Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines

Bioorg Med Chem. 2007 Nov 1;15(21):6782-95. doi: 10.1016/j.bmc.2007.08.005. Epub 2007 Aug 10.

Abstract

In the present investigation, two series of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines (2a-l) and thieno[2,3-b]pyridines (3a-l) were designed as analogs of BL 11282 (1). The in vitro glucose dependent insulinotropic activity of all the test compounds was evaluated using RIN5F cell based assay and all the test compounds showed glucose and concentration dependent insulin secretion. The in vivo antidiabetic activities of most potent compounds from each series (2c and 3c) were assessed in C57BL/6J mice. Compounds 2c and 3c showed dose dependent insulin secretion and significant glucose reduction in vivo. In general, compounds 2c and 3c were found to be equipotent at all the three different doses selected and with respect to BL 11282, both the test compounds were found to be more potent, at all the time points.

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin Secretion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Pyridines