11-ARYL-BENZO[B]NAPHTHO[2,3-D]FURANS AND 11-ARYL-BENZO[B]NAPHTHO[2,3-D]THIOPHENES USEFUL IN THE TREATMENT OF INSULIN RESISTANCE AND HYPERGLYCEMIA

摘要

The invention provides compounds of formula (I) having a structure wherein A is hydrogen, halogen, or OH; B and D are each, independently, hydrogen, halogen, CN, alkyl of 1-6 carbon atoms, aryl, aralkyl of 6-12 carbon atoms, nitro, amino or OR; R is hydrogen, alkyl of 1-6 carbon atoms, -COR1, - CH2CO2R1, -CH(R1a)CO2R1, or -SO2R1; R1 and R1a are each, independently, hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms or aryl; E is S, SO, SO2, O; X is hydrogen, halogen, alkyl of 1-6 carbon atoms, CN, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, aryloxy, arylalkoxy of 6-12 carbon atoms, nitro, amino, alkylsulfanyl of 1-6 carbon atoms, arylsulfanyl, pyridylsulfanyl, 2-N,N-dimethylaminoethylsulfanyl, or - OCH2CO2R1b; R1b is hydrogen or alkyl of 1-6 carbon atoms; Y and Z are each, independently, hydrogen or OR2; R2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, or -CH2CO2R3; R3 is hydrogen or alkyl of 1-6 carbon atoms; C is hydrogen, halogen or OR4; R4 is hydrogen, alkyl of 1-6 carbon atoms, -CH(R5)W, -C(CH3)2CO2R6, 5-thiazolidine-2,4-dione, - CH(R7)CH2CO2R6, -COR6, PO3(R6)2, or -SO2R6; R5 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl, aryl, CH2(1H-imidazol-4-yl), -CH2(3-1H-indolyl), - CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), -CH2CH2(1-oxo-1,3-dihydro- isoindol-2-yl), -CH2(3-pyridyl), or -CH2CO2H; W is -CO2R6, -CONH2, -CONHOH, CN, -CONH(CH2)2CN, 5-tetrazole, -PO3(R6)2, -CH2OH, or -CH2Br, -CONR6CHR7CO2R 8, R6 is hydrogen, alkyl of 1-6 carbon atoms, aryl or aralkyl; R7 is hydrogen, alkyl of 1-6 carbon atoms, aryl or aralkyl; R8 is hydrogen, alkyl of 1-6 carbon atoms, aryl or aralkyl; or a pharmaceutically acceptable salt thereof , which are useful in treating metabolic disorders related to insuling resistance or hyperglycemia.