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Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4′-position. Introduction of an amino group at the 2′-position also led to improved analogues. Combination of the optimal 4′- isobutyl substituent with the 2′-amino function afforded an analogue (20, BMS-187308) with improved ET(A) binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 mumol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.
Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.Read on for other articles about 141-30-0Related Products of 141-30-0
Reference：
Pyridazine – Wikipedia,
Pyridazine | C4H4N1832 – PubChem