Y-700, a Novel Inhibitor of Xanthine Oxidase, Suppresses the Development of Colon Aberrant Crypt Foci and Cell Proliferation in 1,2-Dimethylhydrazine-Treated Mice

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

“…3) are reported to have a favorable toxicology profile, high bioavailability, and more potent and longer-lasting hypouricemic action than allopurinol. These new compounds are currently in human clinical trials for the treatment of hyperuricemia and gout Yamamoto, 2003;Becker et al, 2004;Hoshide et al, 2004;Komoriya et al, 2004;Yamada et al, 2004;Hashimoto et al, 2005;Mayer et al, 2005;Takano et al, 2005).…”

“…There are a few structural classes of compounds that are many hundreds times more potent than allopurinol in vitro (both of a purine and nonpurine types). Several drug candidates are either in the development phase or are moving toward clinical testing (Borges et al, 2002;Naito et al, 2000;Okamoto et al, 2003;Nivorozhkin et al, 2003a,b;Yamamoto, 2003;Mabley et al, 2003;Becker et al, 2004;Fukunari et al, 2004;Hoshide et al, 2004;Komoriya et al, 2004;Yamada et al, 2004;Hashimoto et al, 2005;Mayer et al, 2005;Takano et al, 2005). It was clearly established that a xanthine-like structural framework is not a prerequisite for high inhibitory activity.…”

“…From the small number of current examples of the development of novel XO inhibitor compounds that have entered a clinical phase (Becker et al, 2004Fukunari et al, 2004;Komoriya et al, 2004;Yamada et al, 2004;Hashimoto et al, 2005;Mayer et al, 2005;Takano et al, 2005), it appears that hyperuricemia and gout remain the main indications for the development of novel XO inhibitors, with additional growing interest in cardiac indications, such as chronic heart failure. Novel XO inhibitors must preferably be more potent, more effective, and possess better pharmacodynamic profile than allopurinol/oxypurinol, which is expected to translate in the clinical practice to lower daily doses and/or less frequent daily administration of the drug.…”

“…It is noteworthy that, so far, practically all published efficacy data associated with the novel XO inhibitor compounds relate to the area of gout, and researchers have not tested or reported efficacy of these compounds in preclinical models of inflammation or reperfusion or toxic organ injury Yamamoto, 2003;Becker et al, 2004;Fukunari et al, 2004;Hoshide et al, 2004;Komoriya et al, 2004;Yamada et al, 2004;Hashimoto et al, 2005;Mayer et al, 2005;Takano et al, 2005). The XO inhibitor pterin-6-aldehyde is a known superoxide scavenger and probably so are the 2-alkyloxyalkylthiohypoxanthines as well (Biagi et al, 2001).…”

Novel thiazolo-pyrazolyl derivatives as xanthine oxidase inhibitors and free radical scavengers

“…FYX-051 (9) reported by Takahiro Sato et al is currently being evaluated in phase 2 clinical trial [18]. Y-700 (10) [19] N-aryl-5-amino-4-cyanopyrazole (11) [20], flavonoids (12) [21], anacardic acid (13) [22] and curcumin (14) [23] also reported to be potent xanthine oxidase inhibitor. Our consistent work on heterocycles [24][25][26] having potent biological activities, prompted us to prepare new thiazolopyrazolyl derivatives bearing different functional moieties and expected to possess potent XO inhibitory activity comparable to Allopurinol along with antioxidant effect.…”