859027-17-1Relevant articles and documents
ISOQUINOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES
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Paragraph 0224; 0225; 0256; 0327, (2022/02/06)
The present invention discloses compounds according to Formula (I) wherein R1, R2, R3, L1, L2, and L3 are as defined herein. The present invention relates to compounds inhibiting discoidin domain receptors (DDRs), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of fibrotic diseases, inflammatory diseases, respiratory diseases, autoimmune diseases, metabolic diseases, cardiovascular diseases, and/or proliferative diseases by administering a compound of the invention.
Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform
Desai, Bimbisar,Dixon, Karen,Farrant, Elizabeth,Feng, Qixing,Gibson, Karl R.,Van Hoorn, Willem P.,Mills, James,Morgan, Trevor,Parry, David M.,Ramjee, Manoj K.,Selway, Christopher N.,Tarver, Gary J.,Whitlock, Gavin,Wright, Adrian G.
, p. 3033 - 3047 (2013/05/22)
Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure-activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC50 > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.