Synthesis and dopamine receptor pharmacological evaluations on ring C ortho halogenated 1-phenylbenzazepines. Issue 16 (15th August 2020)

• Record Type: Journal Article
• Authors: Giri, Rajan; Namballa, Hari K.; Sarker, Ananta; Alberts, Ian; Harding, Wayne W.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 16(2020)
• Publication Date: 2020-08-15
• Subjects: Dopamine -- D1 -- D5 -- D2 -- Benzazepine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127305
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of 1-phenylbenzazepines containing bromine or chlorine substituents at the ortho position of the appended phenyl ring (2′-monosubstituted or 2′, 6′- disubstituted patterns) were synthesized and evaluated for affinity towards dopamine D1 R, D2 R and D5 R. As is typical of the 1-phenylbenzazepine scaffold, the compounds displayed selectivity towards D1 R and D5 R; analogs generally lacked affinity for D2 R. Interestingly, 2′, 6′-dichloro substituted analogs showed modest D5 R versus D1 R selectivity whereas this selectivity was reversed in compounds with a 2′-halo substitution pattern. Compound 10a was identified as a D1 R antagonist (Ki = 14 nM; IC50 = 9.4 nM).