1419214-70-2

Upstream product

• 106447-97-6 2-amino-4-(trifluoromethyl)pyridine 
• 1419221-80-9 benzyl (R)-3-(8-amino-1-bromoimidazo[1,5-a]-pyrazin-3-yl)piperidine-1-carboxylate 
• 1419221-79-6 benzyl (3R)-3-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate 
• 1419221-78-5 benzyl (3R)-3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate 
• 586-76-5 4-Bromobenzoic acid 
• 586-75-4 4-chlorobenzoyl chloride 
• 1419221-77-4 benzyl (3R)-3-([(3-chloropyrazin-2-yl)methyl]carbamoyl)piperidine-1-carboxylate 
• 160706-62-7 (R)-1-((benzyloxy)carbonyl)piperidine-3-carboxylic acid 
• 1418307-30-8 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(4-trifluoromethyl-pyridin-2-yl)-benzamide 
• 1419214-71-3 (R)-benzyl 3-(8-amino-1-(4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate 

Downstream Products

• 1419214-33-7 (R)-4-(8-amino-3-(1-(3-methyloxetane-3-carbonyl)piperidin-3-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide 

Relevant academic research and scientific papers

Discovery of 8-Amino-imidazo[1,5-a]pyrazines as Reversible BTK Inhibitors for the Treatment of Rheumatoid Arthritis

Bruton's tyrosine kinase (BTK) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) pathway. It has become an attractive kinase target for selective B cell inhibition and for the treatment of B cell related diseases. We report a series of compounds based on 8-amino-imidazo[1,5-a]pyrazine that are potent reversible BTK inhibitors with excellent kinase selectivity. Selectivity is achieved through specific interactions of the ligand with the kinase hinge and driven by aminopyridine hydrogen bondings with Ser538 and Asp539, and by hydrophobic interaction of trifluoropyridine in the back pocket. These interactions are evident in the X-ray crystal structure of the lead compounds 1 and 3 in the complex with the BTK enzyme. Our lead compounds show desirable PK profiles and efficacy in the preclinical rat collagen induced arthritis model.

4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors

The present invention provides 6-5 membered fused pyridine ring compounds according to Formula I or pharmaceutically acceptable salts thereof. or a pharmaceutically acceptable salt thereof or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of 6-5 membered fused pyridine ring compounds in the treatment of Bruton's Tyrosine Kinase (Btk) mediated disorders.