Dual PPAR-alpha and -gamma activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential.
2,4-Thiazolidinedione derivatives of 1,3-benzoxazinone were synthesized and evaluated for their PPAR-alpha and -gamma dual activation. DRF-2519, a compound obtained through SAR of TZD derivatives of benzoxazinone, has shown potent dual PPAR activation. In ob/ob mice, it showed better efficacy than the comparator molecules. In fat fed rat model, it showed significant improvement in lipid parameters, which was better than fibrates.
Madhavan
Gurram R
GR
Discovery Chemistry, Dr. Reddy's Laboratories Ltd., Bollarum Road, Miyapur, Hyderabad 500049, India. madhavangr@rediffmail.com
Chakrabarti
Ranjan
R
Reddy
K Anantha
KA
Rajesh
B M
BM
Balraju
V
V
Rao
P Bheema
PB
Rajagopalan
R
R
Iqbal
Javed
J
D000818:Animals; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones