1135429-59-2

Upstream product

• 1135429-58-1 EC₀₅₄ 
• 83255-87-2 3-bromo-1-methyl-4-aminopyrazolo<3,4-d>pyrimidine 
• 214360-73-3 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)aniline 
• 151266-23-8 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine 
• 2380-63-4 4-Aminopyrazolo<3,4-d>pyrimidin 
• 862729-12-2 3-iodo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine 

Downstream Products

• 1135429-60-5 EC₀₅₆ 
• 1135429-61-6 EC₀₅₇ 
• 1221743-62-9 1-(4-(4-amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea 

Relevant academic research and scientific papers

HETEROARYL COMPOUNDS AS TYPE II IRAK INHIBITORS AND USES HEREOF

The present invention relates to compounds of Formula (I) and pharmaceutically acceptable compositions thereof, useful as IRAK inhibitors.

Identification of 5-(2,3-Dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model

We herein report the structural optimization and structure-activity relationship studies of 5-(2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as a new class of receptor-interacting protein kinase 1 (RIPK1) inhibitors. Among all obtained RIPK1 inhibitors, 1-(5-{4-amino-7-ethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2,3-dihydro-1H-indol-1-yl)-2-[3-(trifluoromethoxy)phenyl]ethan-1-one (22b) is the most active one. This compound potently inhibited RIPK1 with a binding affinity (KD) of 0.004 μM and an enzymatic IC50 value of 0.011 μM and also showed good kinase selectivity. It could efficiently protect cells from necroptosis and attenuate the necrotic cell death of vascular endothelial cells induced by tumor cells both in vitro and in vivo. Importantly, compound 22b exhibited excellent antimetastasis activity in the experimental B16 melanoma lung metastasis model. It also displayed favorable pharmacokinetic properties. Collectively, 22b could be a promising agent for preventing tumor metastasis.

FUSED RING HETEROARYL KINASE INHIBITORS

Provided herein are fused ring heteroaryl compounds useful in a variety of methods, including reducing the activity of certain kinases and treating certain disease states.

A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL

The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed inhibitors identified an active pyrazolo-pyrimidine scaffold that was iteratively modified and screened against a collective of GroEL nucleotide pocket variants to identify a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase activity and protein folding by the GroEL mutant, I493C, involving a side chain positioned near the base of ATP. This orthogonal pair will enable in vitro studies of the action of ATP in triggering activation of GroEL-mediated protein folding and might enable further studies of GroEL action in vivo. The approach originated for studying kinases by Shokat and his colleagues may thus also be used to study large macromolecular machines.