Synthesis and biological activity of carboxyl-terminus modified prostaglandin analogs

A series of PGE2, 16,16-dimethyl-PGE2, and PGF2 alpha 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 w...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1979-11, Vol.22 (11), p.1340-1346
Main Authors: Schaaf, Thomas K, Hess, Hans Juergen
Format: Article
Language:English
Subjects:
Animals
Blood Pressure - drug effects
Bronchodilator Agents - chemical synthesis
Diarrhea - chemically induced
Dogs
Female
Gastric Juice - metabolism
Guinea Pigs
In Vitro Techniques
Male
Mice
Prostaglandins E, Synthetic - chemical synthesis
Prostaglandins E, Synthetic - pharmacology
Prostaglandins F, Synthetic - chemical synthesis
Prostaglandins F, Synthetic - pharmacology
Rats
Structure-Activity Relationship
Uterine Contraction - drug effects
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of PGE2, 16,16-dimethyl-PGE2, and PGF2 alpha 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-methanesulfonyl-16,16-dimethyl-PGE2-carboxamide.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00197a012