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.
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 PPARalpha and gamma. 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.
Pingali
Harikishore
H
Zydus Research Centre, Sarkhej-Bavla N.H 8A Moraiya, Ahmedabad 382210, India.
Jain
Mukul
M
Shah
Shailesh
S
Basu
Sujay
S
Makadia
Pankaj
P
Goswami
Amitgiri
A
Zaware
Pandurang
P
Patil
Pravin
P
Godha
Atul
A
Giri
Suresh
S
Goel
Ashish
A
Patel
Megha
M
Patel
Harilal
H
Patel
Pankaj
P
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004146:Dioxanes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis*; D008055:Lipids / Q000737:chemistry; D008698:Mesylates / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051379:Mice; D008956:Models, Chemical; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D051381:Rats; D017208:Rats, Wistar; D015533:Transcriptional Activation
C540066:5-(6-(4-methanesulfonyloxyphenyl)hexyl)-2-methyl-1,3-dioxane-2-carboxylic acid; D002264:Carboxylic Acids; D004146:Dioxanes; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008055:Lipids; D008698:Mesylates; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors