4-aryl-1-oxa-9-thia-cylopenta[B]fluorenes

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

• wherein
• B and D are each, independently, hydrogen, halogen, —CN, alkyl of 1-6 carbon atoms, aryl, or aralkyl of 6-12 carbon atoms;
• R1 is —CH(R2)W, or 5-thiazolidine-2,4-dione;
• —CH(R2)W represents a moiety wherein either:
• 1) R2 is selected from —CH2(1H-imidazol-4-yl), —CH2(3-1H-indolyl), —CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), or —CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yl) and W is selected from —CO2R3, —CONH2, —CONHOH, —CN, CONH(CH2)2CN, 5-tetrazole, or —PO3(R3)2;
• or
• 2) R2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, or aryl and W is 5-tetrazole;
• R3 is hydrogen, alkyl of 1-6 carbon atoms, or aryl;
• 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

• wherein
• B and D are each, independently, hydrogen, halogen, —CN, alkyl of 1-6 carbon atoms, aryl, or aralkyl of 6-12 carbon atoms;
• R1 is —CH(R2)W, or 5-thiazolidine-2,4-dione;
• —CH(R2)W represents a moiety wherein either:
• 1) R2 is selected from —CH2(1H-imidazol-4-yl), —CH2(3-1H-indolyl), —CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), or —CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yl) and W is selected from —CO2R3, —CONH2, —CONHOH, —CN, CONH(CH2)2CN, 5-tetrazole, or —PO3(R3)2;
• or
• 2) R2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, or aryl and W is 5-tetrazole;
• R3 is hydrogen, alkyl of 1-6 carbon atoms, or aryl;
• 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

• wherein
• B and D are each, independently, hydrogen, halogen, —CN, alkyl of 1-6 carbon atoms, aryl, or aralkyl of 6-12 carbon atoms;
• R1 is —CH(R2)W, or 5-thiazolidine-2,4-dione;
• —CH(R2)W represents a moiety wherein either:
• 1) R2 is selected from —CH2(1H-imidazol-4-yl), —CH2(3-1H-indolyl), —CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), or —CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yl) and W is selected from —CO2R3, —CONH2, —CONHOH, —CN, CONH(CH2)2CN, 5-tetrazole, or —PO3(R3)2;
• or
• 2) R2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, or aryl and W is 5-tetrazole;
• R3 is hydrogen, alkyl of 1-6 carbon atoms, or aryl;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition which comprises a compound of formula I having the structure

• wherein
• B and D are each, independently, hydrogen, halogen, —CN, alkyl of 1-6 carbon atoms, aryl, or aralkyl of 6-12 carbon atoms;
• R1 is —CH(R2)W, or 5-thiazolidine-2,4-dione;
• —CH(R2)W represents a moiety wherein either:
• 1) R2 is selected from —CH2(1H-imidazol-4-yl), —CH2(3-1H-indolyl), —CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), or —CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yl) and W is selected from —CO2R3, —CONH2, —CONHOH, —CN, CONH(CH2)2CN, 5-tetrazole, or —PO3(R3)2;
• or
• 2) R2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, or aryl and W is 5-tetrazole;
• R3 is hydrogen, alkyl of 1-6 carbon atoms, or aryl;
• or a pharmaceutically acceptable salt thereof.