Synthesis and biological activity of carboxyl-terminus modified prostaglandin analogues

Article abstract of DOI:10.1021/jm00197a012

A series of PGE₂, 16,16-dimethyl-PGE₂, and PGF(2α), and PGF(2α) analogues modified at the carboxyl terminus with tetrazole, amide, acylurea, imide, and sulfonimide functionalities was evaluated for uterine stimulant, bronchodilator, hypotensive, gastric antisecretory, and diarrheal activity. These compounds were prepared by modification of the Corey prostaglandin synthesis utilizing as a key step condensation of known hemiacetals with the ylide derived from the requisite substituted phosphonium salts. Structure-activity relationships suggest that a proton at the C-1 position appears necessary for agonist activity and the acidity of this proton has a relatively greater influence on activity than pendant steric bulk. Noteworthy are the tissue-selective bronchodilator activity of N-acetyl-PGE₂-carboxamide and the selectivity for uterine tissue of N-methanesulfonyl-PGE₂-carboxamide, 2-decarboxy-2-(tetrazol-5-yl)-16,16-dimethyl-PGE₂, N-acetyl-16,16-dimethyl-PGE₂-carboxamide, and N-methanesulfony-PGE₂-carboxamide, and N-methanesulfonyl-16,16-dimethyl-PGE₂-carboxamide.