| Literature DB >> 18996007 |
Clifford D Jones1, 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.
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.Entities:
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Year: 2008 PMID： 18996007 DOI： 10.1016/j.bmcl.2008.10.102
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823