- 2-anilino-4-aryl-8H-purine derivatives as inhibitors of PDK1.
2-anilino-4-aryl-8H-purine derivatives as inhibitors of PDK1.
Bioorganic & medicinal chemistry letters (2012-03-23)
Stéphanie Blanchard, Chang Kai Soh, Chai Ping Lee, Anders Poulsen, Zahid Bonday, Kay Lin Goh, Kee Chuan Goh, Miah Kiat Goh, Mohammed Khalid Pasha, Haishan Wang, Meredith Williams, Jeanette M Wood, Kantharaj Ethirajulu, Brian W Dymock
PMID22437109
摘要
A series of 2-anilino substituted 4-aryl-8H-purines were prepared as potent inhibitors of PDK1, a serine-threonine kinase thought to play a role in the PI3K/Akt signaling pathway, a key mediator of cancer cell growth, survival and tumorigenesis. The synthesis, SAR and ADME properties of this series of compounds are discussed culminating in the discovery of compound 6 which possessed sub-micromolar cell proliferation activity and 65% oral bioavailability in mice.
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