898228-08-5

Upstream product

• 505-66-8 1,4-Diazacycloheptane 
• 856165-97-4 ethyl 6-chloro-5-cyanonicotinate 
• 52600-52-9 5-Cyano-2-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid ethyl ester 
• 64119-42-2 ethyl 6-chloro-5-cyano-2-methylnicotinate 

Relevant academic research and scientific papers

Synthesis, structure-property relationships and pharmacokinetic evaluation of ethyl 6-aminonicotinate sulfonylureas as antagonists of the P2Y12 receptor

The present paper describes the development of a new series of P2Y 12 receptor antagonists based on our previously reported piperazinyl urea series 1 (IC50 binding affinity = 0.33 μM, aq solubility 50 binding affinity = 0.042 μM, aq solubility = 90 μM, microsomal CLint (HLM) = 70 μM/min/mg). Further improvements in affinity and metabolic stability were achieved by replacing the central piperazine ring with a 3-aminoazetidine as exemplified by 3 (IC50 binding affinity = 0.0062 μM, aq solubility = 83 μM, microsomal CLint (HLM) = 28 μM/min/mg). The improved affinity observed in the in vitro binding assay also translated to the potency observed in the WPA aggregation assay (47: 19 nM and 3: 9.5 nM) and the observed in vitro ADME properties translates to the in vivo PK properties observed in rat. In addition, we found that the chemical stability of the sulfonylureas during prolonged storage in solution was related to the sulfonyl urea linker and depended on the type of solvent and the substitution pattern of the sulfonyl urea functionality.

NOVEL PYRIDINE COMPOUNDS

The present invention relates to certain novel pyridin compounds of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.