70608-99-0

Upstream product

• 20570-96-1 benzylhydrazine dihydrochloride 
• 762-21-0 acetylenedicarboxylic acid diethyl ester 
• 1073-62-7 N-benzylhydrazine hydrochloride 
• 88330-76-1 diethyl oxalacetate sodium salt 

Relevant academic research and scientific papers

INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE

Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1 -mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.

HETEROCYCLIC COMPOUND

The present invention provides a heterocyclic compound having an RIP1 kinase inhibitory action, which is useful for the prophylaxis or treatment of Gaucher's disease, Niemann-Pick disease, inflammatory bowel disease, multiple sclerosis, chronic kidney disease, acute kidney injury, acute hepatic failure, autoimmune hepatitis, hepatitis B, hepatitis C, alcohol steatohepatitis, non-alcohol steatohepatitis and the like. The present invention relates to a compound represented by the following formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H -pyrazolo[3,4- c] pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships

We report the discovery of 7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine derivatives as a novel class of receptor interacting protein 1 (RIP1) kinase inhibitors. On the basis of the overlay study between HTS hit 10 and GSK2982772 (6) in RIP1 kinase, we designed and synthesized a novel class of RIP1 kinase inhibitor 11 possessing moderate RIP1 kinase inhibitory activity and P-gp mediated efflux. The optimization of the core structure and the exploration of appropriate substituents utilizing SBDD approach led to the discovery of 22, a highly potent, orally available, and brain-penetrating RIP1 kinase inhibitor with excellent PK profiles. Compound 22 significantly suppressed necroptotic cell death both in mouse and human cells. Oral administration of 22 (10 mg/kg, bid) attenuated disease progression in the mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Moreover, analysis of structure-kinetic relationship (SKR) for our novel chemical series was also discussed.

SGC STIMULATORS

The present patent application discloses at least the compounds according to Formula I' shown below, or pharmaceutically acceptable salts thereof, Formula (I) wherein ring D, ring A, ring E, JB, n, JD, J, X, Z, Z1, RC

SUBSTITUTED BENZYLPYRAZOLES

Compounds of formula (I) and their use as pharmaceutical.

SUBSTITUTED BENZYLPYRAZOLES

Compounds of formula (I) and their use as pharmaceutical.