2C-B-morpholine

2C-B-morpholine
Clinical data
Other names	2-(4-Bromo-2,5-dimethoxyphenyl)morpholine
Drug class	Serotonin receptor modulator; Serotonin 5-HT2A receptor ligand
ATC code	None;
Identifiers
	IUPAC name 2-(4-bromo-2,5-dimethoxyphenyl)morpholine;
CAS Number	807631-07-8;
PubChem CID	11429275;
ChemSpider	9604151;
ChEMBL	ChEMBL191154;
Chemical and physical data
Formula	C12H16BrNO3
Molar mass	302.168 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC1=CC(=C(C=C1C2CNCCO2)OC)Br;
	InChI InChI=1S/C12H16BrNO3/c1-15-10-6-9(13)11(16-2)5-8(10)12-7-14-3-4-17-12/h5-6,12,14H,3-4,7H2,1-2H3; Key:OUTZYBJUJMETRJ-UHFFFAOYSA-N;

2C-B-morpholine, also known as 2-(4-bromo-2,5-dimethoxyphenyl)morpholine, is a serotonin receptor modulator of the phenylmorpholine (phenmetrazine) and cyclized phenethylamine groups.^[1] It is a ligand of the serotonin 5-HT_2A receptor, with an affinity of 20.6 nM and an E_maxTooltip maximal efficacy of 4%.^[1] The drug showed 103-fold lower affinity for this receptor than R(–)-DOB and had minimal agonist activity (with R(–)-DOB having an E_max of 51% in the assay), so for practical purposes would act as an antagonist at the 5-HT_2A receptor under most circumstances, despite being technically classified as a partial agonist.^[1] 2C-B-morpholine was first described in the scientific literature by Richard Glennon and colleagues by 2004.^[1]

References

^ ^a ^b ^c ^d Glennon RA, Bondarev ML, Khorana N, Young R, May JA, Hellberg MR, et al. (November 2004). "Beta-oxygenated analogues of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane". Journal of Medicinal Chemistry. 47 (24): 6034–6041. doi:10.1021/jm040082s. PMID 15537358. One of the first compounds prepared and examined in this investigation was morpholine analogue 2. Compound 2 bears an ether oxygen atom at the benzylic position that is tethered to the terminal amine. However, its 5-HT2A affinity (Ki) 20.6 nM) is 100-fold lower than that of R(-)DOB (Ki) 0.2 nM), and its agonist efficacy in the 5-HT2-mediated calcium mobilization assay is minimal (Table 1). There are several possible explanations for these unfavorable findings. Apart from the molecule possessing a chiral center, the ether oxygen atom might not be tolerated by the receptor and/or the added ethylene "bridge" might not be readily accommodated by the receptor and its presence detracts from affinity. A more plausible explanation, based on prior structure-affinity investigations, is that the secondary amine of 2 contributes to decreased affinity. That is, we have previously shown that addition of small N-alkyl substituents can reduce the 5-HT2A receptor affinity of DOB and DOB-related compounds.16,17

External links

2C-B-morpholine - Isomer Design

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[Glennon_2004-1] Glennon RA, Bondarev ML, Khorana N, Young R, May JA, Hellberg MR, et al. (November 2004). "Beta-oxygenated analogues of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane". Journal of Medicinal Chemistry. 47 (24): 6034–6041. doi:10.1021/jm040082s. PMID 15537358. One of the first compounds prepared and examined in this investigation was morpholine analogue 2. Compound 2 bears an ether oxygen atom at the benzylic position that is tethered to the terminal amine. However, its 5-HT2A affinity (Ki) 20.6 nM) is 100-fold lower than that of R(-)DOB (Ki) 0.2 nM), and its agonist efficacy in the 5-HT2-mediated calcium mobilization assay is minimal (Table 1). There are several possible explanations for these unfavorable findings. Apart from the molecule possessing a chiral center, the ether oxygen atom might not be tolerated by the receptor and/or the added ethylene "bridge" might not be readily accommodated by the receptor and its presence detracts from affinity. A more plausible explanation, based on prior structure-affinity investigations, is that the secondary amine of 2 contributes to decreased affinity. That is, we have previously shown that addition of small N-alkyl substituents can reduce the 5-HT2A receptor affinity of DOB and DOB-related compounds.16,17

[1]

See also

References

External links