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| {{Short description|Chemical compound}} | |||
| {{cs1 config|name-list-style=vanc|display-authors=6}} | |||
| {{Drugbox | {{Drugbox | ||
| | verifiedrevid = |
| verifiedrevid = 442227725 | ||
| | IUPAC_name = 2-benzylpiperidine | | IUPAC_name = 2-benzylpiperidine | ||
| | image = 2-Benzylpiperidine.png | | image = 2-Benzylpiperidine.png | ||
| | image2 = 2-benzylpiperidine3d.png | |||
| <!--Clinical data--> | <!--Clinical data--> | ||
| Line 9: | Line 12: | ||
| | legal_status = Uncontrolled | | legal_status = Uncontrolled | ||
| | routes_of_administration = Oral | | routes_of_administration = Oral | ||
| | class = ] | |||
| <!--Pharmacokinetic data--> | <!--Pharmacokinetic data--> | ||
| Line 18: | Line 22: | ||
| <!--Identifiers--> | <!--Identifiers--> | ||
| | CAS_number = 32838-55-4 | | CAS_number = 32838-55-4 | ||
| | UNII_Ref = {{fdacite|correct|FDA}} | |||
| | UNII = | |||
| | ATC_prefix = none | | ATC_prefix = none | ||
| | ATC_suffix = | | ATC_suffix = | ||
| Line 26: | Line 32: | ||
| <!--Chemical data--> | <!--Chemical data--> | ||
| | C=12 | H=17 | N=1 | | C=12 | H=17 | N=1 | ||
| | molecular_weight = 175.27 g/mol | |||
| | smiles = C1CCNC(C1)CC2=CC=CC=C2 | | smiles = C1CCNC(C1)CC2=CC=CC=C2 | ||
| | InChI = 1/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 | |||
| | InChIKey = ITXCORRITGNIHP-UHFFFAOYAB | |||
| | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | ||
| | StdInChI = 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 | | StdInChI = 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 | ||
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| }} | }} | ||
| '''2-Benzylpiperidine''' is a ] ] of the ] |
'''2-Benzylpiperidine''' is a ] ] of the ]] family. It is similar in ] to certain other stimulants such as ] and ]. However, it is far less ] as a ] in comparison.<ref name="Yadav-SamudralaEltit2019" /><ref name="Yadav2019" /><ref name="KimDeutschYe2007" /> The drug is little used as a stimulant, with its main use being as a ] in the ] of other drugs.<ref name="AblordeppeyFischerLaw2002">{{cite journal | vauthors = Ablordeppey SY, Fischer JB, Law H, Glennon RA | title = Probing the proposed phenyl-A region of the sigma-1 receptor | journal = Bioorganic & Medicinal Chemistry | volume = 10 | issue = 8 | pages = 2759–2765 | date = August 2002 | pmid = 12057665 | doi = 10.1016/S0968-0896(02)00096-2 }}</ref><ref name="ÁgaiProszenyákTárkányi2004">{{cite journal | vauthors = Ágai B, Proszenyák A, Tárkányi G, Vida L, Faigl F | title = Convenient, Benign and Scalable Synthesis of 2- and 4-Substituted Benzylpiperidines. | journal = European Journal of Organic Chemistry | date = 2004 | volume = 2004 | issue = 17 | pages = 3623–3632 | doi = 10.1002/ejoc.200400215 }}</ref><ref name="US6124317">{{cite patent | url = http://www.google.com/patents?id=1H8FAAAAEBAJ&dq=6124317 | inventor = Bigge CF, Keana JR, Cai SX, Weber E, Woodward R, Lan NC, Guzikowski AP | title = 2-substituted piperidine analogs and their use as subtype-selective NMDA receptor antagonists. | country = US | number = 6124317 }}</ref> | ||
| == |
== Pharmacology == | ||
| The ] (K<sub>i</sub>) of 2-benzylpiperidine for the ] (DAT) has been reported to be 6,360{{nbsp}}nM and its ] ({{Abbr|IC<sub>50</sub>|half-maximal effective concentration}}) of the DAT has been reported to be 3,780 to 8,800{{nbsp}}nM.<ref name="Yadav-SamudralaEltit2019">{{cite journal | vauthors = Yadav-Samudrala BJ, Eltit JM, Glennon RA | title = Synthetic Cathinone Analogues Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors | journal = ACS Chem Neurosci | volume = 10 | issue = 9 | pages = 4043–4050 | date = September 2019 | pmid = 31369229 | doi = 10.1021/acschemneuro.9b00284 | url = | quote = Compound 5 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.}}</ref><ref name="Yadav2019">{{cite web | vauthors = Yadav BJ | title=Understanding Structure-Activity Relationship Of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate | website=VCU Scholars Compass | date=16 July 2019 | url=https://scholarscompass.vcu.edu/etd/5955/ | access-date=9 December 2024 | quote=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 DA reuptake potency by 38-fold (IC50 = 8800 nM) as compared to tMP (70) (IC50 =75 and 230 nM, binding affinity and 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.}}</ref><ref name="KimDeutschYe2007">{{cite journal | vauthors = Kim DI, Deutsch HM, Ye X, Schweri MM | title = Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 11 | pages = 2718–2731 | date = May 2007 | pmid = 17489581 | doi = 10.1021/jm061354p }}</ref> These values were 85-fold and 53- to 38-fold lower than those of methylphenidate, respectively.<ref name="Yadav-SamudralaEltit2019" /><ref name="Yadav2019" /><ref name="KimDeutschYe2007" /> It produced 36% inhibition of binding to the ] (NET) and 22% inhibition of binding to the ] (SERT) at a concentration of 10,000{{nbsp}}nM.<ref name="KimDeutschYe2007" /> However, ] 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.<ref name="Yadav-SamudralaEltit2019" /> In another older study, 2-benzylpiperidine was reported to be similarly potent to ] in terms of ].<ref name="FerrisTang1979">{{cite journal | vauthors = Ferris RM, Tang FL | title = Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l-norepinephrine and dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 210 | issue = 3 | pages = 422–428 | date = September 1979 | pmid = 39160 | quote = 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). }}</ref> | |||
| == Analogs == | |||
| ]s of 2-benzylpiperidine, such as the ]-like derivative ] and its 4-methyl, 4-halo, and 3,4-dichloro analogues, have been synthesized and have been found to be much more potent as ]s.<ref name="Yadav-SamudralaEltit2019" /> Another analogue of 2-benzylpiperidine, ], is also more potent as a monoamine reuptake inhibitor in comparison, with higher affinities for the ]s and ~8-fold higher functional inhibition of the DAT.<ref name="KimDeutschYe2007" /> | |||
| ==See also== | |||
| * ] | * ] | ||
| * ] | * ] | ||
| == |
==References== | ||
| {{Reflist}} | {{Reflist}} | ||
| {{Stimulants}} | {{Stimulants}} | ||
| {{Monoamine reuptake inhibitors}} | |||
| {{Adrenergics}} | |||
| {{Dopaminergics}} | |||
| ⚫ | ] | ||
| ] | |||
| {{DEFAULTSORT:Benzylpiperidine, 2-}} | {{DEFAULTSORT:Benzylpiperidine, 2-}} | ||
| ] | |||
| ] | |||
| ] | |||
| ⚫ | ] | ||
Latest revision as of 18:50, 13 December 2024
Chemical compoundPharmaceutical compound
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 | |
| Clinical data | |
|---|---|
| Routes of administration | Oral |
| Drug class | Dopamine reuptake inhibitor |
| ATC code |
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| Legal status | |
| Legal status |
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| Identifiers | |
IUPAC name
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| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.046.581  |
| Chemical and physical data | |
| Formula | C12H17N |
| Molar mass | 175.275 g·mol |
| 3D model (JSmol) | |
SMILES
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InChI
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| (verify) | |
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.
Pharmacology
The affinity (Ki) of 2-benzylpiperidine for the dopamine transporter (DAT) has been reported to be 6,360 nM and its functional inhibition (IC50) of the DAT has been reported to be 3,780 to 8,800 nM. 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 10,000 nM. 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.
Analogs
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
References
- ^ Yadav-Samudrala BJ, Eltit JM, Glennon RA (September 2019). "Synthetic Cathinone Analogues Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors". ACS Chem Neurosci. 10 (9): 4043–4050. doi:10.1021/acschemneuro.9b00284. PMID 31369229.
Compound 5 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 (16 July 2019). "Understanding Structure-Activity Relationship Of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate". VCU Scholars Compass. Retrieved 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 DA reuptake potency by 38-fold (IC50 = 8800 nM) as compared to tMP (70) (IC50 =75 and 230 nM, binding affinity and 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 (May 2007). "Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate". Journal of Medicinal Chemistry. 50 (11): 2718–2731. doi:10.1021/jm061354p. PMID 17489581.
- Ablordeppey SY, Fischer JB, Law H, Glennon RA (August 2002). "Probing the proposed phenyl-A region of the sigma-1 receptor". Bioorganic & Medicinal Chemistry. 10 (8): 2759–2765. doi:10.1016/S0968-0896(02)00096-2. PMID 12057665.
- Ágai B, Proszenyák A, Tárkányi G, Vida L, Faigl F (2004). "Convenient, Benign and Scalable Synthesis of 2- and 4-Substituted Benzylpiperidines". European Journal of Organic Chemistry. 2004 (17): 3623–3632. doi:10.1002/ejoc.200400215.
- US 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."
- Ferris RM, Tang FL (September 1979). "Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l-norepinephrine and dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus". The Journal of Pharmacology and Experimental Therapeutics. 210 (3): 422–428. PMID 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).