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The 25-NB compounds are mostly ''N''-benzylphenethylamines,<ref name="pmid28097528" /> though in some cases the phenyl ring of the N-benzyl group is replaced by other heterocycles such as [[thiophene]], [[pyridine]], [[furan]], [[tetrahydrofuran]], [[benzodioxole]] or [[naphthalene]], among others.<ref>{{cite journal | url=https://docs.lib.purdue.edu/dissertations/AAI3287241/ | title=Towards a biophysical understanding of hallucinogen action | pages=1–176 | journal=Dissertation | date=2007 | author=Michael Robert Braden}}</ref><ref>Nichols DE. Structure-activity relationships of serotonin 5-HT2A agonists. ''WIREs Membr. Transp. Signal'', 2012;1(5):559-579. {{doi|10.1002/wmts.42}}</ref>
The 25-NB compounds are mostly ''N''-benzylphenethylamines,<ref name="pmid28097528" /> though in some cases the phenyl ring of the N-benzyl group is replaced by other heterocycles such as [[thiophene]], [[pyridine]], [[furan]], [[tetrahydrofuran]], [[benzodioxole]] or [[naphthalene]], among others.<ref>{{cite journal | url=https://docs.lib.purdue.edu/dissertations/AAI3287241/ | title=Towards a biophysical understanding of hallucinogen action | pages=1–176 | journal=Dissertation | date=2007 | author=Michael Robert Braden}}</ref><ref>Nichols DE. Structure-activity relationships of serotonin 5-HT2A agonists. ''WIREs Membr. Transp. Signal'', 2012;1(5):559-579. {{doi|10.1002/wmts.42}}</ref>


Generally speaking, they have [[methoxy group]]s at the 2 and 5 positions of the [[phenyl ring]], a [[substituent|substitution]] such as a [[halogen]] or [[alkyl group]] at the 4 position of the phenyl ring, and a methoxy or other substitution (e.g., [[hydroxyl group|hydroxyl]], [[fluorine|fluoro]]) at the 2 position of the ''N''-[[benzyl ring]].<ref name="pmid28097528" /> More rarely, other substitution patterns may be present <ref>Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL. 5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism. ''ACS Chem Neurosci''. 2016 Nov 16;7(11):1614-1619. {{pmid|27564969}} {{doi|10.1021/acschemneuro.6b00265}}</ref> (see e.g. [[NBOMe-mescaline]], [[25G-NBOMe]], [[2CBFly-NBOMe]], [[25C-NB3OMe]]). They differ from the 2C series by the presence of the ''N''-benzyl [[moiety (chemistry)|moiety]].<ref name="pmid28097528" />
Generally speaking, they have [[methoxy group]]s at the 2 and 5 positions of the [[phenyl ring]], a [[substituent|substitution]] such as a [[halogen]] or [[alkyl group]] at the 4 position of the phenyl ring, and a methoxy or other substitution (e.g., [[hydroxyl group|hydroxyl]], [[fluorine|fluoro]]) at the 2 position of the ''N''-[[benzyl ring]].<ref name="pmid28097528" /> More rarely, other substitution patterns may be present <ref>Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL. 5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism. ''ACS Chem Neurosci''. 2016 Nov 16;7(11):1614-1619. {{pmid|27564969}} {{doi|10.1021/acschemneuro.6b00265}}</ref><ref>Prabhakaran J, Solingapuram Sai KK, Zanderigo F, Rubin-Falcone H, Jorgensen MJ, Kaplan JR, Tooke KI, Mintz A, Mann JJ, Kumar JSD. In vivo evaluation of [18F]FECIMBI-36, an agonist 5-HT2A/2C receptor PET radioligand in nonhuman primate. ''Bioorg Med Chem Lett''. 2017 Jan 1;27(1):21-23. {{pmid|27889455}} {{doi|10.1016/j.bmcl.2016.11.043}}</ref> (see e.g. [[NBOMe-mescaline]], [[25G-NBOMe]], [[2CBFly-NBOMe]], [[25C-NB3OMe]]). They differ from the 2C series by the presence of the ''N''-benzyl [[moiety (chemistry)|moiety]].<ref name="pmid28097528" />


Rarely an alpha-methyl group is present making them N-benzyl amphetamines rather than N-benzyl phenethylamines, but this greatly reduces potency and activity. However in some cases where a side chain methyl group is cyclised back to the ring (e.g. in [[2CBCB-NBOMe]]) or links the two alpha positions (e.g. in [[DMBMPP]]), this can improve selectivity for the 5-HT<sub>2A</sub> receptor subtype.<ref>{{cite journal | vauthors = Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE | title = Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands | journal = ACS Chemical Neuroscience | volume = 4 | issue = 1 | pages = 96–109 | date = January 2013 | pmid = 23336049 | pmc = 3547484 | doi = 10.1021/cn3000668 }}</ref>
Rarely an alpha-methyl group is present making them N-benzyl amphetamines rather than N-benzyl phenethylamines, but this greatly reduces potency and activity. However in some cases where a side chain methyl group is cyclised back to the ring (e.g. in [[2CBCB-NBOMe]]) or links the two alpha positions (e.g. in [[DMBMPP]]), this can improve selectivity for the 5-HT<sub>2A</sub> receptor subtype.<ref>{{cite journal | vauthors = Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE | title = Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands | journal = ACS Chemical Neuroscience | volume = 4 | issue = 1 | pages = 96–109 | date = January 2013 | pmid = 23336049 | pmc = 3547484 | doi = 10.1021/cn3000668 }}</ref>

Revision as of 04:33, 27 April 2019

25I-NBOMe, the most well-known 25-NB derivative.

The 25-NB (25x-NBx) series, sometimes alternatively referred to as the NBOMe compounds, is a family of serotonergic psychedelics.[1] They are substituted phenethylamines and were derived from the 2C family.[1] They act as selective agonists of the serotonin 5-HT2A receptor.[2][3][4][5][6][7][8] The 25-NB family is unique relative to other classes of psychedelics in that they are, generally speaking, extremely potent and highly selective for the 5-HT2A receptor.[1]

Chemical Structure

The 25-NB compounds are mostly N-benzylphenethylamines,[1] though in some cases the phenyl ring of the N-benzyl group is replaced by other heterocycles such as thiophene, pyridine, furan, tetrahydrofuran, benzodioxole or naphthalene, among others.[9][10]

Generally speaking, they have methoxy groups at the 2 and 5 positions of the phenyl ring, a substitution such as a halogen or alkyl group at the 4 position of the phenyl ring, and a methoxy or other substitution (e.g., hydroxyl, fluoro) at the 2 position of the N-benzyl ring.[1] More rarely, other substitution patterns may be present [11][12] (see e.g. NBOMe-mescaline, 25G-NBOMe, 2CBFly-NBOMe, 25C-NB3OMe). They differ from the 2C series by the presence of the N-benzyl moiety.[1]

Rarely an alpha-methyl group is present making them N-benzyl amphetamines rather than N-benzyl phenethylamines, but this greatly reduces potency and activity. However in some cases where a side chain methyl group is cyclised back to the ring (e.g. in 2CBCB-NBOMe) or links the two alpha positions (e.g. in DMBMPP), this can improve selectivity for the 5-HT2A receptor subtype.[13]

List of 25-NB derivatives

General structure of 25-NB derivatives, where R is usually 2,5-dimethoxy-4-(alkyl or halogen), R1 is usually H but rarely methyl, and Cyc is usually 2-substituted phenyl but can be other heterocycles

This list includes notable compounds representative of most of the structural variations that have been explored in this series, but is by no means exhaustive. Many derivatives invented for scientific study into the structure-activity relationships of 5-HT2 receptor agonists have never appeared as designer drugs, while conversely some derivatives that have appeared as designer drugs are structurally novel and of unknown pharmacological activity (e.g. C30-NBOMe, 5-APB-NBOMe).

Common name Chemical name R R1 Cyc
25B-NB 2,5-dimethoxy-4-bromo H phenyl
25C-NB 2,5-dimethoxy-4-chloro H phenyl
25I-NB 2,5-dimethoxy-4-iodo H phenyl
25I-NMeTh 2,5-dimethoxy-4-iodo H thiophen-2-yl
25I-NMePyr 2,5-dimethoxy-4-iodo H pyridin-2-yl
25I-NMeFur 2,5-dimethoxy-4-iodo H furan-2-yl
25I-NMeTHF 2,5-dimethoxy-4-iodo H tetrahydrofuran-2-yl
25B-NBF 2,5-dimethoxy-4-bromo H 2-fluorophenyl
25B-NBOH 2,5-dimethoxy-4-bromo H 2-hydroxyphenyl
25B-NBOMe 2,5-dimethoxy-4-bromo H 2-methoxyphenyl
25B-NB23DM 2,5-dimethoxy-4-bromo H 2,3-dimethoxyphenyl
25B-NB25DM 2,5-dimethoxy-4-bromo H 2,5-dimethoxyphenyl
25B-NMe7BF 2,5-dimethoxy-4-bromo H benzofuran-7-yl
25B-NMe7Ind 2,5-dimethoxy-4-bromo H indol-7-yl
FECIMBI-36 2,5-dimethoxy-4-bromo H 2-(2-fluoroethoxy)phenyl
DOB-NBOMe 2,5-dimethoxy-4-bromo methyl 2-methoxyphenyl
25C-NB3OMe 2,5-dimethoxy-4-chloro H 3-methoxyphenyl
25C-NB4OMe 2,5-dimethoxy-4-chloro H 4-methoxyphenyl
C30-NBOMe 2,5-dimethoxy-4-chloro H 3,4,5-trimethoxyphenyl
25C-NBF 2,5-dimethoxy-4-chloro H 2-fluorophenyl
25C-NBCl 2,5-dimethoxy-4-chloro H 2-chlorophenyl
25C-NBOH 2,5-dimethoxy-4-chloro H 2-hydroxyphenyl
25C-NBOMe 2,5-dimethoxy-4-chloro H 2-methoxyphenyl
25C-NBOEt 2,5-dimethoxy-4-chloro H 2-ethoxyphenyl
25C-NBOiPr 2,5-dimethoxy-4-chloro H 2-isopropoxyphenyl
25F-NBOMe 2,5-dimethoxy-4-fluoro H 2-methoxyphenyl
25CN-NBOH 2,5-dimethoxy-4-cyano H 2-hydroxyphenyl
25CN-NBOMe 2,5-dimethoxy-4-cyano H 2-methoxyphenyl
25D-NBOMe 2,5-dimethoxy-4-methyl H 2-methoxyphenyl
25D-NBOH 2,5-dimethoxy-4-methyl H 2-hydroxyphenyl
25E-NBOMe 2,5-dimethoxy-4-ethyl H 2-methoxyphenyl
25E-NBOH 2,5-dimethoxy-4-ethyl H 2-hydroxyphenyl
25G-NBOMe 2,5-dimethoxy-3,4-dimethyl H 2-methoxyphenyl
25H-NBOMe 2,5-dimethoxy H 2-methoxyphenyl
25I-NB34MD 2,5-dimethoxy-4-iodo H 3,4-methylenedioxyphenyl
25I-NB3OMe 2,5-dimethoxy-4-iodo H 3-methoxyphenyl
25I-NB4OMe 2,5-dimethoxy-4-iodo H 4-methoxyphenyl
25I-NBF 2,5-dimethoxy-4-iodo H 2-fluorophenyl
25I-NBBr 2,5-dimethoxy-4-iodo H 2-bromophenyl
25I-NBTFM 2,5-dimethoxy-4-iodo H 2-(trifluoromethyl)phenyl
25I-NBMD 2,5-dimethoxy-4-iodo H 2,3-methylenedioxyphenyl
25B-NBMD 2,5-dimethoxy-4-bromo H 2,3-methylenedioxyphenyl
25C-NBMD 2,5-dimethoxy-4-chloro H 2,3-methylenedioxyphenyl
25I-NBOH 2,5-dimethoxy-4-iodo H 2-hydroxyphenyl
25I-NBOMe 2,5-dimethoxy-4-iodo H 2-methoxyphenyl
DOI-NBOMe 2,5-dimethoxy-4-iodo methyl 2-methoxyphenyl
25I-NBMeOH 2,5-dimethoxy-4-iodo H 2-(hydroxymethyl)phenyl
25I-NBAm 2,5-dimethoxy-4-iodo H 2-(carbamoyl)phenyl
25I-NMe7DHBF 2,5-dimethoxy-4-iodo H 2,3-dihydrobenzofuran-7-yl
25I-N2Nap1OH 2,5-dimethoxy-4-iodo H 1-hydroxynaphthalen-2-yl
25I-N3MT2M 2,5-dimethoxy-4-iodo H 3-methoxythiophen-2-yl
25I-N4MT3M 2,5-dimethoxy-4-iodo H 4-methoxythiophen-3-yl
25iP-NBOMe 2,5-dimethoxy-4-isopropyl H 2-methoxyphenyl
25N-NBOMe 2,5-dimethoxy-4-nitro H 2-methoxyphenyl
25P-NBOMe 2,5-dimethoxy-4-propyl H 2-methoxyphenyl
25P-NBOH 2,5-dimethoxy-4-propyl H 2-hydroxyphenyl
25TFM-NBOMe 2,5-dimethoxy-4-(trifluoromethyl) H 2-methoxyphenyl
25T-NBOMe 2,5-dimethoxy-4-(methylthio) H 2-methoxyphenyl
25T2-NBOMe 2,5-dimethoxy-4-(ethylthio) H 2-methoxyphenyl
25T4-NBOMe 2,5-dimethoxy-4-(isopropylthio) H 2-methoxyphenyl
25T7-NBOMe 2,5-dimethoxy-4-(propylthio) H 2-methoxyphenyl
25T7-NBOH 2,5-dimethoxy-4-(propylthio) H 2-hydroxyphenyl
NBOMe-mescaline 3,4,5-trimethoxy H 2-methoxyphenyl
NBOMe-escaline 3,5-dimethoxy-4-ethoxy H 2-methoxyphenyl
MDPEA-NBOMe 3,4-methylenedioxy H 2-methoxyphenyl
Clobenzorex H methyl 2-chlorophenyl
4-EA-NBOMe 4-ethyl methyl 2-methoxyphenyl
5-APB-NBOMe benzofuran-5-yl instead of phenyl methyl 2-methoxyphenyl


Derivatives with atypical structures include:

Legality

United Kingdom

A large number of substances in the 25-NB class are Class A drugs in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971[14] or are otherwise covered by the Psychoactive Substances Act 2016.[15]

See also

References

  1. ^ a b c d e f Halberstadt AL (2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Curr Top Behav Neurosci. 32: 283–311. doi:10.1007/7854_2016_64. PMID 28097528.
  2. ^ Pertz, HH; Rheineck, A; Elz, S (1999-01-01). "N-Benzylated derivatives of the hallucinogenic drugs mescaline and escaline as partial agonists at rat vascular 5-HT2A receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 359: R29.
  3. ^ Heim, Ralf (February 28, 2010). "Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts" (in German). diss.fu-berlin.de. Retrieved 2013-05-10. {{cite web}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  4. ^ Silva, Maria (2009). Theoretical study of the interaction of agonists with the 5-HT2A receptor (Ph.D. thesis). Universität Regensburg. {{cite thesis}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  5. ^ Hansen, Martin (2011). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Ph.D. thesis). University of Copenhagen. {{cite thesis}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  6. ^ Silva ME, Heim R, Strasser A, Elz S, Dove S (January 2011). "Theoretical studies on the interaction of partial agonists with the 5-HT(2A) receptor". Journal of Computer-aided Molecular Design. 25 (1): 51–66. CiteSeerX 10.1.1.688.2670. doi:10.1007/s10822-010-9400-2. PMID 21088982.
  7. ^ Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME. Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology. 2015 Dec;99:546-53. PMID 26318099 doi: 10.1016/j.neuropharm.2015.08.034
  8. ^ Hansen M, Phonekeo K, Paine JS, Leth-Petersen S, Begtrup M, Bräuner-Osborne H, Kristensen JL (March 2014). "Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists". ACS Chemical Neuroscience. 5 (3): 243–9. doi:10.1021/cn400216u. PMC 3963123. PMID 24397362.
  9. ^ Michael Robert Braden (2007). "Towards a biophysical understanding of hallucinogen action". Dissertation: 1–176.
  10. ^ Nichols DE. Structure-activity relationships of serotonin 5-HT2A agonists. WIREs Membr. Transp. Signal, 2012;1(5):559-579. doi:10.1002/wmts.42
  11. ^ Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL. 5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism. ACS Chem Neurosci. 2016 Nov 16;7(11):1614-1619. PMID 27564969 doi:10.1021/acschemneuro.6b00265
  12. ^ Prabhakaran J, Solingapuram Sai KK, Zanderigo F, Rubin-Falcone H, Jorgensen MJ, Kaplan JR, Tooke KI, Mintz A, Mann JJ, Kumar JSD. In vivo evaluation of [18F]FECIMBI-36, an agonist 5-HT2A/2C receptor PET radioligand in nonhuman primate. Bioorg Med Chem Lett. 2017 Jan 1;27(1):21-23. PMID 27889455 doi:10.1016/j.bmcl.2016.11.043
  13. ^ Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE (January 2013). "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chemical Neuroscience. 4 (1): 96–109. doi:10.1021/cn3000668. PMC 3547484. PMID 23336049.
  14. ^ "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". www.legislation.gov.uk.
  15. ^ "Psychoactive Substances Act 2016". www.legislation.gov.uk.


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