1, 2-Azole derivatives with hypoglycemic and hypolipidemic activity

A pharmaceutical composition for the prophylaxis or treatment of diabetes, which comprises a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier excipient or diluent.

A pharmaceutical composition for the prophylaxis or treatment of hyperlipidemia, which comprises a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

A pharmaceutical composition for the prophylaxis or treatment of arteriosclerosis, which comprises a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• provided that, when the 1,2-azole ring represented by ring B is isoxazole, ring C is not an optionally substituted pyridone,
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

A pharmaceutical composition for the prophylaxis or treatment of impaired glucose tolerance, which comprises a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

A pharmaceutical composition which is a retinoid-related receptor function regulating agent, which comprises a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

A pharmaceutical composition which is an insulin resistance improving agent, which comprises a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

A method for the prophylaxis or treatment of diabetes in a mammal in need thereof, which comprises administering to the mammal a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof.

A method for making a pharmaceutical composition with hypoglycemic or hypolipidemic activity, said method comprising combining a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is a 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or a hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, for the production of an agent for the prophylaxis or treatment of diabetes.

A pharmaceutical composition which is a GPR40 receptor function modulator comprising a compound represented by the formula

• wherein
• ring A is a ring optionally having 1 to 3 substituents;
• ring B is 1,2-azole ring optionally further having 1 to 3 substituents;
• Xa, Xb and Xc
• are the same or different and each is a bond, —O—, —S—, —SO—, —SO2—, —CO—, —CS—, —CR1(OR2)—, —NR3—, —CONR3— or —NR3CO— (R1 is a hydrogen atom or an optionally substituted hydrocarbon group, R2 is a hydrogen atom or hydroxy-protecting group, and R3 is a hydrogen atom, an optionally substituted hydrocarbon group or an amino-protecting group);
• Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• Yb and Yc
• are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms;
• ring C is a monocyclic aromatic ring optionally further having 1 to 3 substituents;
• and
• R represents —OR4 (R4 is a hydrogen atom or an optionally substituted hydrocarbon group) or —NR5R6 (R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R5 and R6 form, together with the adjacent nitrogen atom, an optionally substituted heterocyclic ring),
• or a salt thereof or a prodrug thereof, and a pharmaceutically acceptable carrier, excipient or diluent.