1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline

vanc 6 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline.svg skin-invert-image 250px Serotonin receptor modulator; Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonin 5-HT2C receptor agonist None 528525-37-3 4376990 3579186 5207529 "Compound 106"; 6-Chloro-1-(2,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline; 1-(2,4,5-OMePh)-6-Cl-THβC 6-chloro-1-(2,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole 20 21 1 2 3 COC1=CC(=C(C=C1C2C3=C(CCN2)C4=C(N3)C=CC(=C4)Cl)OC)OC 1S/C20H21ClN2O3/c1-24-16-10-18(26-3)17(25-2)9-14(16)19-20-12(6-7-22-19)13-8-11(21)4-5-15(13)23-20/h4-5,8-10,19,22-23H,6-7H2,1-3H3 RJHMAXLLXKUOBW-UHFFFAOYSA-N 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline, also known as 6-chloro-1-(2,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline, is a serotonin receptor modulator of the β-carboline family. Orr MJ, Cao AB, Wang CT, Gaisin A, Csakai A, Friswold AP, Meltzer HY, McCorvy JD, Scheidt KA April 2022 Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products ACS Medicinal Chemistry Letters 13 4 648–657 10.1021/acsmedchemlett.1c00694 9014500 35450369 It is a ring-substituted derivative of the β-carboline tryptoline (THβC) and a simplified analogue of the heteroyohimbine alkaloid alstonine. Pharmacology Pharmacodynamics 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline acts as a highly potent full agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. Its EC50 half-maximal effective concentration (Emax maximal efficacy) values were 1.7nM (98.4%) at the serotonin 5-HT2A receptor, 0.50nM (97.5%) at the serotonin 5-HT2B receptor, and 0.58nM (96.7%) at the serotonin 5-HT2C receptor. The drug was one of the most potent serotonin 5-HT2A receptor agonists of a large series of assessed tryptoline derivatives. 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline's potent serotonin 5-HT2 receptor agonism is in notable contrast to other simpler β-carbolines like harmine and harmaline, which have been found to be inactive as serotonin 5-HT2A receptor agonists even at very high concentrations. Grella B, Teitler M, Smith C, Herrick-Davis K, Glennon RA December 2003 Binding of beta-carbolines at 5-HT(2) serotonin receptors Bioorganic & Medicinal Chemistry Letters 13 24 4421–4425 10.1016/j.bmcl.2003.09.027 14643338 Rabin RA, Regina M, Doat M, Winter JC 5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens Pharmacol Biochem Behav 72 1-2 29–37 May 2002 11900766 10.1016/s0091-3057(01)00720-1 Rolquin Jeremy D Examining Ayahuasca Constituents at 5-HT2A Receptors in Search of Antidepressant Action VCU Scholars Compass 3 May 2022 https://scholarscompass.vcu.edu/etd/6884/ 7 April 2026 Similarly, tryptoline itself shows very low affinity for serotonin 5-HT2 receptors. Bojarski AJ, Cegła MT, Charakchieva-Minol S, Mokrosz MJ, Maćkowiak M, Misztal S, Mokrosz JL April 1993 Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines Die Pharmazie 48 4 289–294 8321880 https://www.researchgate.net/profile/Marek-Cegla-2/publication/14877180_Structure-activity_relationship_studies_of_CNS_agents_Part_9_5-HT1A_and_5-HT2_receptor_affinity_of_some_2-_and_3-substituted_1234-tetrahydro-b-carbolines/links/5538ce710cf2239f4e79ba51/Structure-activity-relationship-studies-of-CNS-agents-Part-9-5-HT1A-and-5-HT2-receptor-affinity-of-some-2-and-3-substituted-1-2-3-4-tetrahydro-b-carbolines.pdf 2026-04-04 2026-04-04 https://web.archive.org/web/20260404220751/https://www.researchgate.net/profile/Marek-Cegla-2/publication/14877180_Structure-activity_relationship_studies_of_CNS_agents_Part_9_5-HT1A_and_5-HT2_receptor_affinity_of_some_2-_and_3-substituted_1234-tetrahydro-b-carbolines/links/5538ce710cf2239f4e79ba51/Structure-activity-relationship-studies-of-CNS-agents-Part-9-5-HT1A-and-5-HT2-receptor-affinity-of-some-2-and-3-substituted-1-2-3-4-tetrahydro-b-carbolines.pdf bot: unknown Taylor EW, Nikam S, Weck B, Martin A, Nelson D October 1987 Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites Life Sciences 41 16 1961–1969 10.1016/0024-3205(87)90749-1 3657392 Cascio CS, Kellar KJ November 1982 Tetrahydro-beta-carbolines: affinities for tryptamine and serotonergic binding sites Neuropharmacology 21 11 1219–1221 10.1016/0028-3908(82)90185-x 7177348 In addition to the serotonin 5-HT2 receptors, 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline shows variable but mostly high affinity for most other serotonin receptors (Ki = 2.50–1,493nM). Interactions at other receptors have also been reported. Chemistry Synthesis The chemical synthesis of 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline has been described. Analogues A large number of analogues of 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline have been described. History 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline was first described in the scientific literature by Meghan J. Orr and colleagues in 2022. See also Substituted β-carboline List of miscellaneous serotonin 5-HT2A receptor agonists 1-Ethyl-6-hydroxytryptoline Pinoline NU-1223 LY-266,097 LY-272,015 Fenharmane References Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Chloroarenes Category:Trimethoxyphenyl compounds Category:Serotonin receptor modulators Category:Tryptolines