Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia

The prevalence of insulin resistance in glucose intolerant subjects has long been recognized. Reaven et al ( 1976, 60, 80) used a continuous infusion of glucose and insulin (insulin/glucose clamp technique) and oral glucose tolerance tests to demonstrate that insulin resistance existed in a diverse group of nonobese, nonketotic subjects. These subjects ranged from borderline glucose tolerant to overt, fasting hyperglyceriaa. The diabetic groups in these studies included both insulin dependent (EDDM) and noninsulin dependent (NIEDDM) subjects. This invention provides compounds of Formula I having the structure whereinRand Rare each, independently, hydrogen, alkyl of 1-6 carbon atoms, halogen, perfluoroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, thienyl, furyl, phenyl or phenyl substituted with trifluoromethyl, chloro, methoxy, or trifluoromethoxy;Rand Rare each, independently, hydrogen, carboxyl, hydroxyl, hydoxyalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, perfluoroalkoxy of 1-6 carbon atoms, alkanoyloxy of 2-7 carbon atoms, perfluoroalkanoyloxy of 2-7 carbon atoms, arylalkoxy of 7-15 carbon atoms, aryloxy of 6-12 carbon atoms, aroyloxy of 6-12 carbon atoms, aryloxycarbonyl of 7-13 carbon atoms, alkoxycarbonyl of 2-7 carbon atoms, perfluoroalkoxycarbonyl of 2-7 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamnino of 1-6 carbon atoms per alkyl group, tetrazolyl, mercapto, nitrile, nitro, amino, -NHSOCF, carbamoyl, carboxyaldehyde, halogen, acylamino, 3-hydroxy-cyclobut-3-ene-4-yl-1,2-dione, pyridyl, isoxazolyl, pyrimidyl or pyrimidyl substituted with mercapto, or tetronic acid;Ris hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, naphthalenylmethyl, benzyl or benzyl substituted with halogen,Rand Rare each, independently, hydrogen, alkyl of 1-6 carbon atoms, or perfluoroalkyl of 1-6 carbon atoms, or Rand Rmay be taken together as a diene unit having the structure -CH CH-CH CH-;W is S or O,X is -NRCH-, -NR-, or O;Ris hydrogen or alkyl;Y is carbonyl, methylene, ethyl, or -NHCH-;Z is phenyl, pyridyl, naphthyl, thienyl, furyl, pyrrolyl, pyrazolyl, isoxazolyl, or isothiazolyl;or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.