Synthesis, crystal structure and biological activity of novel analogues of tricyclic drugs

Bioorg Med Chem Lett. 2020 Nov 1;30(21):127493. doi: 10.1016/j.bmcl.2020.127493. Epub 2020 Aug 13.

Abstract

A series of fourteen novel, eight-membered lactam- and dilactam-based analogues of tricyclic drugs were obtained in a simple one-pot procedure. Crystal structures of two compounds were determined by single-crystal X-ray diffraction analysis and their selected structural features were discussed and compared with those of imipramine and dibenzepine. Affinity of developed molecules for histamine receptor H1, serotonin receptors 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, serotonin transporter (SERT) and dopamine receptor D2 was determined. The commercial drug dibenzepine was also checked on these molecular targets, as its mechanism of action is largely unknown. Two derivatives of 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one (7,8) and two of dibenzo[b,f]azocin-6(5H)-one (9,10) were found to be active toward the H1 receptor in sub-micromolar concentrations.

Keywords: 5 HT receptors; D(2) receptor; Dibenzepine; H(1) receptor; SERT inhibitors; Tricyclic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents, Tricyclic / chemical synthesis
  • Antidepressive Agents, Tricyclic / chemistry
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Humans
  • Lactams / chemical synthesis
  • Lactams / chemistry
  • Lactams / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Receptors, Dopamine / metabolism*
  • Receptors, Histamine / metabolism*
  • Receptors, Serotonin / metabolism*
  • Structure-Activity Relationship

Substances

  • Antidepressive Agents, Tricyclic
  • Lactams
  • Receptors, Dopamine
  • Receptors, Histamine
  • Receptors, Serotonin