DMBMPP

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DMBMPP
SS9b structure.png
Clinical data
Synonyms Juncosamine
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
Formula C21H26BrNO3
Molar mass 420.34 g/mol
3D model (JSmol)

DMBMPP, or 2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine, is a 2-benzylpiperidine analog of the hallucinogenic N-benzylphenethylamine 25B-NBOMe and was discovered in 2011 by Jose Juncosa in the group of David E. Nichols at Purdue University.[1][2] DMBPP differs from 25B-NBOMe by having a piperidine ring conformed to the amine, making for a more rigid molecular structure than that of the open-chain 25B-NBOMe. The presence of the piperidine ring introduces two stereocenters, thus, four stereoisomers of this compound can be made.

Pharmacology[edit]

The (S,S)-isomer (2S,6S-DMBMPP) is the most interesting scientifically as it is the most selective agonist for the human 5-HT2A receptor yet discovered, with a Ki of 2.5 nM at the human 5-HT2A receptor and with 124-fold selectivity for 5-HT2A over the structurally similar 5-HT2C-receptor.[3] Together with 25CN-NBOH,[4] 2S,6S-DMBMPP is the only known 5-HT2A agonist to exhibit this level of selectivity.

Ligand Ki ± SEM (nM) Ki ± SEM (nM) Ki ± SEM (nM)
[3H] ketanserin [3H] mesulergine fold selectivity
h5-HT2A h5-HT2C h5-HT2C/h5-HT2A
2C-B 6.0 ± 0.3 23.8 ± 2.6 9.5
25B-NBOMe 0.19 ± 0.01 4.0 ± 0.4 21
(±)-DMBMPP 5.3 ± 0.3 520 ± 22 98
(S,S)-(−)-DMBMPP 2.5 ± 0.1 310 ± 42 124
(R,R)-(+)-DMBMPP 2,100 ± 171 28,600 ± 4700 27

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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 3547484Freely accessible. PMID 23336049. 
  3. ^ 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 3547484Freely accessible. PMID 23336049. 
  4. ^ 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 3963123Freely accessible. PMID 24397362.