Naphtho[2,3-B]heteroar-4-yl derivatives

A method of treating metabolic disorders mediated by insulin resistance or hyperglycemia in a mammal in need thereof which comprises administering to said mammal, a compound of formula I having the structure ##STR24## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, nitrile, nitro, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, cycloalkylamino of 3-8 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, cycloalkyl of 3-8 carbon atoms, thienyl, furyl, phenyl or phenyl mono-, di-, or tri- substituted with halogen, hydroxy, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or perfluoroalkoxy of 1-6 carbon atoms;

• R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, acyl of 2-7 carbon atoms;
• R.sup.5 is hydrogen, halogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, nitrile, alkoxy of 1-6 carbon atoms, aryloxy, arylalkoxy of 6-12 carbon atoms, arylsulfanyl;
• W is S, O, or NR.sup.9 ;
• R.sup.9 is hydrogen or alkyl of 1-6 carbon atoms,
• X is O, --NR.sup.6 --, or --(CH.sub.2).sub.p NR.sup.6 --;
• R.sup.6 is hydrogen, or alkyl of 1-6 carbon atoms;
• p is 1 to 4;
• Y is methylene, carbonyl, --SO.sub.2 --, or --SO--;
• Z is phenyl, heteroaryl, or naphthyl;
• R.sup.7 and R.sup.8 are each, independently, hydrogen, carboxyl, acyl of 2-7 carbon atoms, hydroxyl, hydroxyalkyl of 1-6 carbon atoms, hydroxyalkanoyl of 1-6 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, aryl of 6-12 carbon atoms, aryloxycarbonyl of 7-13 carbon atoms, heteroaryloxycarbonyl, heteroaryl, tetrazolyl, mercapto, alkylsulfanyl of 1-6 carbon atoms, nitrile, amino, carbamoyl, aminoalkyl of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, --NHSO.sub.2 CF.sub.3, carboxyaldehyde, halogen, nitro, acylamino of 1-6 carbon atoms, 3-hydroxy-cyclobut-3-ene-4-yl-1,2-dione, or tetronic acid, --OCOR.sup.10, --OR.sup.10
• R.sup.10 is aryl of 6-12 carbon atoms, aralkyl of 7-13 carbon atoms, monocyclic or bicyclic heteroaryl or a monocyclic or bicyclic heteroaralkyl, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A method of treating or inhibiting type II diabetes in a mammal in need thereof which comprises administering to said mammal, a compound of formula I having the structure ##STR25## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, nitrile, nitro, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, cycloalkylamino of 3-8 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, cycloalkyl of 3-8 carbon atoms, thienyl, furyl, phenyl or phenyl mono-, di-, or tri- substituted with halogen, hydroxy, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or perfluoroalkoxy of 1-6 carbon atoms;

• R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, acyl of 2-7 carbon atoms;
• R.sup.5 is hydrogen, halogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, nitrile, alkoxy of 1-6 carbon atoms, aryloxy, arylalkoxy of 6-12 carbon atoms, arylsulfanyl;
• W is S, O, or NR.sup.9 ;
• R.sup.9 is hydrogen or alkyl of 1-6 carbon atoms,
• X is O, --NR.sup.6 --, or --(CH.sub.2).sub.p NR.sup.6 --;
• R.sup.6 is hydrogen, or alkyl of 1-6 carbon atoms;
• p is 1 to 4;
• Y is methylene, carbonyl, --SO.sub.2 --, or --SO--;
• Z is phenyl, heteroaryl, or naphthyl;
• R.sup.7 and R.sup.8 are each, independently, hydrogen, carboxyl, acyl of 2-7 carbon atoms, hydroxyl, hydroxyalkyl of 1-6 carbon atoms, hydroxyalkanoyl of 1-6 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, aryl of 6-12 carbon atoms, aryloxycarbonyl of 7-13 carbon atoms, heteroaryloxycarbonyl, heteroaryl, tetrazolyl, mercapto, alkylsulfanyl of 1-6 carbon atoms, nitrile, amino, carbamoyl, aminoalkyl of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, --NHSO.sub.2 CF.sub.3, carboxyaldehyde, halogen, nitro, acylamino of 1-6 carbon atoms, 3-hydroxy-cyclobut-3-ene-4-yl-1,2-dione, or tetronic acid, --OCOR.sup.10, --OR.sup.10
• R.sup.10 is aryl of 6-12 carbon atoms, aralkyl of 7-13 carbon atoms, monocyclic or bicyclic heteroaryl or a monocyclic or bicyclic heteroaralkyl, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A method of modulating glucose levels in a mammal in need thereof which comprises administering to said mammal, a compound of formula I having the structure ##STR26## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, nitrile, nitro, amino, alkylamiino of 1-6 carbon atoms, dialkylarnino of 1-6 carbon atoms per alkyl group, cycloalkylamino of 3-8 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, cycloalkyl of 3-8 carbon atoms, thienyl, furyl, phenyl or phenyl mono-, di-, or tri- substituted with halogen, hydroxy, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or perfluoroalkoxy of 1-6 carbon atoms;

• R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, acyl of 2-7 carbon atoms;
• R.sup.5 is hydrogen, halogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, nitrile, alkoxy of 1-6 carbon atoms, aryloxy, arylalkoxy of 6-12 carbon atoms, arylsulfanyl;
• W is S, O, or NR.sup.9 ;
• R.sup.9 is hydrogen or alkyl of 1-6 carbon atoms,
• X is O, --NR.sup.6 --, or --(CH.sub.2).sub.p NR.sup.6 --;
• R.sup.6 is hydrogen, or alkyl of 1-6 carbon atoms;
• p is 1 to 4;
• Y is methylene, carbonyl, --SO.sub.2 --, or --SO--;
• Z is phenyl, heteroaryl, or naphthyl;
• R.sup.7 and R.sup.8 are each, independently, hydrogen, carboxyl, acyl of 2-7 carbon atoms, hydroxyl, hydroxyalkyl of 1-6 carbon atoms, hydroxyalkanoyl of 1-6 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, aryl of 6-12 carbon atoms, aryloxycarbonyl of 7-13 carbon atoms, heteroaryloxycarbonyl, heteroaryl, tetrazolyl, mercapto, alkylsulfanyl of 1-6 carbon atoms, nitrile, amino, carbamoyl, aminoalkyl of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, --NHSO.sub.2 CF.sub.3, carboxyaldehyde, halogen, nitro, acylamino of 1-6 carbon atoms, 3-hydroxy-cyclobut-3-ene-4-yl-1,2-dione, or tetronic acid, --OCOR.sup.10, --OR.sup.10
• R.sup.10 is aryl of 6-12 carbon atoms, aralkyl of 7-13 carbon atoms, monocyclic or bicyclic heteroaryl or a monocyclic or bicyclic heteroaralkyl, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition which comprises a compound of formula I having the structure ##STR27## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, nitrile, nitro, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, cycloalkylamino of 3-8 carbon atoms, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, halogen, cycloalkyl of 3-8 carbon atoms, thienyl, furyl, phenyl or phenyl mono-, di-, or tri- substituted with halogen, hydroxy, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or perfluoroalkoxy of 1-6 carbon atoms;

• R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, acyl of 2-7 carbon atoms;
• R.sup.5 is hydrogen, halogen, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms, nitrile, alkoxy of 1-6 carbon atoms, aryloxy, arylalkoxy of 6-12 carbon atoms, arylsulfanyl;
• W is S, O, or NR.sup.9 ;
• R.sup.9 is hydrogen or alkyl of 1-6 carbon atoms,
• X is O, --NR.sup.6 --, or --(CH.sub.2).sub.p NR.sup.6 --;
• R.sup.6 is hydrogen, or alkyl of 1-6 carbon atoms;
• p is 1 to 4;
• Y is methylene, carbonyl, --SO.sub.2 --, or --SO--;
• Z is phenyl, heteroaryl, or naphthyl;
• R.sup.7 and R.sup.8 are each, independently, hydrogen, carboxyl, acyl of 2-7 carbon atoms, hydroxyl, hydroxyalkyl of 1-6 carbon atoms, hydroxyalkanoyl of 1-6 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, aryl of 6-12 carbon atoms, aryloxycarbonyl of 7-13 carbon atoms, heteroaryloxycarbonyl, heteroaryl, tetrazolyl, mercapto, alkylsulfanyl of 1-6 carbon atoms, nitrile, amino, carbamoyl, aminoalkyl of 1-6 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, --NHSO.sub.2 CF.sub.3, carboxyaldehyde, halogen, nitro, acylamino of 1-6 carbon atoms, 3-hydroxy-cyclobut-3-ene-4-yl-1,2-dione, or tetronic acid, --OCOR.sup.10, --OR.sup.10
• R.sup.10 is aryl of 6-12 carbon atoms, aralkyl of 7-13 carbon atoms, monocyclic or bicyclic heteroaryl or a monocyclic or bicyclic heteroaralkyl, alkyl of 1-6 carbon atoms, perfluoroalkyl of 1-6 carbon atoms;
• or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.