Substituted 3-benzazepine

A substituted 3-benzazepine, or simply 3-benzazepine, is a derivative of 3-benzazepine.[2][3][4] They are cyclized phenethylamines and are closely related to the tetrahydroisoquinolines.[2][3] In addition, they are analogous to the cyclized tryptamine ibogalogs and their β-carboline relatives.[5][6]

3-Benzazepines are known to act as monoamine receptor modulators, including as dopamine D1-like receptor agonists, dopamine D1 receptor antagonists, and serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonists, among other activities.[2][3][4][7][8][9][10] 3-Benzazepines acting as serotonin 5-HT2 receptor agonists generally show varying degrees of preferential activity at the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor, with occasional exceptions.[9] One 3-benzazepine, the non-selective serotonin 5-HT2 receptor agonist and previously marketed anorectic lorcaserin (Belviq), is known to produce psychedelic effects at supratherapeutic doses.[11]

List of 3-benzazepines

Structure Name Action Chemical name Ref
3-Benzazepine N/A 3H-3-benzazepine
SKF-39315 D1-like agonist 2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
Lorcaserin 5-HT2 agonist (1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
7-Chlorolorcaserin 5-HT2 agonist (1R)-7,8-dichloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
SCHEMBL5334361 5-HT2 agonist 7-[(3-methoxyphenoxy)methyl]-2,3,4,5-tetrahydro-1H-3-benzazepine
SKF-38393 D1-like agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
SKF-81297 D1-like agonist (1R)-6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
Fenoldopam D1-like agonist 6-chloro-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
SCH-23390 D1 antagonist (5R)-8-chloro-3-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol
SKF-83959 D1-like agonist 6-chloro-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
Trepipam (SCH-12679) D1-like agonist 7,8-dimethoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
SKF-77434 D1-like agonist (1R)-1-phenyl-3-(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
SKF-82958 D1-like agonist (1R)-6-chloro-1-phenyl-3-(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
6-Br-APB D1-like agonist (1R)-6-bromo-1-phenyl-3-(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
Odapipam (NNC 01-0756) D1 antagonist (5S)-8-chloro-5-(2,3-dihydro-1-benzofuran-7-yl)-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol
Berupipam (NNC 22-0010) D1 antagonist (5S)-5-(5-bromo-2,3-dihydro-1-benzofuran-7-yl)-8-chloro-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol
NNC 01-0687 (ADX-10061, CEE-03-310) D1 antagonist (5S)-5-(2,3-dihydro-1-benzofuran-7-yl)-3-methyl-8-nitro-1,2,4,5-tetrahydro-3-benzazepin-7-ol
GSK-189254 H3 antagonist 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methylpyridine-3-carboxamide
Anilopam (PR 786-723) Opioid 4-[2-(7-methoxy-4-methyl-1,2,4,5-tetrahydro-3-benzazepin-3-yl)ethyl]aniline

See also

References

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  2. ^ a b c Weinstock J, Hieble JP, Wilson JW (1985). "The chemistry and pharmacology of 3-benzazepine derivatives". Drugs Future. 10: 645–696.
  3. ^ a b c Kawase M, Saito S, Motohashi N (April 2000). "Chemistry and biological activity of new 3-benzazepines". Int J Antimicrob Agents. 14 (3): 193–201. doi:10.1016/s0924-8579(99)00155-7. PMID 10773487.
  4. ^ a b Shah, J. H., Hindupur, R. M., & N Pati, H. (2015). Pharmacological and biological activities of benzazepines: An overview. Current Bioactive Compounds, 11(3), 170–188. https://doi.org/10.2174/1573407211666150910202200
  5. ^ Iyer, R. N., Favela, D., Zhang, G., & Olson, D. E. (2021). The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. Natural Product Reports, 38(2), 307–329. https://doi.org/10.1039/D0NP00033G
  6. ^ Shulgin AT (1982). "Chemistry of Psychotomimetics". In Hoffmeister F, Stille G (eds.). Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs. Handbook of Experimental Pharmacology. Vol. 55 / 3. Berlin: Springer Berlin Heidelberg. pp. 3–29. doi:10.1007/978-3-642-67770-0_1. ISBN 978-3-642-67772-4. OCLC 8130916.
  7. ^ Iorio LC, Barnett A, Billard W, Gold EH (1986). "Benzazepines: structure-activity relationships between D1 receptor blockade and selected pharmacological effects". Adv Exp Med Biol. 204: 1–14. doi:10.1007/978-1-4684-5191-7_1. PMID 2947422.
  8. ^ Lee J, Jung ME, Lee J (November 2010). "5-HT2C receptor modulators: a patent survey". Expert Opin Ther Pat. 20 (11): 1429–1455. doi:10.1517/13543776.2010.518956. PMID 20849206.
  9. ^ a b Smith, Brian M.; Smith, Jeffrey M.; Tsai, James H.; Schultz, Jeffrey A.; Gilson, Charles A.; Estrada, Scott A.; Chen, Rita R.; Park, Douglas M.; Prieto, Emily B.; Gallardo, Charlemagne S.; Sengupta, Dipanjan; Thomsen, William J.; Saldana, Hazel R.; Whelan, Kevin T.; Menzaghi, Frederique; Webb, Robert R.; Beeley, Nigel R.A. (2005). "Discovery and SAR of new benzazepines as potent and selective 5-HT2C receptor agonists for the treatment of obesity". Bioorganic & Medicinal Chemistry Letters. 15 (5): 1467–1470. doi:10.1016/j.bmcl.2004.12.080. Retrieved 13 October 2025.
  10. ^ Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Dosa PI, Covel JA, Ren A, Webb RR, Beeley NR, Martin M, Morgan M, Espitia S, Saldana HR, Bjenning C, Whelan KT, Grottick AJ, Menzaghi F, Thomsen WJ (January 2008). "Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity". J Med Chem. 51 (2): 305–313. doi:10.1021/jm0709034. PMID 18095642.
  11. ^ Collins GT, Gerak LR, France CP (November 2018). "The behavioral pharmacology and therapeutic potential of lorcaserin for substance use disorders". Neuropharmacology. 142: 63–71. doi:10.1016/j.neuropharm.2017.12.023. PMC 5997497. PMID 29246856. [...] several lines of evidence suggest that lorcaserin also has actions at 5-HT2A receptors. First, in vitro functional studies suggest that lorcaserin is only modestly (~19-fold) selective for 5-HT2C over 5-HT2A receptors in vitro (Thomsen et al., 2008; also see Table 1), raising the possibility that the doses required to decrease intravenous drug self-administration are large enough to bind to and possibly exert effects at 5-HT2A receptors. Indeed, when evaluated in a sample of recreational polydrug users, doses only slightly larger (20-60 mg) than the maximally approved dose of 10 mg (administered twice daily [BID]) produced feelings of "high" and "bad effects", as well as perceptual changes that were described by a subset of subjects as "hallucination" and/or feeling "detached" and "spaced out" (Shram et al., 2011). Dose-dependent increases in other adverse effects (e.g., nausea, headache, dizziness, euphoric mood, etc.) were also noted, with most subjects (70-100%) reporting at least one adverse effect after receiving larger doses of lorcaserin (Shram et al., 2011).
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