Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane- r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent

• Published in: Bioorganic & medicinal chemistry letters 2008-10, Vol.18 (20), p.5586-5590
• Main Authors: Pingali, Harikishore, Jain, Mukul, Shah, Shailesh, Basu, Sujay, Makadia, Pankaj, Goswami, Amitgiri, Zaware, Pandurang, Patil, Pravin, Godha, Atul, Giri, Suresh, Goel, Ashish, Patel, Megha, Patel, Harilal, Patel, Pankaj
• Format: Article
• Language: English
• Subjects: 1,3-Dioxane-2 carboxylic acid; Animals; Biological and medical sciences; Carboxylic Acids - chemical synthesis; Carboxylic Acids - pharmacokinetics; Diabetes Mellitus, Type 2 - drug therapy; Dioxanes - chemical synthesis; Dioxanes - pharmacokinetics; General and cellular metabolism. Vitamins; Humans; Hypoglycemic Agents - chemical synthesis; Hypolipidemic Agents - chemical synthesis; Lipids - chemistry; Medical sciences; Mesylates - chemical synthesis; Mesylates - pharmacokinetics; Metabolic disorders; Mice; Models, Chemical; Peroxisome Proliferator-Activated Receptors - agonists; Pharmacology. Drug treatments; PPAR agonist; PPAR alpha - metabolism; PPAR gamma - metabolism; Rats; Rats, Wistar; Transcriptional Activation; Type 2 diabetes
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.08.112

A series of novel 1,3-dioxane-2-carboxylic acid derivatives have been reported as PPARα and γ agonists. Compound 13c exhibited potent hypoglycemic and lipid lowering activity and high oral bioavailability. A series of novel 1,3-dioxane-2-carboxylic acid derivatives containing alkyl chain tether and substituted phenyl group as a lipophilic tail have been prepared as agonists of PPARα and γ. c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane- r-2-carboxylic acid 13c exhibited potent hypoglycemic and lipid lowering activity with high oral bioavailability in animal models.