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

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127305. doi: 10.1016/j.bmcl.2020.127305. Epub 2020 Jun 4.

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 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 (Ki = 14 nM; IC50 = 9.4 nM).

Keywords: Benzazepine; D1; D2; D5; Dopamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzazepines / chemical synthesis
  • Benzazepines / chemistry
  • Benzazepines / pharmacology*
  • Dopamine Antagonists / chemical synthesis
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Halogenation
  • Molecular Structure
  • Receptors, Dopamine D1 / agonists*
  • Structure-Activity Relationship

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Receptors, Dopamine D1