Optimization of a dihydropyrrolopyrazole series of transforming growth factor-β type I receptor kinase domain inhibitors: Discovery of an orally bioavailable …

H Li, WT McMillen, CR Heap, DJ McCann…

文献索引：Li, Hong-Yu; McMillen, William T.; Heap, Charles R.; McCann, Denis J.; Yan, Lei; Campbell, Robert M.; Mundla, Sreenivasa R.; King, Chi-Hsin R.; Dierks, Elizabeth A.; Anderson, Bryan D.; Britt, Karen S.; Huss, Karen L.; Voss, Matthew D.; Wang, Yan; Clawson, David K.; Yingling, Jonathan M.; Sawyer, J. Scott Journal of Medicinal Chemistry, 2008 , vol. 51, # 7 p. 2302 - 2306

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被引用次数: 43

摘要

In our continuing effort to expand the SAR of the quinoline domain of dihydropyrrolopyrazole series, we have discovered compound 15d, which demonstrated the antitumor efficacy with oral bioavailability. This effort also demonstrated that the PK/PD in vivo target inhibition paradigm is an effective approach to assess potential for antitumor efficacy. The dihydropyrrolopyrazole inhibitor 15d (LY2109761) is representative of a novel series of ...