11,12-Secoprostaglandins. 1. Acylhydroxyalkanoic acids and related compounds

• Published in: Journal of medicinal chemistry Vol. 20; no. 1; pp. 35 - 43
• Main Authors: Bicking, John B, Robb, Charles M, Smith, Robert L, Cragoe, Edward J, Kuehl, Frederick A, Mandel, Lewis R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.1977
• Subjects: Animals; Binding Sites; Cyclic AMP - biosynthesis; Fatty Alcohols - chemical synthesis; Female; Mice; Ovary - drug effects; Ovary - metabolism; Prostaglandins - analysis; Prostaglandins - chemical synthesis; Prostaglandins - pharmacology; Rats; Receptors, Prostaglandin; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00211a007

The synthesis is described of a series of acylhydroxyalkanoic acids which embody structural modifications of that class of secoprostaglandins which are formally derived from the natural substances by scission of the cyclopentane ring between carbon atoms 11 and 12. These analogues have been tested for their ability to stimulate cAMP formation in the mouse ovary, a characteristic action of the (E)-prostaglandins, and for their ability to bind to the rat lipocyte prostaglandin receptor. Certain members of the series that most closely resemble the prostaglandins in structure (e.g., 8-acetyl-12-hydroxyheptadecanoic acid) markedly stimulate cAMP formation at concentrations in the pharmacological range and show a significant affinity for the prostaglandin receptor. Conversely, these compounds are not substrates for prostaglandin 15-hydroxydehydrogenase which catalyzes a major reaction in the biological deactivation of the prostaglandins.