2. Academic Validation
  3. Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy

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

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: anatarajan@unmc.edu.
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.

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