11-Methoxyasimilobine

vanc 6 1,11-Dimethoxy-2-hydroxynoraporphine.svg skin-invert-image 200px Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonin 5-HT2C receptor agonist None 175794276 1,11-Dimethoxy-2-hydroxynoraporphine; Compound 16l; Compound S31 1,11-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-2-ol 18 19 1 3 COC1=CC=CC2=C1C3=C4C(C2)NCCC4=CC(=C3OC)O 1S/C18H19NO3/c1-21-14-5-3-4-10-8-12-15-11(6-7-19-12)9-13(20)18(22-2)17(15)16(10)14/h3-5,9,12,19-20H,6-8H2,1-2H3 IRZSTYZUXGRZIR-UHFFFAOYSA-N 11-Methoxyasimilobine, also known as 1,11-dimethoxy-2-hydroxynoraporphine, is a serotonin 5-HT2 receptor agonist of the noraporphine family related to the noraporphine alkaloid asimilobine. Qin W, Zhang B, Wang Q, Jiang G, Cui J, Chen F, Wang L, Chen J, Tian S, Zhen XC, Shui W, Ye N November 2025 Discovery of New N-H Aporphine Derivatives As Brain-Penetrant Gq-Biased 5-HT2C Receptor Agonists and Dual 5-HT2C/5-HT2A Receptor Agonists Journal of Medicinal Chemistry 68 21 23300–23323 10.1021/acs.jmedchem.5c02115 41108743 Most of 2,11-disubstituted derivatives (e.g., 16l, 20n) in series II showed potent 5-HT2CR/5-HT2AR dual agonistic activity. [...] Although 16l exhibited 15.5-fold enhancement in 5-HT2CR potency (EC50 = 2.3 nM, Emax = 100%) and retained weak agonistic activity at 5-HT2BR, it also demonstrated potent 5- HT2AR agonistic activity (EC50 = 18 nM, Emax = 98%), rendering it as a 5-HT2CR and 5-HT2AR dual agonist. [...] Moreover, 16k exhibited minimal agonistic activity toward other members of the 5-HT receptor family, including 5-HT1A, 5-HT1B, 5-HT3, 5-HT4A, 5-HT7A (EC50 > 1 μM; Table S1), similar to that of its 11-methoxy analogue 16l, suggesting 5-HT2R subfamily selectivity of 1,2,11-trisubstituted aporphines. [...] The 1,11-dimethoxy-2-hydroxyl and 2- hydroxyl-11-propoxy derivatives, 16l and 20n, were found to exhibit stronger Gq bias with 6.3-fold (EC50: 9.8 vs 62 nM, p < 0.01) and 13.8-fold (EC50: 5.0 vs 69 nM, p < 0.001) increased potency, respectively, in the Gq assay compared to the βarrestin2 assay (Figure 6D,E). These two compounds also showed higher efficacy in the Gq pathway (118% and 108%) relative to their β-arrestin pathway (82% and 87%), as shown in Figure 6G and Table S3. [...] Additionally, 2,11-disubstituted derivatives 20m20t and 1,2,11-trisubstitued derivatives 16l were identified as the most active 5-HT2CR and 5-HT2AR dual agonists with EC50 ranging from 2.3 to 31 nM, and 6.3 to 83 nM, respectively, but showing low 5-HT2B potency, which may have the therapeutic potential for anxiety, obsessive−compulsive, and substance use disorders. CN 115108986A 27 September 2022 Aporphine derivative and preparation method and application thereof https://patents.google.com/patent/CN115108986A/en Suzhou University Shanghai Tech University Ye N, Shui W, Qin W, Zhang B, Jiang G It is the 11-methoxy derivative of asimilobine. Whereas asimilobine is a selective, lower-potency, high-efficacy partial agonist of the serotonin 5-HT2C receptor, Zhang B, Zhao S, Yang D, Wu Y, Xin Y, Cao H, Huang XP, Cai X, Sun W, Ye N, Xu Y, Peng Y, Zhao S, Liu ZJ, Zhong G, Wang MW, Shui W February 2020 A Novel G Protein-Biased and Subtype-Selective Agonist for a G Protein-Coupled Receptor Discovered from Screening Herbal Extracts ACS Central Science 6 2 213–225 10.1021/acscentsci.9b01125 free 7047268 32123739 11-methoxyasimilobine is a highly potent and selective full agonist of both the serotonin 5-HT2A and 5-HT2C receptors, with approximately 8-fold preferential activation of the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor. Its EC50 half-maximal effective concentration (Emax maximal efficacy) values were 18nM (98%) at the serotonin 5-HT2A receptor and 2.3nM (100%) at the serotonin 5-HT2C receptor. The drug is a biased agonist of the serotonin 5-HT2C receptor, favoring Gq signaling over β-arrestin recruitment by approximately 6.3-fold. It was among the most potent dual serotonin 5-HT2A and 5-HT2C receptor agonists of a large series of assessed noraporphines. Besides the serotonin 5-HTA and 5-HT2C receptors, the drug also showed weak agonism of the serotonin 5-HT2B receptor, but only at very high concentrations (EC50 half-maximal effective concentration = >10,000nM). It showed little activity at a selection of other serotonin receptors. The chemical synthesis of 11-methoxyasimilobine has been described. A variety of analogues of the drug with similar activity have also been described. 11-Methoxyasimilobine was described in the scientific literature by Wangzhi Qin and colleagues in 2025. It had previously been patented in 2022. There is interest in 11-methoxyasimilobine and related compounds for potential medical use, such as treatment of anxiety, obsessive–compulsive disorder (OCD), and substance use disorders. See also Noraporphine Asimilobine 11-Chloroasimilobine 2-Hydroxy-11-(2-methylallyl)oxynoraporphine References Category:5-HT2A agonists Category:5-HT2C agonists Category:Biased ligands Category:Noraporphines Category:Methoxy compounds