Design and synthesis of novel 2-methyl-4,5-substitutedbenzo[f]-3,3a,4,5-tetrahydro-pyrazolo[1,5-d][1,4]oxazepin-8(7H)-one derivatives as telomerase inhibitors

Bioorg Med Chem Lett. 2013 Feb 1;23(3):720-3. doi: 10.1016/j.bmcl.2012.11.101. Epub 2012 Dec 3.

Abstract

Eight novel 4,5-tetrahydropyrazolo[1,5-d][1,4]oxazepine derivatives have been synthesized and purified to be screened for anticancer activity. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC(50) value at 0.78 ± 0.22 μM. Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Crystallography, X-Ray
  • Drug Design*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Oxazepines / chemistry
  • Pyrazoles / chemistry
  • Telomerase / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Oxazepines
  • Pyrazoles
  • Telomerase