2-Benzylpiperidine

Chemical compound vanc 6 442227725 2-benzylpiperidine 2-Benzylpiperidine.svg skin-invert-image 200px 2-benzylpiperidine3d.png bg-transparent 250px Uncontrolled Oral Dopamine reuptake inhibitor correct CAS 32838-55-4 correct FDA 8M5DNQ89DJ none 118004 correct chemspider 105447 12 17 1 C1CCNC(C1)CC2=CC=CC=C2 correct chemspider 1S/C12H17N/c1-2-6-11(7-3-1)10-12-8-4-5-9-13-12/h1-3,6-7,12-13H,4-5,8-10H2 correct chemspider ITXCORRITGNIHP-UHFFFAOYSA-N 2-Benzylpiperidine is a stimulant drug of the arylpiperidine family. It is similar in structure to certain other stimulants such as methylphenidate and desoxypipradrol. However, it is far less potent as a monoamine reuptake inhibitor in comparison. The drug is little used as a stimulant, with its main use being as a synthetic intermediate in the manufacture of other drugs. Ablordeppey SY, Fischer JB, Law H, Glennon RA Probing the proposed phenyl-A region of the sigma-1 receptor Bioorganic & Medicinal Chemistry 10 8 2759–2765 August 2002 12057665 10.1016/S0968-0896(02)00096-2 Ágai B, Proszenyák A, Tárkányi G, Vida L, Faigl F Convenient, Benign and Scalable Synthesis of 2- and 4-Substituted Benzylpiperidines. European Journal of Organic Chemistry 2004 2004 17 3623–3632 10.1002/ejoc.200400215 http://www.google.com/patents?id=1H8FAAAAEBAJ&dq=6124317 Bigge CF, Keana JR, Cai SX, Weber E, Woodward R, Lan NC, Guzikowski AP 2-substituted piperidine analogs and their use as subtype-selective NMDA receptor antagonists. US 6124317 Pharmacology The affinity (Ki) of 2-benzylpiperidine for the dopamine transporter (DAT) has been reported to be 6,360nM and its functional inhibition (IC50 half-maximal effective concentration) of the DAT has been reported to be 3,780 to 8,800nM. Yadav-Samudrala BJ, Eltit JM, Glennon RA Synthetic Cathinone Analogues Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors ACS Chem Neurosci 10 9 4043–4050 September 2019 31369229 10.1021/acschemneuro.9b00284 Compound 5 [(2-benzylpiperidine)] has also, apparently, been previously prepared and examined as a DAT reuptake inhibitor by Kim et al.6 However, there is a potential problem. Although Kim et al.6 showed the correct chemical structure for 2-benzylpiperidine, their experimental writeup suggests they might have inadvertently prepared 2-phenylpiperidine. Furthermore, their melting point for the target is different from that previously reported by others for the target compound.23,24 Obviously, apart from the different melting point, this might have been a typographical error. Yadav BJ Understanding Structure-Activity Relationship Of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate VCU Scholars Compass 16 July 2019 https://scholarscompass.vcu.edu/etd/5955/ 9 December 2024 8 Complete removal of the ester of tMP (i.e., 2-benzylpiperidine, 130) reduced the binding affinity at DAT by 85-fold (IC50 = 6360 nM) and reduced [ 3H]DA reuptake potency by 38-fold (IC50 = 8800 nM) as compared to tMP (70) (IC50 =75 and 230 nM, binding affinity and [ 3H]DA uptake, respectively).125 [...] We also showed that the carbonyl oxygen atom of 161 is not important for the compound to act as a DAT reuptake inhibitor as our descarbonyl analog (2-benzylpiperidine, 169) retained activity; however, the carbonyl oxygen atom helps to improve the potency at DAT as a reuptake inhibitor. Kim DI, Deutsch HM, Ye X, Schweri MM Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate Journal of Medicinal Chemistry 50 11 2718–2731 May 2007 17489581 10.1021/jm061354p These values were 85-fold and 53- to 38-fold lower than those of methylphenidate, respectively. It produced 36% inhibition of binding to the norepinephrine transporter (NET) and 22% inhibition of binding to the serotonin transporter (SERT) at a concentration of 10,000nM. However, 2-phenylpiperidine might have actually been assayed by mistake in one of the two studies that reported the preceding values, and so some of the values might be incorrect. In another older study, 2-benzylpiperidine was reported to be similarly potent to dextroamphetamine in terms of norepinephrine reuptake inhibition. Ferris RM, Tang FL Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l-[3H]norepinephrine and [3H]dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus The Journal of Pharmacology and Experimental Therapeutics 210 3 422–428 September 1979 39160 [...] removal of the additional phenyl ring of deoxypipradrol or the carbomethoxy group of methylphenidate yields 2-benzylpiperidine which contains the intact piperidine ring and is as potent as S-(+)-amphetamine as an inhibitor of norepinephrine uptake into synaptic vesicles (unpublished observations). [...] Analogues and derivatives Derivatives of 2-benzylpiperidine, such as the cathinone-like derivative α-keto-2-benzylpiperidine and its 4-methyl, 4-halo, and 3,4-dichloro analogues, have been synthesized and have been found to be much more potent as dopamine reuptake inhibitors. Another analogue of 2-benzylpiperidine, 3-phenylpiperidine, is also more potent as a monoamine reuptake inhibitor in comparison, with higher affinities for the monoamine transporters and ~8-fold higher functional inhibition of the DAT. See also 4-Benzylpiperidine 1-Benzylpiperazine References Category:2-Piperidinyl compounds Category:Dopamine reuptake inhibitors Category:Stimulants