280773-04-8

Upstream product

• 1072-98-6 5-chloro-2-pyridylamine 
• 38818-49-4 5-methyl-2-nitrobenzoyl chloride 
• 3113-72-2 5-methyl-2-nitrobenzoic acid 

Downstream Products

• 280773-05-9 N-(5-chloropyridin-2-yl)-2-amino-5-methylbenzamide 
• 1333126-80-9 N-(5-chloropyridine-2-yl)-2-[(4-etanimidoil(methyl)aminophenylcarbonyl)amino]-5-methylbenzamide 
• 1333127-02-8 N-(5-chloropyridine-2-yl)-2-[(4-methylaminophenylcarbonyl)amino]-5-methylbenzamide 
• 1333127-01-7 N-(5-chloropyridine-2-yl)-2-[(4-methyl(trifluoroacetyl)aminophenylcarbonyl)amino]-5-methylbenzamide 
• 330940-83-5 N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-methylphenyl}[4-(1-methyl(2-imidazolin-2-yl))phenyl]carboxamide 

Relevant academic research and scientific papers

PHARMACEUTICAL COMPOSITIONS COMPRISING ANTICOAGULANT N-(5-CHLOROPYRIDINE-2-YL)-2-({4-[ETHANIMIDOIL(METHYL)AMINO]BENZOYL}AMINO)-5-METHYLBENZAMIDE

The invention relates to area of medicine, in particular to pharmacology, namely to novel pharmaceutical compositions for oral use for treatment of diseases associated with increased thrombus formation. The compositions comprise the anticoagulant N-(5-chloropyridine-2-yl)-2-({4-[ethanimidoil(methyl)amino]benzoyl}amino)-5-methylbenzamide or a pharmaceutically acceptable salt thereof, being a factor Xa inhibitor and polyprenol, and are protected from the contact with acidic gastric juice by an enteric coating or capsule. The compositions are of high efficacy and bioavailability and can be used to treat and prevent conditions characterized by undesirable thrombosis.

Benzamides and related inhibitors of factor Xa

Novel benzamide compounds including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating coagulation disorders.

URETHANES, UREAS, AMIDINES AND RELATED INHIBITORS OF FACTOR XA

The invention relates to a new class of compounds, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions that are effective as selective inhibitors of factor Xa, both in the isolated state and in a complex with other proteins. The compounds of the invention can be used for treating and preventing diseases, such as acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, thromboses caused by post-thrombolytic therapy or coronary angioplasty, acute ischemia mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, and other diseases in humans and other mammals associated with blood coagulation problems.

Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor

Systematic SAR studies of in vitro factor Xa inhibitory activity around compound 1 were performed by modifying each of the three phenyl rings. A class of highly potent, selective, efficacious and orally bioavailable direct factor Xa inhibitors was discovered. These compounds were screened in hERG binding assays to examine the effects of substitution groups on the hERG channel affinity. From the leading compounds, betrixaban (compound 11, PRT054021) has been selected as the clinical candidate for development.

Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors

Compound 1 was identified by high throughput screening as a novel, potent, non-amidine factor Xa inhibitor with good selectivity against thrombin and trypsin. A series of modifications of the three aromatic groups of 1 was investigated. Substitution of chlorine or bromine for fluorine on the aniline ring led to the discovery of subnanomolar factor Xa inhibitors. Positions on the anthranilic acid ring that can accommodate further substitution were also identified.