503071-67-8

Upstream product

• 34837-84-8 4-fluorobenzeneacetic acid methyl ester 
• 1074-68-6 4-formyl-2-(methylthio)pyrimidine 
• 503071-70-3 2-(4-fluorophenyl)-3-hydroxy-3-(2-methylsulfanyl-pyrimidin-4-yl)-propionic acid methyl ester 

Downstream Products

• 607721-43-7 4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1,2-dihydro-pyrazol-3-one 
• 853223-12-8 1,2-diethyl-4-(4-fluoro-phenyl)-5-(2-methylsulfanyl-pyrimidin-4-yl)-1,2-dihydro-pyrazol-3-one 
• 476313-98-1 4-(4-fluorophenyl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-2H-isoxazol-5-one 
• 607721-72-2 4-(4-fluorophenyl)-1,2-dimethyl-5-(2-methylsulfanyl-pyrimidin-4-yl)-1,2-dihydropyrazol-3-one 

Relevant academic research and scientific papers

Convergent synthesis of 2,3-bisarylpyrazolones through cyclization of bisacylated pyrazolidines and hydrazines

Cyclization of various bisacylated hydrazines and pyrazolidines using DBU or sodium hydride leads to the formation of various mono-, bi- and tricyclic pyrazolone scaffolds in 41-98% yield. The convergent nature by which the precyclization intermediates are constructed allows for rapid derivatization about the pyrazolone core.

6,7-Dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines

The present invention relates to methods for treating diseases or disease states which are mediated or otherwise affected by the extracellular release of cytokines, said method comprising the step of administering to a human or higher mammal in need of treatment, one or more of the 6,7-dihydro-5H-pyrazolo[1,2a]pyrazol-1-ones of the present invention.

The development of new isoxazolone based inhibitors of tumor necrosis factor-alpha (TNF-α) production

4-Aryl-3-pyridyl and 4-aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-α) inhibitors, which contain a novel isoxazolone five-membered heterocyclic core are described. Many showed sub-micromolar activity against lipopolysaccharide-induced TNF-α production.

The development of monocyclic pyrazolone based cytokine synthesis inhibitors

4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-α production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo model of osteoarthritis. The X-ray crystal structure of a pyrazolone inhibitor cocrystallized with mutated p38 (mp38) is presented.

6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines

The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: wherein R1 is substituted aryl; R4 is substituted or unsubstituted aryl or heteroaryl.

6,7-Dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which provide analgesia

The present invention relates to compound which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, including all enantiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: 1wherein R comprises ethers or amines; R1 is: a) substituted or unsubstituted aryl; or b) substituted or unsubstituted heteroaryl; each R2 unit is independently selected from the group consisting of: a) hydrogen; b) —(CH2)jO(CH2)nR8; c) —(CH2)jNR9aR9b; d) —(CH2)jCO2R10; e) —(CH2)jOCO2R10 f) —(CH2)jCON(R10)2; g) —(CH2)jOCON(R10)2; h) two R2 units can be taken together to form a carbonyl unit; i) and mixtures thereof; R8, R9a, R9b, and R10 are each independently hydrogen, C1-C4 alkyl, and mixtures thereof; R9a and R9b can be taken together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; two R10 units can be take together to form a carbocyclic or heterocyclic ring comprising from 3 to 7 atoms; j is an index from 0 to 5, n is an index from 0 to 5; Z is O, S, NR11, or NOR11; R11 is hydrogen or C1-C4 alkyl.

The development of new bicyclic pyrazole-based cytokine synthesis inhibitors

4-Aryl-5-pyrimidyl-based cytokine synthesis inhibitors of TNF-α production, which contain a novel bicyclic pyrazole heterocyclic core, are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-α production in a THP-1 cell-based assay and against human p38α MAP kinase in an isolated enzyme assay. The X-ray crystal structure of a bicyclic pyrazole inhibitor co-crystallized with mutated p38 (mp38) is presented. 4-Aryl-5-pyrimidyl-based cytokine synthesis inhibitors of TNF-α production, which contain a novel bicyclic pyrazole heterocyclic core, are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-α production in a THP-1 cell-based assay and against human p38α MAP kinase in an isolated enzyme assay. The X-ray crystal structure of a bicyclic pyrazole inhibitor co-crystallized with mutated p38 (mp38) is presented.

1,2-dihydropyrazol-3-ones which controls inflammatory cytokines

The present invention relates to compounds which are capable of preventing the extracellular release of inflammatory cytokines, said compounds, or enantiomeric and diasteriomeric forms or pharmaceutically acceptable salts thereof, have the formula: wherein R is an ether or amino unit, R1 is substituted phenyl, each R2 and R3 unit is independently selected from the group consisting of: a) hydrogen; and b) substituted or unsubstituted C1-C10 hydrocarbyl selected from the group consisting of: i) C1-C10 linear, branched or cyclic alkyl; ii) C1-C10 aryl; iii) C1-C10 heterocyclic; iv) C1-C10 heteroaryl.

Isoxazolone compounds useful in treating diseases associated with unwanted cytokine activity

Isoxazolone compounds having the generic structure: are used to treat disease associated with unwanted cytokine activity, including rheumatoid arthritis, osteoarthritis, diabetes, HIV/AIDS, inflammatory bowel disease, Crohn's disease, ulcerative colitis,