1254161-77-7

Upstream product

• 15801-69-1 4-bromo-1,3,5-trimethylpyrazole 
• 50533-97-6 dimethyl-piperidin-4-yl-amine 
• 1254163-25-1 6-(4-dimethylamino-piperidin-1-yl)-pyridin-2,3-diyl-diamine 
• 1254163-26-2 [1-(3H-imidazo[4,5-b]pyridin-5-yl)piperidin-4-yl]dimethylamine 
• 1254163-62-6 4-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzoic acid methyl ester 
• 1254163-31-9 [1-(3-dimethylaminomethyl-3H-imidazo[4,5-b]pyridin-5-yl)-piperidin-4-yl]-dimethyl-amine 
• 1254163-24-0 6-(4-dimethylamino-piperidin-1-yl)-3-nitro-pyridin-2-yl-amine 
• 27048-04-0 2-amino-6-chloro-3-nitropyridine 

Relevant academic research and scientific papers

Fragment-based discovery of 7-azabenzimidazoles as potent, highly selective, and orally active CDK4/6 inhibitors

Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model.

IMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF CYCLIN DEPENDENT KINASES

The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N+-O- or CR3; Y is N, N+-O- or CR3a; R1 and R2 are independently selected from hydrogen and various substituents as defined in the claims; or R1 and R2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R3 is selected from hydrogen and various substituents; and R3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.