Tezosentan Actelion

Novel sulfonamides are claimed which are endothelin receptor inhibitors. They are potentially useful for the treatment of disorders which are associated with endothelin activities, especially circulatory disorders such as hypertension, ischemia, vasospasm and angina pectoris. Processes by which there compounds may be synthesized are claimed. Six compounds were shown to inhibit the binding of endothelin to recombinant endothelin receptors. Data are presented in one table. IC₅₀ values ranged from 1 to 6 nM, the former being exhibited by the specified compound. These six compounds also inhibited endothelin-induced contractions in isolated rat aorta rings. Six processes by which these compounds may be synthesized are described. 75 Compounds are exemplified by syntheses, including the specified compound, 2-[6-(1,3-benzodioxol-5-ylsulfonylamino)-5-(2-methoxyphenoxy)-2-2-1H-(tetrazol-5 -yl)-pyri-din-4-yl)-pyrimidin-4-yloxy]-ethylpyridin-2-yl-carbam-ate, which is one of 82 compounds specifically claimed.