CHEM-X-INFINITY AND ORIBASE PHARMA RELEASE A KINASE FOCUSED LIBRARY
Small heterocycles are often the starting point for many medicinal chemistry projects, especially nitrogen-containing ones for kinase inhibition for which the existence of privileged scaffolds was demonstrated. This was confirmed in 2013 with the registration of seven small molecules kinase inhibitors including ponatinib, a pan-BCR-ABL, VEGFR2, FGFR1, PDGFR and LYN kinase inhibitor for chronic myelogenous leukemia and acute lymphoblastic leukemia. Ponatinib contains the imidazo[1,2-b]pyridazine scaffold. Other nitrogen containing small heterocycles that could be valuable in kinase inhibition are poorly represented in commercial collections due to synthetic difficulties. To have access to some of those challenging molecules, we decided to collaborate with Oribase Pharma which demonstrated an expertise in heterocyclic chemistry for the design of new generations of kinase targeted compounds. Ten original molecules were designed, synthesized and produced on our automated platform to obtain the library of more than 600 final molecules. The six represented scaffolds are pyrazolo-[1,5-a]-pyrimidine, thieno-[3,2-b]-pyridine, pyrrolo-[1,2-a]-pyrimidine, imidazo-[1,2-a]-pyrimidine, furo-[2,3-b]-pyridine and quinoline-6-carboxamide.
Specific applications could be CDK, CHK, B-Raf, AMPK, c-MET, VEGF, Tie, EGFR and Src kinase inhibition. The small molecules that strictly respect the Lipinski rules could also be used for GABA-A receptor, acetyl coenzyme-A carboxylase, cannabinoid receptor and gonadotropin-releasing hormone inhibition.
Details and scientific references can be found in the ChemHit3 library brochure.
Feel free to request a login password to have access to the structures.