864775-64-4

Usage

Uses

Used in Pharmaceutical Industry:
1H-Pyrazolo[4,3-b]pyridine,5-chloro-3-Methylis used as an intermediate in the synthesis of various pharmaceutical compounds for the treatment of different diseases. Its unique structure and potential biological activity make it a valuable component in the development of new drugs.
Used in Drug Research and Development:
1H-Pyrazolo[4,3-b]pyridine,5-chloro-3-Methylis utilized in research and development efforts to explore its potential as a drug candidate. Its wide range of applications and the possibility of modifying its structure to enhance its therapeutic properties make it an attractive option for further investigation and innovation in the pharmaceutical field.

Upstream product

• 62476-56-6 3-amino-2,6-dichloropyridine 
• 910486-72-5 6-chloro-2-ethylpyridin-3-amine 
• 864775-61-1 3-methyl-1-trityl-1H-pyrazolo[4,3-b]pyridine 
• 194278-45-0 3-methyl-1H-pyrazolo[4,3-b]pyridine 
• 87674-20-2 1-(3-fluoropyridin-2-yl)ethanone 
• 864775-63-3 3-methyl-1-trityl-1H-pyrazolo[4,3-b]pyridine 4-oxide 

Relevant academic research and scientific papers

Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening

The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development of colorectal cancer. Here we describe the successful optimization of an imidazo-thiadiazole series of CDK8 inhibitors that was identified in a high-throughput screening campaign and further progressed by structure-based design. In several optimization cycles, we improved the microsomal stability, potency, and kinase selectivity. The initial imidazo-thiadiazole scaffold was replaced by a 3-methyl-1H-pyrazolo[3,4-b]-pyridine which resulted in compound 25 (MSC2530818) that displayed excellent kinase selectivity, biochemical and cellular potency, microsomal stability, and is orally bioavailable. Furthermore, we demonstrated modulation of phospho-STAT1, a pharmacodynamic biomarker of CDK8 activity, and tumor growth inhibition in an APC mutant SW620 human colorectal carcinoma xenograft model after oral administration. Compound 25 demonstrated suitable potency and selectivity to progress into preclinical in vivo efficacy and safety studies.

2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3β phosphorylation in a BT474 tumor xenograft model in mice.

INHIBITORS OF AKT ACTIVITY

Invented are novel pyridine compounds, the use of such compounds as inhibitors of PKB/AKT kinase activity and in the treatment of cancer and arthritis.