Tibric acid explained

Tibric acid is a sulfamylbenzoic acid that acts as a hypolipidemic agent.^[1] Although it was found to be more powerful than clofibrate in lowering lipid levels, it was found to cause liver cancer in mice and rats, and so was not introduced as a human drug.^[2] In rats it causes an increase in peroxisomes, and liver enlargement, and then liver cancer. However the peroxisome changes do not occur in humans, and it is not likely to cause liver cancer in humans.^{[3] [4]}

Synthesis

Tibric acid can be made in a multi-step process. Firstly 2-chlorobenzoic acid is reacted with chlorosulfonic acid to add a chlorosulfonate group in the 5- position. This reacts with 3,5-dimethylpiperidine to yield tibric acid.^[5]

Notes and References

1. Book: Bencze. W. L.. Kritchevsky. D.. Dempsey. M. E.. Eisenberg. S.. Felts. J. M.. Frantz. I. D.. Hess. R.. Levy. R. I.. Miettinen. T. A.. Rudel. L. L.. Sodhi. H. S.. Stäubli. W.. Zemplényi. T.. Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques . Hypolipidemic Agents . Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progres des Recherches Pharmaceutiques. 2012. 13. 217–292. Springer Science & Business Media. 10.1007/978-3-0348-7068-9_5. 9783642661907. 4982663. https://books.google.com/books?id=a1bmCAAAQBAJ&pg=PA390. en.
2. Lalloyer. F.. Staels. B.. Fibrates, Glitazones, and Peroxisome Proliferator-Activated Receptors. Arteriosclerosis, Thrombosis, and Vascular Biology. 14 April 2010. 30. 5. 894–899. 10.1161/ATVBAHA.108.179689. 20393155. 2997800.
3. Cohen. A.J.. Grasso. P.. Review of the hepatic response to hypolipidaemic drugs in rodents and assessment of its toxicological significance to man. Food and Cosmetics Toxicology. January 1981. 19. 5. 585–605. 10.1016/0015-6264(81)90509-5. 7030887.
4. Lai. David Y.. Rodent Carcinogenicity of Peroxisome Proliferators and Issues on Human Relevance. Journal of Environmental Science and Health, Part C. 26 December 2004. 22. 1. 37–55. 10.1081/GNC-120038005. 15845221. 2004JESHC..22...37L . 23950095.
5. Book: Lednicer. Daniel. Mitscher. Lester A.. Georg. Gunda I.. The Organic Chemistry of Drug Synthesis. 1977. John Wiley & Sons. 9780471043928. 87. en.