Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors

作者：Belanger David B^*; Williams Michael J; Curran Patrick J; Mandal Amit K; Meng Zhaoyang; Rainka Matthew P; Yu Tao; Shih Neng Yang; Siddiqui M Arshad; Liu Ming; Tevar Seema; Lee Suining; Liang Lianzhu; Gray Kimberly; Yaremko Bohdan; Jones Jennifer; Smith Elizabeth B; Prelusky Dan B; Basso Andrea D

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(22): 6739-6743.

DOI：10.1016/j.bmcl.2010.08.140

• Aurora kinase inhibitors
• Imidazo[1,2-a]pyrazine
• Oral bioavailability
• Tumor xenograft mouse model

We report a series of potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Optimization of the solvent accessible 8-position led to improvements in both oral bioavailability and off-target kinase inhibition. Compound 25 demonstrates anti-tumor activity in an A2780 ovarian tumor xenograft model.

• 出版日期2010-11-15