An overview of the preclinical toxicity and potential carcinogenicity of sitaxentan (Thelin), a potent endothelin receptor antagonist developed for pulmonary arterial hypertension was written by Owen, Keith;Cross, David M.;Derzi, Mazin;Horsley, Elizabeth;Stavros, Fiona L.. And the article was included in Regulatory Toxicology and Pharmacology in 2012.Related Products of 210421-74-2 This article mentions the following:
Sitaxentan (Thelin), an endothelin receptor antagonist with a long duration of action and high specificity for the endothelin receptor A subtype, was used to treat pulmonary arterial hypertension. It was withdrawn from the market due to an idiosyncratic risk of drug-induced liver injury identified from emerging clin. trial data and clin. case reports. The preclin. safety profile of sitaxentan is presented, including single- and repeat-dose toxicity in mice, rats, and dogs and carcinogenicity in mice and rats. Sitaxentan-related adverse effects included coagulopathy in rats and dogs, increased serum alk. phosphatase activity in mice and dogs, and hepatic hypertrophy in all species. Decreased albumin, erythrocyte count, Hb concentration and hematocrit, and increased coagulation times and liver weight were also noted. These effects generally occurred at systemic exposures (AUC0-24) that were substantially greater than those seen in humans. Twice-daily (vs. once daily) dosing resulted in increased toxicity, which correlated with increased trough plasma sitaxentan concentrations Sitaxentan appeared to have a low potential for testicular and hepatic toxicity and was not carcinogenic. These studies suggested that sitaxentan would have a reasonable margin of safety when used as directed in humans and supported a pos. benefit:risk assessment at the time of marketing approval. In the experiment, the researchers used many compounds, for example, Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2Related Products of 210421-74-2).
Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. Isoxazoles are commonly used as enaminoketone or β-diketone surrogate. Some alternative routes for the synthesis of isoxazoles have also been developed and reported. The 2-benzoyl-2-halo-2H-azirines provide 4-haloisoxazoles in good yields after heating in toluene at reflux temperature.Related Products of 210421-74-2
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem