773104-02-2

Upstream product

• 23915-07-3 1-(bromomethyl)-2,4-difluorobenzene 
• 773104-01-1 3-(4-hydroxy-2-methylsulfanyl-6-oxo-6H-pyrimidin-1-yl)-4-methyl-benzoic acid methyl ester 
• 18595-18-1 3-amino-4-methyl benzoic acid methyl ester 
• 1093071-69-2 C₁₁H₁₆N₂O₂S 
• 773104-00-0 methyl 3-[(aminocarbonothioyl)amino]-4-methylbenzoate 

Downstream Products

• 773103-49-4 C₂₂H₂₀ClF₂N₃O₅ 
• 773104-06-6 C₁₉H₁₄F₂N₂O₄ 
• 773104-07-7 3-[5-chloro-4-(2,4-difluorobenzyloxy)-6-oxo-6H-pyrimidin-1-yl]-4-methylbenzoic acid 
• 944154-49-8 3-[5-chloro-4-(2,4-difluoro-benzyloxy)-2-methylsulfanyl-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid 
• 1093071-71-6 C₂₀H₁₅ClF₂N₂O₅S 
• 1093071-70-5 C₂₀H₁₅ClF₂N₂O₆S 
• 1093071-59-0 3-[5-chloro-4-(2,4-difluorobenzyloxy)-6-oxo-6H-pyrimidin-1-yl]-N-[(R)-2-(2-methoxyethyl)-3-oxo-isoxazolidin-4-yl]-4-methylbenzamide 

Relevant academic research and scientific papers

Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-α in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.

KINASE INHIBITOR COMPOUNDS

Pyrimidinone derivatives have enhanced and unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as inflammatory diseases and certain types of cancer.

PYRIMIDINONE DERIVATIVES AS PROTEIN KINASE INHIBITORS

Pyrimidinone derivatives have enhanced and unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as inflammatory diseases and certain types of cancer.

SUBSTITUTED PYRIMIDINONES

Disclosed are compounds Formula I and pharmaceutically acceptable salts thereof, wherein R1, R2, R4, and R5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.