Sulfonamide derivatives and their use as soluble epoxide hydrolase inhibitors

A compound of Formula I

• or a pharmaceutically acceptable ester, amide, solvate, salt, prodrug, or metabolite thereof, or a salt of such an ester, amide, prodrug, or metabolite, or a solvate of such an ester, amide, salt, prodrug, or metabolite, wherein:
• n is 0 or 1;
• R1 is a cycloalkyl, and the cycloalkyl is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, amino, (mono- or di-C1-C6alkylamino)C0-C4alkyl, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
• R2 is an aryl or heteroaryl, and the aryl and the heteroaryl are unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, cyano, nitro, amino, (mono- or di-C1-C6alkylamino)C0-C4alkyl, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, aryl, —COOR16, —CONR16R16, —SO2NR16R16, —B(OR16)3, —P(═O)(OR16)3, —NHNH2, and triazolyl, wherein each R16 is independently hydrogen or C1-C6 alkyl;
• or
• R2 is —NR11R12 or —N(CH2)x, wherein R11 and R12 are each independently hydrogen, C1-C6alkyl, or cycloalkyl, x is 4 to 6, and any one CH2 in the —N(CH2)x is optionally replaced by NR18, O, S, or SO2, wherein R18 is hydrogen or C1-C6 alkyl, and the cycloalkyl and —N(CH2)x are unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, amino, (mono- or di-C1-C6alkylamino)C0-C4alkyl, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
• X is —OR, —NHR, —SR(R13)m, —SeR(R13)m, —C(R)3, —N(CH2)bSO2R14, —N(CH2)bCOOR14, —N(CH2)bCOR14, —N(CH2)bPOR14, —N(CH2)bBR14, or —N═CR3R4, wherein each R is independently hydrogen, amino, cyano, or C1-C6alkyl with one or more methylene groups optionally replaced by an oxygen, R13 is an oxo group, b is 0 to 6, m is 0, 1, or 2, R14 is hydrogen or C1-C6alkyl, and R3 and R4 are each independently C1-C6alkyl, —SR(R13)m, —SeR(R13)m, —NHR, or R3 and R4 are joined to form a ring optionally containing one additional heteroatom chosen from N, O, and S and the ring is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxyl, cyano, nitro, amino, (mono- or di-C1-C6alkylamino)C0-C4alkyl, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, and C1-C6haloalkoxy;
• and
• Y is O or NR10, wherein R10 is hydrogen or C1-C6alkyl.