1207261-66-2

Upstream product

• 72081-99-3 (Z)-N’-hydroxyquinoline-2-carboximidamide 
• 926199-06-6 C₁₄H₁₈N₂O₄ 
• 1436-43-7 quinoline-2-carbonitrile 

Relevant academic research and scientific papers

Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl] piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors

The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway.

1,2,4-OXADIAZOLE SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS SMO ANTAGONISTS

The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts, stereoisomers or tautomers thereof which are inhibitors of the Sonic Hedgehog pathway, in particular Smo antagonists. Thus the compounds of this invention are useful for the treatment of diseases associated with abnormal hedgehog pathway activation, including cancer, for example basal cell carcinoma, medulloblastoma, prostate, pancreatic, breast, colon, bone and small cell lung cancers, and cancers of the upper GI tract.