Synthesis and evaluation of novel triazoles and mannich bases functionalized 1,4-dihydropyridine as angiotensin converting enzyme (ACE) inhibitors

Bioorg Med Chem. 2014 Nov 1;22(21):5824-30. doi: 10.1016/j.bmc.2014.09.027. Epub 2014 Sep 19.

Abstract

A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM.

Keywords: 1,4-Dihydropyridine; Angiotensin converting enzyme; Inhibitors; Mannich bases; Triazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*
  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dihydropyridines / chemistry
  • Enzyme Activation / drug effects
  • HEK293 Cells
  • Humans
  • Mannich Bases / chemical synthesis
  • Mannich Bases / chemistry*
  • Mannich Bases / pharmacology
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Binding
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Dihydropyridines
  • Mannich Bases
  • Triazoles
  • 1,4-dihydropyridine
  • Peptidyl-Dipeptidase A