- Synthesis and antinociception properties of phencyclidine derivatives with modified aromatic or cycloalkyl rings and amino group
-
Phencyclidine is an arylcyclohexylamine compound which has received a lot of investigative attention due to the complex spectrum of behaviours and its complicated interactions with the central nervous system. Phencyclidine administration may act as stimulant, depressant, hallucinogen, and analgesic depending on dose and tested species. In this study, new phenyl and thienyl analogues with specific affinity for the phencyclidine sites in NMDA receptors, dopamine uptake blocking, or both of them were synthesized. The acute and chronic pain properties of these compounds were studied using the tail immersion and formalin tests on mice and the results were compared with control and phencyclidine groups at a dose of 10 mg/kg. The outcomes indicated that all synthesized compounds showed better activities to decrease acute thermal and chemical, but not chronic pains. Also, these effects were more significant for phenyl (group 1) compared to thiophene (group 2) analogues, which is probably due to the higher affinity of group 1 for inhibition of dopamine reuptake compared to binding to the phencyclidine sites in NMDA receptors in this family.
- Ahmadi, Abbas,Khalili, Mohsen,Barzin, Mahnaz,Pooladi, Mohsen,Bakhtiari, Fatemeh,Barjeste, Maede,Nahri-Niknafs, Babak
-
-
Read Online
- New morpholine analogues of phencyclidine: Chemical synthesis and pain perception in rats
-
Phencyclidine (PCP, I) and most its derivatives have demonstrated some pharmacological effects. Accordingly, in this study, the new methoxy (III) and hydroxy-methyl (IV) morpholine PCP derivatives were synthesized. The acute and chronic pain activities of these drugs (III, IV) were investigated by tail immersion and formalin tests on rats and the results were compared with those in PCP, PCM (PCP-morpholine, II), and methyl-PCM (V). Findings indicated that III (6 mg/kg, i.p.) generates more analgesic effects in tail immersion test in comparison with I and II in 20, 40, 45 and 55 min post-injection. These effects were observed in 10, 20, 40, 45 and 50 min after the application of IV (at the same dosage). This analgesic effect was markedly seen in 20, 40, 45 and 50 min after compound IVs application in comparison with the drugs (I-V). In formalin test analysis, the acute chemical pain (Phase I) could not be affected by any drugs (I-V) while chronic formalin pain would be diminished by these new synthesized drugs (III and IV), especially in late Phase II, compared to I and II at the dosage of 6 mg/kg. It is, therefore, concluded that these new synthesized PCP derivates including methoxy-PCM (III) and hydroxy-methyl-PCM (IV) could substantially and respectively diminish acute thermal and chronic chemical pains.
- Ahmadi, Abbas,Khalili, Mohsen,Hajikhani, Ramin,Naserbakht, Moslem
-
-
Read Online
- New amine and aromatic substituted analogues of phencyclidine: Synthesis and determination of acute and chronic pain activities
-
Background: Phencyclidine (PCP, I) is a synthetic drug with remarkable physiological properties. PCP and its analogues exert many pharmacological activities and interact with some neurotransmitter systems in the central nervous system like particular affinity for PCP sites in NMDA receptors or dopamine uptake blocking or even both. Aim and Objective: The following research, methyl group with electron-donating and dipole moment characters was added in different positions of phenyl ring along with the substitution of benzylamine (with many pharmacological effects) instead of piperidine ring of I to produce new compounds (II-V) of this family with more analgesic activities. Materials and Methods: Analgesic activities of these new compounds were measured by tail immersion and formalin tests for acute and chronic pains, respectively. Also, the outcomes were compared with control and PCP (10 mg/kg) groups. Results: The results indicate that compounds III, IV, and V have more acute and chronic antinociceptive effects than PCP and compound II which may be concerned with more antagonizing activities of these new painkillers for the blockage of dopamine reuptake as well as high affinity for NMDA receptors PCP binding site. Conclusion: It can be concluded that the benzylamine derivative of phencyclidine with a methyl group on the benzyl position on phenyl ring (V) is a more appropriate candidate to reduce acute and chronic (thermal and chemical) pains compared to other substituted phenyl analogs (II-IV) and PCP.
- Shokrollahi, Maryam,Samadizadeh, Marjaneh,Khalili, Mohsen,Sobhanian, Seyed A.,Ahmadi, Abbas
-
p. 570 - 576
(2020/01/08)
-
- Transamination of a-amino nitriles
-
α-Amino nitriles containing a primary amino group undergo transamination with aliphatic and aromatic amines under mild conditions with high yields. A probable reaction mechanism involving intermediate elimination of cyanide ion has been proposed.
- Popov,Mokhov,Tankabekyan
-
-
- Synthesis and antinociceptive behaviors of new methyl and hydroxyl derivatives of phencyclidine
-
Phencyclidine (I) and its derivatives show such pharmacological behaviors as analgesic, anticonsulvant, anti-anxiety and antidepressant, while interacting with central nervous system. In this study, new methyl and hydroxyl derivatives of PCP were synthesized and their antinociceptive behaviors in animals were examined by measuring the number of writhing in a writhing test of visceral pain and the pain scores in Formalin test. Compared to control and PCP groups, findings in experimental groups indicated the new synthesized analogues (compounds II, III and V, 10 mg/kg) of PCP were able to produce more analgesic effects in formalin and writhing tests, especially for compound V. It was concluded that the new synthesized derivatives of PCP could substantially and respectively diminish acute and chronic pains.
- Ahmadi,Kermani,Naderi,Hajikhani,Rezaee,Javadi,Niknafs
-
scheme or table
p. 763 - 769
(2012/06/30)
-
- Discovery of a novel series of selective HCN1 blockers
-
The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1. Optimization of this hit led to the identification of the potent, 1,1-disubstituted cyclohexane HCN1 blocker, 2-ethoxy-N-((1-(4- isopropylpiperazin-1-yl)cyclohexyl)methyl)benzamide. The work leading to the discovery of this compound is described herein.
- McClure, Kelly J.,Maher, Michael,Wu, Nancy,Chaplan, Sandra R.,Eckert III, William A.,Lee, Dong H.,Wickenden, Alan D.,Hermann, Michelle,Allison, Brett,Hawryluk, Natalie,Breitenbucher, J. Guy,Grice, Cheryl A.
-
scheme or table
p. 5197 - 5201
(2011/10/02)
-
- Heterogeneously catalysed Strecker-type reactions using supported Co(ii) catalysts: Microwave vs. conventional heating
-
A range of α-aminonitriles could be efficiently prepared from various aldehydes/ketones and primary or secondary amines using a highly active and stable Co(ii) complex supported on different mesoporous supports at both room temperature and low temperature microwave irradiation under solventless conditions. Catalysts were also highly reusable under the investigated reaction conditions and could be reused at least 10 times without loss of catalytic activity. The Royal Society of Chemistry.
- Rajabi, Fatemeh,Nourian, Saghar,Ghiassian, Sara,Balu, Alina M.,Saidi, Mohammad Reza,Serrano-Ruiz, Juan Carlos,Luque, Rafael
-
supporting information; experimental part
p. 3282 - 3289
(2011/12/15)
-
- Synthesis and analgesic effects of methoxy-pyrrole derivative of phencyclidine on mice
-
Phencyclidine, 1-[1-phenylcyclohexyl]piperidine (PCP, I) and its derivatives have shown considerable pharmacological effects. In this work, pyrrole derivative of phencyclidine (PCP-pyrrole, 1-[1-phenylcyclohexyl]pyrrole, II) and a new derivative (1-[1-[3- methoxyphenylcyclohexyl]pyrrole, III) and their intermediates were synthesized, then the acute and chronic pains were examined on mices at 1 mg/kg dosage using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute chemical and chronic pain) tests and the results were compared with phencyclidine and control (DMSO) groups. The results indicated that III produced more analgesic effects compared to II in tail immersion test and also revealed that the newly synthesized derivative (III) significantly reduced chronic pain (especially in initial of phase II) in formalin test compared to other groups.
- Ahmadi, Abbas,Solati, Jalal,Hajikhani, Ramin,Pakzad, Sara
-
scheme or table
p. 5429 - 5432
(2012/07/27)
-
- Efficient Co(ii) heterogeneously catalysed synthesis of α-aminonitriles at room temperature via Strecker-type reactions
-
An environmentally friendly and highly active mesoporous Co(ii) complex on mesoporous SBA-15 material could be used as an easily recoverable catalyst for the synthesis of α-aminonitriles from a wide range of aldehydes/ketones and primary or secondary amines with good to excellent conversions yields at room temperature under solventless conditions. The catalyst can be recovered by simple filtration and could be reused at least 10 times without loss of catalytic activity.
- Rajabi, Fatemeh,Ghiassian, Sara,Saidi, Mohammad Reza
-
supporting information; experimental part
p. 1349 - 1352
(2010/09/15)
-
- Synthesis and determination of acute and chronic pain activities of 1-[1-(3-methylphenyl)(tetralyl)]piperidine as a new derivative of phencyclidine via tail immersion and formalin tests
-
Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP, I) and ketamine (2-O-chlorophenyl-2-methylaminocyclohexan, CAS 1867-66-9, II) revealed some analgesic effects. Some of their derivatives have been synthesized for biological properties studies. Utilizing 1-tetralone as a starting material, 1-[1-(3-methylphenyl)(tetralyl)]piperidine, (PCP-CH3-tetralyl, III) was synthesized and its analgesic effects were studied on rats via tail immersion (as a model of acute thermal pain) and formalin (as a model of acute chemical and chronic pain) tests and compared with those of ketamine and PCP. The results indicated a marked anti-nociception 2-25 min after ketamine injection, but this analgesic effect lasted for 40 min following PCP-CH 3-tetralyl application in the tail immersion test. However, the data obtained from the formalin test showed that chronic pain could be significantly attenuated by ketamine, PCP and PCP-CH3-tetralyl. ECV·Editio Cantor Verlag, Aulendorf (Germany).
- Ahmadi, Abbas,Khalili, Mohsen,Mihandoust, Farnaz,Barghi, Leila
-
scheme or table
p. 30 - 35
(2010/04/24)
-
- Synthesis and preliminary biochemical evaluation of novel derivatives of PCP
-
(±)-Trans-Ph/Et and (±)-cis-Ph/Et 1-(2-ethyl-1- phenylcyclohexyl)piperidine were synthesized from 2-ethylcyclohexanone. In contrast to the corresponding trans-substituted 2-methyl compound which is 5x more potent than PCP, the trans-2-ethyl derivative has a 75x lower affinity for the PCP binding site. The cis-2-ethyl isomer is inactive like the cis-2-methyl derivative. (±)-1-(1-Phenylcyclohexyl)-2-methylpiperidine is almost as active as the parent PCP. Reduction of the aromatic ring or quaternization of the piperidine in PCP reduces the affinity for the PCP site.
- Linders, Joannes T. M.,Furlano, David C.,Mattson, Mariena V.,Jacobson, Arthur E.,Rice, Kenner C.
-
scheme or table
p. 79 - 87
(2011/01/13)
-
- Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3- piperidinol as a new derivative of phencyclidine in mice
-
Phencyclidine (1-(1-phenylcyclohexyl) piperidine, CAS 956-90-1, PCP, I) and its derivatives have shownmany analgesic effects. In this research, a newderivative of PCP (1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol, PD, II) was synthesized and its analgesic (acute and chronic pains) effects were examined on rats using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute and chronic chemical pain) tests and the results are compared to PCP and control groups. The results indicated that II produces higher analgesic effects in the tail immersion test compared to the PCP and control groups, with a marked and significant increase in tail immersion latency for the doses 1, 5 and 10 mg/kg. The formalin test showed that PD (II) is not effective in acute chemical pain (phase I, 0-5 min after injection) in all doses but chronic pain (initial-phase II, 15-40 min after injection) is significantly attenuated by this compound compared to PCP and saline (control) in dosesof 5 and 10 mg/kg. It is concluded that II is effective in acute thermal (in all doses) and chronic (doses of 5 and 10 mg/kg) pains; however, it is not effective in acute chemical pain compared to PCP and control. ECV · Editio Cantor Verlag.
- Ahmadi, Abbas,Solati, Jalal,Hajikhani, Ramin,Onagh, Masoud,Javadi, Mojdeh
-
scheme or table
p. 492 - 496
(2011/05/09)
-
- Synthesis and study on analgesic effects of 1-[1-(4-methylphenyl) (cyclohexyl)] 4-piperidinol and 1-[1-(4-methoxyphenyl) (cyclohexyl)] 4-piperidinol as two new phencyclidine derivatives
-
Phencyclidine (1-(1-phenylcyclohexyl) piperidine; CAS 956-90-1; PCP, I) has shown analgesic effects. Some of its derivatives have been synthesized and their biological properties have been studied. In this work, new methyl and methoxy hydroxyl derivatives of phencyclidine were synthesized and the analgesic effects of this compounds [(1-[1-(4-methylphenyl) (cyclohexyl)] 4-piperidinol, II), (1-[1-(4-methoxyphenyl) (cyclohexyl)] 4-piperidinol, III)] were studied using tail immersion test on rats and compared to PCP. The results showed that, II can produce more analgesic effects in the tail immersion test (as a model of acute thermal pain) in comparison to the PCP with a marked significant increase in tail immersion latency (15, 40 and 45 min after injection) but for III, only slight analgesic effects (15, 35 and 40 min after injection) was seen (without significant differences between pain thresholds). ECV Editio Cantor Verlag.
- Ahmadi, Abbas,Khalili, Mohsen,Abbassi, Sara,Javadi, Mozhdeh,Mahmoudi, Ali,Hajikhani, Ramin
-
experimental part
p. 202 - 206
(2009/07/19)
-
- Syntheses of fluorinated phencyclidine analogs
-
Syntheses of several fluorinated phencyclidine (PCP) analogs are described. These compounds are being used to probe PCP binding sites on N-methyl-D-aspartate (NMDA) receptors. The compounds were prepared in good yields by Grignard reaction of appropriate fluorine substituted bromobenzene with carbonitrile intermediates. Syntheses of the known compound 1-[1-(3-fluorophenyl) cyclohexyl]piperidine, and the novel compounds 1-[1-(4-fluorophenyl)cyclohexyl]piperidine, 1-[1-(3-fluorophenyl) cyclohexyl]pyrrolidine, and 1-[1-(4-fluorophenyl)cyclohexyl]pyrrolidine are reported.
- Ogunbadeniyi, Alaba M.,Adejare, Adeboye
-
-
- Preparation and study of derivatives and analogues of the phencyclidine molecule possessing immunosuppressive properties in vitro
-
Derivatives and analogues of the phencyclidine molecule (1-phenyl 1-(1-piperidino) cyclohexane or PCP) were prepared to investigate their immunosuppressive potency and to define the physicochemical parameters which may influence this activity recently demonstrated for PCP.Most of the tested molecules are more effective than PCP itself.In spite of lack of quantitative data, the biological activity appears to be dependent upon 3 parameters: conformation, lipophilicity, and the empirical Hammett's parameters.The homogeneous conformations with a high lipophilicity were the most immunosuppressive.Interestingly, such structures appeared to be of weak potency on the PCP receptor in the CNS.
- Ilagouma, A. T.,Dornand, J.,Liu, C. F.,Zenone, F.,Mani, J. C.,Kamenka, J. M.
-
p. 609 - 615
(2007/10/02)
-
- Phencyclidine compounds and assays for its determination
-
Novel oxime derivatives of phencyclidine are provided as precursors for conjugating proteins, either antigenic for the preparation of antibodies or enzymatic for the preparation of enzyme conjugates, which antibodies and enzyme conjugates find use as reagents in immunoassays. The combination of antibodies and enzyme conjugates provide for sensitive, accurate, rapid assays for phencyclidine without interference from commonly administered drugs, such as dextromethorphan, demerol and chlorpromazine.
- -
-
-
- Phencyclidine conjugates to antigenic proteins and enzymes
-
Phencylidine, PCP, derivatives having a non-oxo carbonyl functionality linked directly or through a linking group to the phenyl ring are provided for conjugation to antigenic compositions, particularly poly(amino acids), and enzymes. The antigenic conjugates are employed for the production of antibodies, which find particular use in immunoassays for the determination of phencyclidine, while the enzyme conjugate finds use in a homogeneous enzyme immunoassay for the determination of phencyclidine.
- -
-
-
- 1-(3,4-DICHLOROBENZAMIDOMETHYL)-CYCLOHEXYLDIMETHYLAMINE
-
Compounds of the general formula I: EQU1 in which R1 - R4 which may be the same or different represent hydrogen atoms, or C1-6 straight or branched chain alkyl, alkenyl or alkynyl group or an alkyl group substituted by a cycloalkyl group, or represents a cycloalkyl, alkoxycarbonyl, aryl, arakyl, acyl (which includes anylsulphonyl) groups in which the alkyl group or the alkyl portion of the aralkyl group may be substituted with one or more hydroxy or esterified hydroxy groups and in which the aryl groups or the aryl portion of the acyl or aralkyl group may be substituted by one or more halogen atoms, alkyl groups, hydroxy groups, alkoxy groups, trifluoromethyl, nitro, amino or dialkylamino groups, and in which R5 - R8 which may be the same or different represent hydrogen atoms or alkyl groups except that not all groups may be hydrogen, or R5 and R6 or R7 and R8 together represent a carbonyl (=O) oxygen and in any of the pairs of groups R1 /R2, R3 /R4, R5 /R6 and R7 /R8 may represent a carbocyclic or heterocyclic ring system optionally substituted by lower alkyl or aryl groups, said ring being saturated or unsaturated. These compounds have utility as oral analgesics.
- -
-
-