if he would also scann this other PCP related paper from JPET as well :)

Sigma compounds derived from phencyclidine: identification of PRE-084, a new, selective sigma ligand
TP Su, XZ Wu, EJ Cone, K Shukla, TM Gund, AL Dodge and DW Parish
J. Pharmacol. Exp. Ther. 259(2), (1991) 543-550.

A series of compounds derived from phencyclidine (PCP) was examined in the sigma receptor and PCP receptor binding assays. The derivatives included compounds containing methylene, ethylene or carboxyl ethylene insertion between the cycloalkyl ring and the amine group of PCP. Various phenyl substitutions, cycloalkyl rings and amines of these derivatives were also examined. The methylene and ethylene insertions decreased the compounds' potencies at PCP receptors, whereas they increased the potencies at sigma receptors. The carboxyl ethylene insertion produced compounds with negligible potencies at PCP receptors while possessing high potencies for sigma receptors. One derivative (PRE-084; 2-(4-morpholino)ethyl 1-phenylcyclohexane-1-carboxylate hydrochloride) had an IC50 of 44 nM in the sigma receptor assay, an IC50 of more than 100,000 nM for PCP receptors and an IC50 higher than 10,000 nM in a variety of other receptor systems. In general, compounds with hydroxy-substituted phenyl groups tended to have decreased potency at sigma receptors, whereas methylphenyl and chlorophenyl substitutions increased potencies. Reduction of cycloalkyl ring size decreased potencies for sigma receptors and quaternized amine groups invariably lowered the compound's potencies. Conformational analysis indicated that PRE-084 fitted onto a pharmacophore model for the sigma ligands. The study describes a new, highly selective ligand for the sigma receptor. The results of this study also confirm distinctly different structural requirements for binding to sigma and PCP receptors and provide a new structural consideration for synthesizing sigma-selective compounds.

Title: Wonderful Stuff
Post by: Aurelius on May 17, 2004, 08:29:00 PM
Those links should all be put into the PCP Pharm Digest.  (and a select few into the synth digest)

Title: Kalir - PCP analog SAR book chapter
Post by: 7is on June 17, 2004, 06:53:00 AM
Structure Activity Relationships of Phencyclidine Derivatives
Asher Kalir
PCP (phencyclidine), historical and current perspectives /editor, Edward F. Domino. Ann Arbor : NPP Books, c1981. p. 31-47


Title: The Synthesis of Phencyclidine and Other ...
Post by: thallium on July 29, 2004, 08:16:00 AM
The Synthesis of Phencyclidine and Other 1-Arylcyclohexylamines
Maddox, VH.; Godefroi, EF.; Parcell, RF.
J. Med. Chem. 1965 (8) 230-235


Various 1-arylcyclohexylamines were synthesized for evaluation as central nervous system depressants.
The compounds were prepared by several procedures. 1-(1-Phenylcyclohexyl)piperidine, the first compound of this type synthesized, was prepared from 1-piperidinocyclohexanecarbonitrile by replacement of the cyano group by phenyl using phenylmagnesium bromide. These compounds were tested for cataleptoid activity and antitonic extensor properties.