A series of novel sulphonamides have been discovered which show high affinity and selectivity for the endothelin ETA receptor. N-Methyl-2-[4-(2-methylpropyl)phenyl]-3-(3-methoxy-5-methylpyrazin-2-ylsulfamoyl)benzamide (18) is the most widely investigated compound and is a potent antagonist in vivo when dosed either i. v. or orally, and has prolonged oral duration of action.

AbstractDie Pyridine (I) reagieren mit dem Acetylen (II) in Acetonitril zu den Cyclobutapyridinen (III).

AbstractDie 1‐Alkyl‐1,4‐dihydropyridine (Ia)‐(Ic) reagieren mit Acetylen‐dicarbonsäure‐dimethylester (II) zu den Cycloaddukten (IIIa)‐(IIIc).

Several 1,3-disubstituted 1,4-dihydropyridines with dimethyl acetylenedicarboxylate in acetonitrile at room temperature gave 1,4,4a,6a-tetrahydrocyclobuta[b]pyridines and where a 3-carboxy- or a 3-carbamoyl group was present, a novel cycloelimination of this group occurred to give the corresponding 3-(cis-1,2-dimethoxycarbonylvinyl) derivative. 1-Benzyl-1,4-dihydroquinoline-4-carbonitrile gave the 3-(cis-1,2-dimethoxycarbonylvinyl) derivative quantitatively, and 2-benzyl-1,2-dihydroisoquinoline-1-carbonitrile formed a phenanthridine.

Several 1,3-disubstituted-1,4-dihydropyridines with dimethyl acetylenedicarboxylate gave 1-azabicyclo-[4,2,0]octa-2,5-dienes, and where a 3-CO2H or a 3-CONHR group was present elimination of this group occurred through a 6-membered cyclic transition state in each case to give the corresponding 3-(cis-1,2-dimethoxycarbonylvinyl) derivative.