DMBMPP

DMBMPP
Clinical data
Other names	Juncosamine; 2-(2,5-Dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine
Drug class	Selective serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code	None;
Identifiers
	IUPAC name 2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine;
CAS Number	1391499-52-7 ;
PubChem CID	72683323;
ChemSpider	59718542;
UNII	7H5TDL9Y6X;
Chemical and physical data
Formula	C21H26BrNO3
Molar mass	420.347 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC(C=C(Br)C(OC)=C1)=C1C[C@@H]2CCC[C@@H](C3=C(OC)C=CC=C3)N2;
	InChI InChI=1S/C21H26BrNO3/c1-24-19-10-5-4-8-16(19)18-9-6-7-15(23-18)11-14-12-21(26-3)17(22)13-20(14)25-2/h4-5,8,10,12-13,15,18,23H,6-7,9,11H2,1-3H3/t15-,18-/m0/s1; Key:KMVGLBONODPTDY-YJBOKZPZSA-N;

DMBMPP, also known as juncosamine or as 2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine, is a highly selective serotonin 5-HT_2A receptor agonist and 2-benzylpiperidine analogue of the serotonergic psychedelic 25B-NBOMe which is used in scientific research.^[1]^[2]^[3]^[4]

^ Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 866–867. ISBN 978-3-03788-700-4. OCLC 858805226. Retrieved 31 January 2025.
^ Halberstadt AL (2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Current Topics in Behavioral Neurosciences. 32: 283–311. doi:10.1007/7854_2016_64. PMID 28097528. NBOMes exhibit a high degree of conformational flexibility and could potentially adopt a range of active binding poses. In order to identify the active conformation, Nichols and colleagues synthesized a series of rigid analogues of 25B-NBOMe [54]. Of the nine structurally constrained compounds tested, ()-trans-DMBMPP (Fig. 7) was the most potent, binding to human 5-HT2A receptors with a Ki of 5.3 nM. Interestingly, the affinity of ()-trans-DMBMPP for human 5-HT2C sites is significantly lower in comparison, making it 98-fold selective for 5-HT2A receptors. The (S,S) enantiomer of DMBMPP, resolved by derivatization with a chiral auxiliary, has even higher 5-HT2A affinity (Ki ¼ 2.5 nM) and is reportedly 124-fold selective for 5-HT2A vs. 5-HT2C receptors. By contrast, (R,R)-DMBMPP has μM affinity for 5-HT2A receptors (Fig. 7). It appears that the structural configuration of (S,S)-DMBMPP closely mirrors the active binding conformation of NBOMes. [...] Fig. 7 Structures of racemic trans-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine (-trans-DMBMPP) and its S,S and R,R enantiomers. Binding affinities were assessed at human 5-HT2A and 5-HT2C receptors labeled with [3 H]ketanserin and [3 H]mesulergine, respectively [54].
^ Juncosa JI (2011-05-07). Organic synthesis combined with molecular modeling: A powerful approach to map the functional topography of dopamine and serotonin receptors (Ph.D. thesis). Purdue University.
^ Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, et al. (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.

[Trachsel_2013-1] Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 866–867. ISBN 978-3-03788-700-4. OCLC 858805226. Retrieved 31 January 2025.

[Halberstadt_2017-2] Halberstadt AL (2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Current Topics in Behavioral Neurosciences. 32: 283–311. doi:10.1007/7854_2016_64. PMID 28097528. NBOMes exhibit a high degree of conformational flexibility and could potentially adopt a range of active binding poses. In order to identify the active conformation, Nichols and colleagues synthesized a series of rigid analogues of 25B-NBOMe [54]. Of the nine structurally constrained compounds tested, ()-trans-DMBMPP (Fig. 7) was the most potent, binding to human 5-HT2A receptors with a Ki of 5.3 nM. Interestingly, the affinity of ()-trans-DMBMPP for human 5-HT2C sites is significantly lower in comparison, making it 98-fold selective for 5-HT2A receptors. The (S,S) enantiomer of DMBMPP, resolved by derivatization with a chiral auxiliary, has even higher 5-HT2A affinity (Ki ¼ 2.5 nM) and is reportedly 124-fold selective for 5-HT2A vs. 5-HT2C receptors. By contrast, (R,R)-DMBMPP has μM affinity for 5-HT2A receptors (Fig. 7). It appears that the structural configuration of (S,S)-DMBMPP closely mirrors the active binding conformation of NBOMes. [...] Fig. 7 Structures of racemic trans-2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine (-trans-DMBMPP) and its S,S and R,R enantiomers. Binding affinities were assessed at human 5-HT2A and 5-HT2C receptors labeled with [3 H]ketanserin and [3 H]mesulergine, respectively [54].

[Juncosa_2011-3] Juncosa JI (2011-05-07). Organic synthesis combined with molecular modeling: A powerful approach to map the functional topography of dopamine and serotonin receptors (Ph.D. thesis). Purdue University.

[Juncosa_2013-4] Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, et al. (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.

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