Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy

  • Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3736-3740. doi: 10.1016/j.bmcl.2018.10.020.
Sandeep Rana  1 ,  Yogesh A Sonawane  1 ,  Margaret A Taylor  1 ,  Smitha Kizhake  1 ,  Muhammad Zahid  2 ,  Amarnath Natarajan  3
Affiliations
  • 1. Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68022, USA.
  • 2. Department of Environmental, Agricultural and Occupational Health, Omaha, NE 68022, USA.
  • 3. Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68022, USA; Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68022, USA; Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68022, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68022, USA. Electronic address: [email protected].
PMID: 30343954 DOI: 10.1016/j.bmcl.2018.10.020
Abstract

We synthesized a library of aminopyrazole analogs to systematically explore the hydrophobic pocket adjacent to the hinge region and the solvent exposed region of cyclin dependent kinases. Structure-activity relationship studies identified an optimal substitution for the hydrophobic pocket and analog 24 as a potent and selective CDK2/5 inhibitor.

Keywords
Aminopyrazole; Cyclin dependent kinase 2; Cyclin dependent kinase 5; Growth inhibition.