Synthesis and dopamine receptor pharmacological evaluations on ring C ortho halogenated 1-phenylbenzazepines

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Giri, Rajan^1,2  Namballa, Hari K.¹  Sarker, Ananta¹  Alberts, Ian³  Harding, Wayne W.^1,2,4 

[1] CUNY Hunter Coll, Dept Chem, 695 Pk Ave, New York, NY 10065 USA

[2] CUNY, Program Chem, Grad Ctr, 365 5th Ave, New York, NY 10016 USA

[3] LaGuardia Community Coll, Dept Chem, 31-10 Thompson Ave, Lic, NY 11104 USA

[4] CUNY, Program Biochem, Grad Ctr, 365 5th Ave, New York, NY 10016 USA

关键词: Dopamine;    D1;    D5;    D2;    Benzazepine;   

DOI  :  10.1016/j.bmcl.2020.127305

来源: Elsevier

【 摘 要 】

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 D1R, D2R and D5R. As is typical of the 1-phenylbenzazepine scaffold, the compounds displayed selectivity towards D1R and D5R; analogs generally lacked affinity for D2R. Interestingly, 2',6'-dichloro substituted analogs showed modest D5R versus D1R selectivity whereas this selectivity was reversed in compounds with a 2'-halo substitution pattern. Compound 10a was identified as a D1R antagonist (K-1 = 14 nM; IC50 = 9.4 nM).

【 授权许可】

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