Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents.
A series of novel dibenzo[b,d]furan mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit Protein Tyrosine Phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Structure-activity relationship study led to the identification of potent compound 5 E which inhibited PTP1B with IC(50) value of 82+/-0.43 nM. Compound 5 E was screened in vivo as drug candidate for anti-diabetic activity using rosiglitazone maleate as the standard. Compound 5 E showed significant reduction in body weight, fed-state whole blood glucose (WBG), fasting WBG, plasma glucose and plasma cholesterol levels and non-significant reduction in fasting plasma triglyceride levels in ob/ob mice.
Lakshminarayana
N
N
Drug Discovery Division, Glenmark Research Center, Mahape, Navimumbai 400709, India.
Prasad
Y Rajendra
YR
Gharat
Laxmikant
L
Thomas
Abraham
A
Narayanan
Shridhar
S
Raghuram
A
A
Srinivasan
C V
CV
Gopalan
Balasubramanian
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D002784:Cholesterol / Q000097:blood; D055808:Drug Discovery; D005663:Furans / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000737:chemistry; D013379:Substrate Specificity; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002264:Carboxylic Acids; D005663:Furans; D007004:Hypoglycemic Agents; D014280:Triglycerides; D002784:Cholesterol; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C039281:furan