11,12-Secoprostaglandins. 3. 8-Alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids and related compounds.
A series of 8-alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids which embody structural features of 11,12-secoprostaglandins was synthesized and evaluated for their ability to mimic the E series prostaglandins in stimulating cAMP formation in the mouse ovary and in binding to the rat lipocyte prostaglandin receptor. A key member of the series, 8-methylsulfonyl-12-hydroxyheptadecanoic acid, markedly stimulated cAMP formation at reasonable pharmacological concentrations, shows significant affinity for a prostaglandin receptor, and effectively inhibits antigen-induced lymphocyte transformation. In contrast, this compound is not a substrate for 15-hydroxyprostaglandin dehydrogenase, the major prostaglandin-metabolizing enzyme.
D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004285:Dogs; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011565:Psoriasis / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP