Phenoxy carboxylic acid compounds and medical uses thereof

A method for prevention or treatment of a disease associated with PPARα and/or PPARγ in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound represented by Formula (Ia), its pharmaceutically acceptable salt or ester, prodrug, stereoisomer, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof,

• wherein,
• R1 and R2 are each independently C1-C4 alkyl or C1-C4 alkoxy, and the C1-C4 alkyl or C1-C4 alkoxy is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R3 is halogen;
• R4 is hydrogen, halogen, nitro, hydroxyl, C1-C4 alkyl or C1-C4 alkoxy, wherein the C1-C4 alkyl is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R5 and R6 are each independently C1-C4 alkyl;
• R7 is —C(O)X or cyano;
• wherein X is hydroxyl or C1-C4 alkoxy;
• n is 1, 2, 3 or 4.

A method for reducing body weight, reducing body fat, reducing a liver fat fraction, preventing or treating obesity, and/or preventing or treating non-alcoholic fatty liver disease (NAFLD) in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound represented by Formula (Ia), its pharmaceutically acceptable salt or ester, prodrug, stereoisomer, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof,

• wherein,
• R1 and R2 are each independently C1-C4 alkyl or C1-C4 alkoxy, and the C1-C4 alkyl or C1-C4 alkoxy is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R3 is halogen;
• R4 is hydrogen, halogen, nitro, hydroxyl, C1-C4 alkyl or C1-C4 alkoxy, wherein the C1-C4 alkyl is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R5 and R6 are each independently C1-C4 alkyl;
• R7 is —C(O)X or cyano;
• wherein X is hydroxyl or C1-C4 alkoxy;
• n is 1, 2, 3 or 4.

A method for reducing a blood glucose level, increasing insulin sensitivity, preventing or treating insulin resistance, and/or preventing or treating diabetes mellitus in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound represented by Formula (Ia), its pharmaceutically acceptable salt or ester, prodrug, stereoisomer, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof,

• wherein,
• R1 and R2 are each independently C1-C4 alkyl or C1-C4 alkoxy, and the C1-C4 alkyl or C1-C4 alkoxy is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R3 is halogen;
• R4 is hydrogen, halogen, nitro, hydroxyl, C1-C4 alkyl or C1-C4 alkoxy, wherein the C1-C4 alkyl is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R5 and R6 are each independently C1-C4 alkyl;
• R7 is —C(O)X or cyano;
• wherein X is hydroxyl or C1-C4 alkoxy;
• n is 1, 2, 3 or 4.

A method for lowering a blood total cholesterol level, lowering a blood triglyceride level, lowering a blood low-density lipoprotein level, and/or increasing a blood high-density lipoprotein level in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound represented by Formula (Ia), its pharmaceutically acceptable salt or ester, prodrug, stereoisomer, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof,

• wherein,
• R1 and R2 are each independently C1-C4 alkyl or C1-C4 alkoxy, and the C1-C4 alkyl or C1-C4 alkoxy is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R3 is halogen;
• R4 is hydrogen, halogen, nitro, hydroxyl, C1-C4 alkyl or C1-C4 alkoxy, wherein the C1-C4 alkyl is optionally substituted with one or several substituents independently selected from halogen and hydroxyl;
• R5 and R6 are each independently C1-C4 alkyl;
• R7 is —C(O)X or cyano;
• wherein X is hydroxyl or C1-C4 alkoxy;
• n is 1, 2, 3 or 4.