1129540-59-5Relevant academic research and scientific papers
Hit-to-Lead Optimization of Benzoxazepinoindazoles As Human African Trypanosomiasis Therapeutics
Klug, Dana M.,Tschiegg, Laura,Diaz, Rosario,Rojas-Barros, Domingo,Perez-Moreno, Guiomar,Ceballos, Gloria,García-Hernández, Raquel,Martinez-Martinez, Maria Santos,Manzano, Pilar,Ruiz, Luis Miguel,Caffrey, Conor R.,Gamarro, Francisco,Pacanowska, Dolores Gonzalez,Ferrins, Lori,Navarro, Miguel,Pollastri, Michael P.
, p. 2527 - 2546 (2019/11/28)
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by infection with either of two subspecies of the parasite Trypanosoma brucei. Due to a lack of economic incentive to develop new drugs, current treatments have severe limitations in terms of safety, efficacy, and ease of administration. In an effort to develop new HAT therapeutics, we report the structure-activity relationships around T. brucei for a series of benzoxazepinoindazoles previously identified through a high-throughput screen of human kinase inhibitors, and the subsequent in vivo experiments for HAT. We identified compound 18, which showed an improved kinase selectivity profile and acceptable pharmacokinetic parameters, as a promising lead. Although treatment with 18 cured 60% of mice in a systemic model of HAT, the compound was unable to clear parasitemia in a CNS model of the disease. We also report the results of cross-screening these compounds against T. cruzi, L. donovani, and S. mansoni.
SUBSTITUTED PYRIMIDINYL-AMINES AS PROTEIN KINASE INHIBITORS
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Page/Page column 46; 47, (2009/04/25)
The present invention provides novel substituted pyrimidinyl-amines that are useful as inhibitors of protein kinases, especially c-Jun N-terminal kinases (JNK) and pharmaceutical compositions thereof and methods of using the same for treating conditions responsive to the inhibition of the JNK pathway.
