916590-30-2

Upstream product

• 4509-90-4 5-bromovaleroyl chloride 
• 29632-74-4 2-fluro-4-iodoaniline 
• 1101046-55-2 1-(4-amine-2-fluorophenyl)piperidin-2-one 
• 675-20-7 piperidin-2-one 
• 369-34-6 3,4-difluoronitrobenzene 

Downstream Products

• 916591-48-5 3,3-dichloro-1-(2-fluoro-4-iodo-phenyl)-piperidin-2-one 
• 280120-51-6 2-fluoro-5-[6-(3-fluoro-2'-formyl-biphenyl-4-yl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-benzonitrile 
• 905931-55-7 2-fluoro-5-[6-(2-fluoro-4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-benzonitrile 
• 905931-54-6 1-(2-fluoro-4-iodo-phenyl)-4-trifluoroacetyl-piperidine-2,3-dione 
• 905931-53-5 1-(2-fluoro-4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one 

Relevant academic research and scientific papers

4,5-dihydropyrazolo [3,4-c] pyridine-2-one spiro derivatives, its preparation method and application

Disclosed are a spirocyclic derivative of 4,5-dihydropyrazolo[3,4-c]pyridine-2-one as represented by general formula (I), preparation method and use thereof, the definition of each substituent in the compound of general formula (I) being the same as the definition in the description.

1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa

Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety. Scaffold optimization resulted in the identification of a novel bicyclic pyrazolo-pyridinone scaffold which retained fXa potency. The novel bicyclic scaffold preserved all binding interactions observed with the monocyclic counterpart and importantly the carboxamido moiety was integrated within the scaffold making it less susceptible to hydrolysis. These efforts led to the identification of 1-[3-aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one 6f (BMS-740808), a highly potent (fXa Ki = 30 pM) with a rapid onset of inhibition (2.7 × 107 M-1 s-1) in vitro, selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood coagulation factor Xa.