Compounds useful for treating gastrointestinal tract disorders

A method for lowering urinary protein excretion in a mammal comprising, administering to the mammal, a compound of formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• Linker is —R13(CHR13)p—[Y—(CH2)r]s—Z—R13—(CH2)t—Z—;
• X is a bond, H, N, O, CR11R12, CR11, C, —NHC(O)NH—, —(CHR13)p— or C3-C6cycloalkyl;
• W is independently, at each occurrence, S(O)2, C(O), or —(CH2)m—;
• Z is independently, at each occurrence, a bond, C(O), or —C(O)NH—;
• Y is independently, at each occurrence, O, S, NH, N(C1-C3alkyl), or —C(O)NH—;
• Q is a bond, NH, —C(O)NH—, —NHC(O)NH—, —NHC(O)N(CH3)—, or —NHC(O)NH—(CHR13);
• m is an integer from 1 to 2;
• n is an integer from 1 to 4;
• r and p are independently, at each occurrence, integers from 0 to 8;
• s is an integer from 0 to 4;
• t is an integer from 0 to 4;
• u is an integer from 0 to 2;
• R1 and R2 are independently H, C1-C6alkyl, C2-C6alkenyl, C4-C8cycloalkenyl, C2-C6alkynyl, C3-C8cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more halogen, OH, CN, —NO2, oxo, —SR9, —OR9, —NHR9, —NR9R10, —S(O)2N(R9)2—, —S(O)2R9, —C(O)R9, —C(O)OR9, —C(O)NR9R10, —NR9S(O)2R10, —S(O)R9, —S(O)NR9R10, —NR8S(O)R9, C1-C6alkyl, C2-C6alkenyl, C4-C8cycloalkenyl, C2-C6alkynyl, C3-C8cycloalkyl, heterocyclyl, heterocycle, aryl, or heteroaryl;
• or
• R1 and R2 together with the nitrogen to which they are attached can form a heterocyclyl or heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O, wherein the heterocyclyl or heteroaryl group is optionally substituted with one or more halogen, OH, CN, —NO2, oxo, —SR9, —OR9, —NHR9, —NR9R10, —S(O)2N(R9)2—, —S(O)2R9, —C(O)R9, —C(O)OR9, —C(O)NR9R10, —NR9S(O)2R10, —S(O)R9, —S(O)NR9R10, —NR9S(O)R10, C1-C6alkyl, C2-C6alkenyl, C4-C8cycloalkenyl, C2-C6alkynyl, C3-C8cycloalkyl, heterocyclyl, heterocycle, aryl, or heteroaryl;
• R3 is CN and R4 is halogen, OH, CN, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, or —C(O)NR9R10;
• R5, R6, R7, and Rs are independently H, halogen, OH, CN, —NO2, C1-C6alkyl, C2-C6alkenyl, C4-C8cycloalkenyl, C2-C6alkynyl, C3-C8cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O, —SR9, —OR9, —NHR9, —NR9R10, —S(O)2N(R9)2—, —S(O)2R9, —C(O)R9, —C(O)OR9, —NR9S(O)2R10, —S(O)R9, —S(O)NR9R10, —NR8S(O)R9;
• R9 and R10 are independently H, C1-C6alkyl, C2-C6alkenyl, C4-C8cycloalkenyl, C2-C6alkynyl, C3-C8cycloalkyl, heterocyclyl, aryl, or heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O
• R11 and R12 are independently H, C1-C6alkyl, OH, NH2, CN, or NO2;
• R13 is independently, at each occurrence, a bond, H, C1-C6alkyl, C4-C8cycloalkenyl, C3-C8cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkenyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R19;
• R14 is independently, at each occurrence, H, C1-C6alkyl, or C1-C6haloalkyl;
• or
• R6 and R14 together with the atoms to which they are attached may combine to form, independently, at each occurrence, 5- to-6 membered heterocyclyl, wherein each C3-C8cycloalkyl, or heterocyclyl is optionally substituted with one or more R19;
• or
• R13 and R14 together with the atoms to which they are attached may combine to form independently, at each occurrence, C3-C8cycloalkyl, heterocyclyl, aryl, or heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O, wherein each heterocyclyl or heteroaryl is optionally substituted with one or more R19;
• R15, R16, R17, and R18 are independently, at each occurrence, H, OH, NH2, or C1-C3alkyl, wherein the alkyl is optionally substituted with one or more R9;
• R19 are independently, at each occurrence, H, OH, NH2, oxo, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy;
• and
• provided that:
• (1) when X is H, n is 1;
• (2) when X is a bond, O, or CR11R12, n is 2;
• (3) when n is 3, X is CR11 or N;
• (4) when n is 4 X is C;
• and
• (5) only one of Q or X is —NHC(O)NH— at the time.