252853-63-7

Upstream product

• 73889-19-7 tert-butyl (1-benzylpiperidin-4-yl)carbamate 
• 50541-93-0 4-amino-1-benzylpiperidine 
• 64951-37-7 ethyl (1-phenylmethyl-4-piperidyl)carbamate 
• 7006-50-0 1-benzyl-N-methylpiperidin-4-amine 
• 3680-69-1 4-chloro-1H-pyrrolo[2,3-d]pyrimidine 

Relevant academic research and scientific papers

JANUS KINASE 1 SELECTIVE INHIBITOR AND PHARMACEUTICAL USE THEREOF

Janus kinase 1 selective inhibitors and pharmaceutical use thereof are provided.

Design, synthesis and evaluation of (R)-3-(7-(methyl?7H-pyrrolo?2, 3-d]pyrimidin-4-yl)amino)-5-azaspiro?2.4]heptan-5-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor

Based on (R)-N-methyl-N-(5-azaspiro?2.4]heptan-7-yl)-7H-pyrrolo?2, 3-d]pyrimidin-4-amine as a core scaffold, we identified (R)-3-(7-(methyl?7H-pyrrolo?2, 3-d]pyrimidin-4-yl)amino)-5-azaspiro?2.4]heptan-5- yl)-3-oxopropanenitrile [(R)-6c] as a JAK1 selective inhibitor. The structural design was based on the combination of tofacitinib's 7-deazapurine and 5-azaspiro?2.4]heptan-7-amine. Compound (R)-6c exhibited an IC50 value of 8.5 nM against JAK1 with a selectivity index of 48 over JAK2. To optimize (R)-6c as a lead compound, we performed in vitro ADME, hERG, kinase profiling, and pharmacokinetic tests. Mouse and rat in vivo studies verified that (R)-6c exhibited desired efficacies in CIA and AIA models.

Pyrrolo[2,3-d]pyrimidine compounds

A compound of the formula wherein R1, R2 and R3 are as defined above, which are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.