775344-72-4

Upstream product

• 264607-27-4 5-chloro-N-hydroxyfuran-2-carbonimidoyl chloride 
• 103-79-7 1-phenyl-acetone 
• 181696-73-1 3,4-diphenyl-4-hydrido-5-hydroxy-5-methylisoxazole 

Downstream Products

• 1171190-73-0 3-(furan-2-yl)-5-methyl-4-phenylisoxazole 
• 1171190-77-4 5-methyl-4-phenyl-3-(tetrahydrofuran-2-yl)isoxazole 
• 1171190-78-5 3-(5-bromofuran-2-yl)-5-methyl-4-phenylisoxazole 
• 57352-08-6 (Z)-4-amino-4-(furan-2-yl)-3-phenylbut-3-en-2-one 
• 1372779-73-1 (Z)-4-amino-4-(5-chlorofuran-2-yl)-3-phenylbut-3-en-2-one 
• 1579976-80-9 5-(bromomethyl)-3-(5-chlorofuran-2-yl)-4-phenylisoxazole 
• 1579976-83-2 2-[3-(5-chlorofuran-2-yl)-4-phenylisoxazol-5-yl]acetic acid 
• 1613135-53-7 5-(fluoromethyl)-3-(5-chlorofuran-2-yl)-4-phenylisoxazole 

Relevant academic research and scientific papers

Structural basis for selective inhibition of Cyclooxygenase-1 (COX-1) by diarylisoxazoles mofezolac and 3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6)

The diarylisoxazole molecular scaffold is found in several NSAIDs, especially those with high selectivity for COX-1. Here, we have determined the structural basis for COX-1 binding to two diarylisoxazoles: mofezolac, which is polar and ionizable, and 3-(5

Synthesis, pharmacological characterization, and docking analysis of a novel family of diarylisoxazoles as highly selective cyclooxygenase-1 (COX-1) inhibitors

3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a known selective cyclooxygenase-1 (COX-1) inhibitor, was used to design a new series of 3,4-diarylisoxazoles in order to improve its biochemical COX-1 selectivity and antiplatelet efficacy. Structure-activity relationships were studied using human whole blood assays for COX-1 and COX-2 inhibition in vitro, and results showed that the simultaneous presence of 5-methyl (or -CF3), 4-phenyl, and 5-chloro(-bromo or -methyl)furan-2-yl groups on the isoxazole core was essential for their selectivity toward COX-1. 3g, 3s, 3d were potent and selective COX-1 inhibitors that affected platelet aggregation in vitro through the inhibition of COX-1-dependent thromboxane (TX) A2. Moreover, we characterized their kinetics of COX-1 inhibition. 3g, 3s, and 3d were more potent inhibitors of platelet COX-1 and aggregation than P6 (named 6) for their tighter binding to the enzyme. The pharmacological results were supported by docking simulations. The oral administration of 3d to mice translated into preferential inhibition of platelet-derived TXA2 over protective vascular-derived prostacyclin (PGI2).

Functionalized diarylisoxazoles inhibitors of ciclooxygenase

The present invention refers to isoxazole derivatives, in particular diarylisoxazole derivatives inhibitors of cyclooxygenase (COX), in particular cyclooxygenase-1 (COX-1), to their pharmaceutical compositions, the process for their preparation and their use for the chemoprevention and treatment of inflammatory syndromes and in the prevention and treatment of carcinomas, in particular intestinal, ovarian and cutaneous carcinomas, in the treatment of pain syndromes, in particular after surgery, and in the cardiovascular field as antithrombotics/vasoprotectives/cardioprotectives.

ISOXAZOLE DERIVATIVES AND THEIR USE AS CYCLOOXYGENASE INHIBITORS

The present invention refers to isoxazole derivatives, in particular 3,4-diaryl isoxazole derivatives, to their pharmaceutical compositions, the process for preparing them and their use as inhibitors of cycloosygenase, in particular of cycloosygenase 1 and 2 (COX-1) (COX-2). The present invention also refers to a process for determining the potential toxicity of compounds that inhibit cycloosygenase (COX), in particular cycloosygenase-2 (COX-2) isoform, and to the use of compounds that inhibit cycloosygenase (COX), in particular cycloosygenase-2 (COX-2) and their pharmaceutical compositions, in subjects for whom the potential cardiovascular toxicity of said compounds is reduced.

Novel synthesis of 3,4-diarylisoxazole analogues of valdecoxib: Reversal cyclooxygenase-2 selectivity by sulfonamide group removal

3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol- 4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition of arylnitrile oxides to the enolate ion of phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 °C. The corresponding 3-aryl-5-methyl-4-phenyl- isoxazoles were easily generated by a dehydration/aromatization reaction under basic conditions of 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines and further transformed into their benzenesulfonamide derivatives. The biochemical COX-1/COX-2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity. Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX-1 inhibitors.