Discovery of novel isothiazole inhibitors of the TrkA kinase: structure–activity relationship, computer modeling, optimization, and identification of highly potent …

…, SL Snow, TG Gant, M Mangiaracina, HA Coffey…

文献索引：Lippa, Blaise; Morris, Joel; Corbett, Matthew; Kwan, Tricia A.; Noe, Mark C.; Snow, Sheri L.; Gant, Thomas G.; Mangiaracina, Melchiorra; Coffey, Heather A.; Foster, Barbara; Knauth, Elisabeth A.; Wessel, Matthew D. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 13 p. 3444 - 3448

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被引用次数: 38

摘要

The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series. Aminoheterocycles are found to be good urea surrogates, whereas bicyclic substituents on the C3 thio group ...