Synthesis of some 5-phenylisoxazole-3-carboxylic acid derivatives as potent xanthine oxidase inhibitors

Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives as non-purine xanthine oxidase inhibitors

“…Therefore, the presence of a butoxy group (n-butoxy, secbutoxy, or iso-butoxy) at the 4 0 -position benefited the XO inhibitory potency of 1-hydroxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives. This finding was also true for 1-phenylpyrazoles [6] and 5-phenylisoxazoles [8] XO inhibitors. A dose-dependent inhibition of representative compound 4f on XO was exhibited (Fig.…”

“…In continuation of our previous efforts on finding novel nonpurine XO inhibitors [8], we had designed and synthesized a series of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-for most of the 1-hydroxy substituted compounds 4ae4k and 1-methoxy substituted compounds 6ae6k, respectively. Moreover, the 1-methoxy group of imidazole was observed as a singlet at around 3.95 ppm for 1-methoxy substituted compounds 6ae6k.…”

“…Therefore, identifying some novel non-purine XO inhibitors with potent XO inhibitory potency and fewer side effects is extremely necessary. In fact, some excellent non-purine XO inhibitors have been reported in the recent literature, including carboxyl moiety containing inhibitors, such as Febuxostat [5], Y-700 [6], selenazoles [7], isoxazoles [8] and 2-(indol-5-yl)thiazoles [9]; and non-carboxyl moiety containing inhibitors, like Topiroxostat [10], isocytosines [11e13], N-(1,3-diaryl-3-oxopropyl)amides [14], N-1-acetyl-3,5-diaryl-4,5-dihydro-(1H) pyrazoles [15], naphthoflavones [16], 2-amino-5-alkylidene-thiazol-4-ones [17], azaflavones [18], naphthopyrans [19], 4,6-diaryl/ heteroarylpyrimidin-2(1H)-ones [20], and 2,4-diaryl-pyrano [3,2-c] chromen-5(4H)-one [21] (Fig. 1).…”

Development of 2‐(Substituted Benzylamino)‐4‐Methyl‐1, 3‐Thiazole‐5‐Carboxylic Acid Derivatives as Xanthine Oxidase Inhibitors and Free Radical Scavengers

“…Development of XO inhibitors with free radical scavengers potential may prove to be promising agents to treat Gout. This encouraged the researchers to develop structurally diverse molecules without purine backbone with promising XO inhibitory activity such as N‐(1,3‐diaryl‐3‐oxopropyl) amides ( 4 ) ,1‐acetyl‐3,5‐diaryl‐4,5‐di‐hydrol(1H) pyrazoles ( 5 ) , Y‐700 ( 6 ) , N‐aryl‐5‐amino‐4‐cyanopyrazole (7) , flavonoids ( 8 ) , anacardic acid ( 9) , thiazolo‐pyrazolyl 5‐phenylisoxazole‐3‐carboxylic acid ( 10 ) , naphthoflavones ( 11 ) , and pyrazolo[3,4‐d] thiazolo[3,2‐a]pyrimidin‐4‐one ( 12 ) , 2‐(3‐cyano‐2‐isopropyl‐1H‐indol‐5‐yl)‐4‐methylthiazole‐5‐carboxylic acid ( 13 ) , derivatives (Figure ). It was assumed worthwhile to rationally design with pharmacophoric approaches to develop structural analogous of febuxostat as non‐purine XO inhibitors with antioxidant activity for diminishing the associated toxicities.…”

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

“…Isoxazole derivatives 136 with similar substitutions to febuxostat and Y-700 were explored by Wang et al [107] Al ibrary of five derivatives with an itro group at position R 1 and five derivatives with ac yano group at the same positionweresynthesized and tested in vitro against XO. The compounds with the cyano group always showed better activity than the compoundsw ith the nitro group.…”