Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia

• Main Authors: M.S. MALAMAS, F.O. ADEBAYO, R.E. MCDEVITT
• Format: Patent
• Language: English
• Published: 15.08.2001
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

This invention provides compounds of Formula (I) having the structure wherein A is (a) or (b); B is carbon or nitrogen; D is oxygen, sulfur, or nitrogen; E is carbon or nitrogen; Y is a bond, methylene, C(O), or CH(OH); R is alkyl containing 1 to 12 carbons, aryl of 6-12 carbon atoms, arylalkyl of 7-15 carbon atoms, halogen, carboxaldehyde, trifluoromethyl, alkoxy of 1-6 carbon atoms, 2,2-dimethyl-1,3-benzodioxole, Het-alkyl wherein the alkyl moiety contains 1-6 carbon atoms, or aryl of 6-10 carbon atoms which is mono-, di-, or tri- substituted with halogen, trifluoromethyl, or alkoxy of 1-6 carbon atoms; Het is (c) (d); G is oxygen, sulfur or nitrogen; R and R are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, trifluoromethyl; R and R are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, trifluoromethyl, alkoxy of 1-6 carbon atoms, nitro, amino, carboalkoxy, carbamide, carbamate, urea, alkylsulfoamide, arylsulfoamide, cycloakyl of 3-8 carbon atoms, -NR (CH2)mCO2H, pyrrolidinone, a heterocyclic ring containing 5 to ring 7 atom rings having 1 to 3 heteroatoms selected from oxygen, nitrogen, or sulfur, or aryl of 6-10 carbon atoms mono-, di-, or tri-substituted with trifluoromethyl, alkyl of 1-6 carbon atoms or, alkoxy of 1-6 carbon atoms; R is hydrogen, alkyl of 1-6 carbon atoms, -CH(R )R , -C(CH2)nCO2R , -C(CH3)2CO2R , -CH(R )(CH2)nCO2R , -CH(R )C6H4CO2R ; R is alkylene of 1 to 3 carbon atoms; R is hydrogen or alkyl of 1 to 6 carbon atoms; R is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-12 carbon atoms, aralkyl of 6-12 carbon atoms, cycloalkyl of 3-8 carbon atoms, phthalic acid, or Q-alkyl wherein the alkyl moiety contains 1-6 carbon atoms; Q is (e), (f), (g), or (h); W is oxygen, sulfur, or nitrogen; R is -CO2R , -CONHR , tetrazole, -PO3R ; R is hydrogen, alkyl of 1-6 carbon atoms, aryl of 7-15 carbon atoms, or aralkyl of 7-15 carbon atoms; R is hydrogen, alkyl, aryl of 6-12 carbon atoms, aralkyl of 7-15 carbon atoms; m = 1-3; n = 1-6; with the proviso that when R is halogen, Y is a bond; or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.