311779-41-6

Upstream product

• 123-75-1 pyrrolidine 
• 216504-75-5 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine 
• 50-00-0 formaldehyd 
• 216504-75-5 3⁽⁵⁾-(4-fluorophenyl)-4-(4-pyridyl)pyrazole 
• 148671-39-0 3-dimethylamino-1-(4-fluorophenyl)-2-(4-pyridyl)-2-propen-1-one 

Downstream Products

• 311779-45-0 3⁽⁵⁾-(4-fluorophenyl)-5⁽³⁾-(1-hydroxy-3-(2-tolyl)propyl)-4-(4-pyridyl)-pyrazole 
• 311779-47-2 5⁽³⁾-[3-(2-chlorophenyl)-1-hydroxypropyl]-3⁽⁵⁾-(4-fluorophenyl)-4-(4-pyridyl)-pyrazole 
• 311779-51-8 3⁽⁵⁾-(4-fluorophenyl)-5⁽³⁾-[1-hydroxy-3-(2-pyridyl)propyl]-4-(4-pyridyl)-pyrazole 
• 311779-52-9 3⁽⁵⁾-(4-fluorophenyl)-5⁽³⁾-[1-hydroxy-3-(3-pyridyl)propyl]-4-(4-pyridyl)-pyrazole 
• 311779-42-7 3-(4-fluorophenyl)-5-(1-hydroxy-3-phenylpropyl)-4-(4-pyridyl)pyrazole 

Relevant academic research and scientific papers

Design and synthesis of 5-[(2-chloro-6-fluorophenyl)acetylamino]-3-(4- fluorophenyl)-4-(4-pyrimidinyl)isoxazole (AKP-001), a novel inhibitor of p38 MAP kinase with reduced side effects based on the antedrug concept

Inhibitors of p38 mitogen-activated protein (MAP) kinase, which are closely involved in the production of inflammatory cytokines, are considered promising curative drugs for chronic inflammatory disorders. However, there is also a growing concern regarding its systemic side effects. To reduce the occurrence of side effects, we have identified a novel p38 MAP kinase inhibitor that shows properties of an antedrug, which imparts its effect solely on the inflammatory site and is metabolically inactivated right after. We have designed isoxazole derivatives through the addition of a fresh interacting fourth site to the structure of the prototypical p38 MAP kinase inhibitor that harbors three point interactive sites. The derivative 26d (AKP-001) shows excellent p38 MAP kinase inhibitory activity and a high selectivity for various kinases. Its rapid metabolism has been confirmed in rats. Moreover, 26d has been shown to be effective in animal models of inflammatory bowel disease.

Substituted pyrazole compounds

Substituted pyrazole compounds represented by formula (I), or salts thereof are disclosed, wherein R1is —CH(OH)—CH(R4)—(A)n—Y, —CH2—CH(R4)—(A)n—Y, —CO—B1—A—Y or the like (wherein A is a lower alkylene; Y is an aryl group which may be substituted, for example, by halogen, or the like; R4is a hydrogen atom or a lower alkyl group; B1is —CH(R4)— or —N(R4)—; and n is 0 or 1); R2is a hydrogen atom, a lower alkyl group which may be substituted by hydroxyl or the like, or an aralkyl group; R3is a phenyl group which may be substituted by halogen or the like, or a pyridyl group; and Q is a pyridyl or quinolyl group. These substituted pyrazole compounds or their salts have an excellent p38MAP kinase inhibiting effect and are hence useful in the prevention or treatment of tumor necrosis factor α-related diseases, interleukin 1-related diseases, interleukin 6-related diseases or cyclooxygenase II-related diseases.

SUBSTITUTED PYRAZOLE COMPOUNDS

Substituted pyrazole compounds represented by formula (I), or salts thereof are disclosed, wherein R1 is -CH(OH)-CH(R4)-(A)n -Y, -CH2 -CH(R4)-(A)n-Y, -CO-B1-A-Y or the like (wherein A is a lower alkylene; Y is an aryl group which may be substituted, for example, by halogen, or the like; R4 is a hydrogen atom or a lower alkyl group; B1 is -CH(R4)- or -N(R4)-; and n is 0 or 1); R2 is a hydrogen atom, a lower alkyl group which may be substituted by hydroxyl or the like, or an aralkyl group; R3 is a phenyl group which may be substituted by halogen or the like, or a pyridyl group; and Q is a pyridyl or quinolyl group. These substituted pyrazole compounds or their salts have an excellent p38MAP kinase inhibiting effect and are hence useful in the prevention or treatment of tumor necrosis factor α-related diseases, interleukin 1-related diseases, interleukin 6-related diseases or cyclooxygenase II-related diseases.