A Facile One-Pot Synthesis of 4-Alkoxy-1,3-benzenedicarbonitrile

Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase

“…1) is a non-purine, XO inhibitor (Hasegawa, 1998) currently under clinical evaluation for the treatment of hyperuricemia and gout (Kamatani et al, 2003;Schumacher et al, 2002). We previously reported that febuxostat is a potent, mixed-type inhibitor of bovine milk XO (Ki = 0.7 nM) in vitro and had a potent in vivo hypouricemic effect in rodents Horiuchi et al, 1999) and chimpanzees .…”

Synthetic approaches to the 2009 new drugs

“…49,50 There are a number of routes available to prepare this agent as discussed in recent publications. 51,52 The synthesis shown in Scheme 10 is a short and concise route and does not require the use of toxic reagents. 53 Thus the commercially available and easily prepared 4-hydroxythiobenzamide (52) was reacted with ethyl bromoacetoacetate (53) in refluxing ethanol to provide the thiazole ester 54 in $60% yield after crystallization.…”

Febuxostat ethanol monosolvate

“…The current study was carried out as part of an investigation with the aim of establishing a modified synthetic route for febuxostat (Lutra et al, 2012), avoiding harsh conditions, toxic reagents to form the thioamide and the highly toxic cyanides. One of the key aspects of the novel route of synthesis was the introduction of a modified version of the Duff reaction (Duff & Bills, 1932, 1934 in the first step, which finally resulted in improved overall yields compared to the original synthesis by Hasegawa (1998).…”

“…The preparation of febuxostat was carried out according to the scheme in Fig. 3 in a modified procedure based on the original synthesis by Hasegawa (1998).…”