The discovery of AZD5597, a potent imidazole pyrimidine amide CDK inhibitor suitable for intravenous dosing

  • Bioorg Med Chem Lett. 2008 Dec 15;18(24):6369-73. doi: 10.1016/j.bmcl.2008.10.102.
Clifford D Jones  1 ,  David M Andrews ,  Andrew J Barker ,  Kevin Blades ,  Paula Daunt ,  Simon East ,  Catherine Geh ,  Mark A Graham ,  Keith M Johnson ,  Sarah A Loddick ,  Heather M McFarland ,  Alexandra McGregor ,  Louise Moss ,  David A Rudge ,  Peter B Simpson ,  Michael L Swain ,  Kin Y Tam ,  Julie A Tucker ,  Mike Walker
Affiliations
  • 1. Cancer and Infection Research, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. [email protected]
PMID: 18996007 DOI: 10.1016/j.bmcl.2008.10.102
Abstract

The development of a novel series of imidazole pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of Cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modification of lipophilicity and amine basicity. A candidate with disease model activity in human Cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (i.v.) dosing was selected for further development as AZD5597.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50914
    AZD5597
    98.09%, CDK Inhibitor
    target: CDK
    Research Areas: Cancer