Substituted 3-benzazepine

Class of chemical compounds From Wikipedia, the free encyclopedia

A substituted 3-benzazepine, or simply 3-benzazepine, is a derivative of 3-benzazepine.^[2]^[1]^[3] They are cyclized phenethylamines and are closely related to the tetrahydroisoquinolines.^[2]^[1] In addition, they are analogous to the cyclized tryptamine ibogalogs and their β-carboline relatives.^[4]^[5]

SKF-81297, a dopamine D₁-like receptor agonist of the 3-benzazepine group.^[1]

3-Benzazepines are known to act as monoamine receptor modulators, including as dopamine D₁-like receptor agonists, dopamine D₁ receptor antagonists, and serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptor agonists, among other activities.^[2]^[1]^[3]^[6]^[7]^[8]^[9] 3-Benzazepines acting as serotonin 5-HT₂ receptor agonists generally show varying degrees of preferential activity at the serotonin 5-HT_2C receptor over the serotonin 5-HT_2A receptor, with occasional exceptions.^[8] 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.^[10]

List of 3-benzazepines

More information Structure, Name ...

Name	Action	Chemical name
3-Benzazepine	N/A	3H-3-benzazepine
2,3,4,5-Tetrahydro-1H-3-benzazepine	N/A	2,3,4,5-tetrahydro-1H-benzo[d]azepine
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

Related compounds

More information Structure, Name ...

Name	Action	Chemical name	Ref
PF-04479745 (PF-4479745)	5-HT₂ modulator	(9S)-2-benzyl-N,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine	^[11]
PF-04781340	5-HT₂ modulator	3-benzyl-N-methyl-6,7,8,9-tetrahydro-5H-pyrido[3,4-d]azepin-1-amine	^[12]
PF-4522654 (PF-04522654)	5-HT₂ modulator	2-[difluoro(phenyl)methyl]-N-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-amine	^[11]

References

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[2]
Weinstock J, Hieble JP, Wilson JW (1985). "The chemistry and pharmacology of 3-benzazepine derivatives". Drugs Future. 10: 645–696.
[3]
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
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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
[5]
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.
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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.
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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.
[8]
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.
[9]
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.
[10]
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).
[11]
Storer RI, Brennan PE, Brown AD, Bungay PJ, Conlon KM, Corbett MS, DePianta RP, Fish PV, Heifetz A, Ho DK, Jessiman AS, McMurray G, de Oliveira CA, Roberts LR, Root JA, Shanmugasundaram V, Shapiro MJ, Skerten M, Westbrook D, Wheeler S, Whitlock GA, Wright J (June 2014). "Multiparameter optimization in CNS drug discovery: design of pyrimido[4,5-d]azepines as potent 5-hydroxytryptamine 2C (5-HT₂C) receptor agonists with exquisite functional selectivity over 5-HT₂A and 5-HT₂B receptors". J Med Chem. 57 (12): 5258–5269. doi:10.1021/jm5003292. PMID 24878222.
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Rouquet G, Moore DE, Spain M, Allwood DM, Battilocchio C, Blakemore DC, Fish PV, Jenkinson S, Jessiman AS, Ley SV, McMurray G, Storer RI (March 2015). "Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists". ACS Med Chem Lett. 6 (3): 329–333. doi:10.1021/ml500507v. PMC 4360148. PMID 25815155.

Substituted 3-benzazepine

List of 3-benzazepines

Related compounds

See also

References

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