title: Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents.
abstract: 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.
authors.affiliation: Drug Discovery Division, Glenmark Research Center, Mahape, Navimumbai 400709, India.
authors.forename: N
authors.initials: N
authors.lastname: Lakshminarayana
authors.forename: Y Rajendra
authors.initials: YR
authors.lastname: Prasad
authors.forename: Laxmikant
authors.initials: L
authors.lastname: Gharat
authors.forename: Abraham
authors.initials: A
authors.lastname: Thomas
authors.forename: Shridhar
authors.initials: S
authors.lastname: Narayanan
authors.forename: A
authors.initials: A
authors.lastname: Raghuram
authors.forename: C V
authors.initials: CV
authors.lastname: Srinivasan
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Gopalan
mesh_terms: 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
chemical_list: 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