1616689-72-5Relevant academic research and scientific papers
Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors
Ramachandran, Sreekanth A.,Jadhavar, Pradeep S.,Miglani, Sandeep K.,Singh, Manvendra P.,Kalane, Deepak P.,Agarwal, Anil K.,Sathe, Balaji D.,Mukherjee, Kakoli,Gupta, Ashu,Haldar, Srijan,Raja, Mohd,Singh, Siddhartha,Pham, Son M.,Chakravarty, Sarvajit,Quinn, Kevin,Belmar, Sebastian,Alfaro, Ivan E.,Higgs, Christopher,Bernales, Sebastian,Herrera, Francisco J.,Rai, Roopa
, p. 2153 - 2160 (2017)
Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice.
AZAINDOLE DERIVATIVES AS MULTI KINASE INHIBITORS
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Page/Page column 66, (2014/07/21)
The present invention relates to compounds of the following formula (I) and/or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.
