Prostaglandin isosteres. 2. Chain-modified thiazolidinone prostaglandin analogs as renal vasodilators

• Published in: Journal of medicinal chemistry Vol. 26; no. 3; pp. 342 - 348
• Main Authors: Bicking, John B, Bock, Mark G, Cragoe, Edward J, DiPardo, Robert M, Gould, Norman, Holtz, Wilbur J, Lee, T. J, Robb, Charles M, Smith, Robert L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.1983
• Subjects: Animals; Dogs; Female; Kidney - blood supply; Models, Molecular; Regional Blood Flow - drug effects; Stereoisomerism; Thiazoles - pharmacology; Thiazolidines; Vascular Resistance - drug effects; Vasodilation - drug effects; X-Ray Diffraction
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00357a006

Chain modification of a thiazolidinone prostaglandin isostere has led to the production of 4-[3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl]propyl] benzoic acid (5b) which at 1 mg/kg po in the conscious dog causes a 70% increase in renal blood flow over control values with a duration of action exceeding 5 h. Preliminary testing indicates that 5b has a relatively specific action on the vasculature of the kidney. The enantiomers of 5b have been separated and the renal vasodilatory activity has been found to be entirely a property of the R-(+) enantiomer.