Indole and indoline derivatives and methods of use thereof

A compound of formula (I), (II), (III), (IV), (V), or (VI) comprising:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• a is a single or double bond;
• X is CHR6, C═CHR6, or NR6;
• X1 is CHR8 or NR8;
• U, V, W, and Y are each independently —(CH2)p—;
• p at each occurrence is independently 0, 1, or 2;
• Z is —(CH2)q—;
• q is 1, 2, or 3;
• R1, R2, R3, and R4 are each independently hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, -G1, —N(Rb)(R3a), —N(Ra)C(O)R1a, —N(Ra)C(O)O(R1a), —N(Ra)C(O)N(Rb)(R3a), —OR1a, —SR1a, —S(O)2R2a, or haloalkyl;
• wherein
• Ra and Rb, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• R1a and R3a, at each occurrence, are each independently hydrogen, alkyl, haloalkyl, G1, or —(CR6aR7a)n-G1;
• R2a, at each occurrence, is independently alkyl, haloalkyl, G1, or —(CR6aR7a)n-G1;
• n, at each occurrence, is independently 1, 2, 3, 4, or 5;
• R6a and R7a, at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
• G1, at each occurrence, is independently aryl, heteroaryl, heterocycle, or cycloalkyl, wherein each G1 is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, cyano, oxo, —NO2, —OR1b, —OC(O)R1b,—OC(O)N(Rb)(R3b), —SR1b, —S(O)2R2b, —S(O)2N(Rb)(R3b), —C(O)R1b, —C(O)OR1b, —C(O)N(Rb)(R3b), —N(Rb)(R3b), —N(Ra)C(O)R1b, —N(Ra)(O)O(R1b), —N(Ra)C(O)N(Rb)(R3b), —(CR4bR5b)mNO2, —(CR4bR5b)m—OR1b, —(CR4bR5b)m—OC(O)R1b, —(CR4bR5b)m—OC(O)N(Rb)(R3b), —(CR4bR5b)m—SR1b, —(CR4bR5b)m—S(O)2R2b, —(CR4bR5b)m—S(O)2N(Rb)(R3b), —(CR4bR5b)m—C(O)R1b, —(CR4bR5b)m—C(O)OR1b, —(CR4bR5b)m—C(O)N(Rb)(R3b), —(CR4bR5b)m—N(Rb)(R3b), —(CR4bR5b)m—N(Ra)C(O)R1b, —(CR4bR5b)m—N(Ra)C(O)O(R1b), —(CR4bR5b)m—N(Ra)C(O)N(Rb)(R3b), cyanoalkyl, and haloalkyl;
• m, at each occurrence, is independently 1, 2, 3, 4, or 5;
• Ra and Rb, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• R1b and R3b, at each occurrence, are each independently hydrogen, alkoxyalkyl, alkyl, aryl, arylalkyl, haloalkyl, heteroarylalkyl, heterocyclealkyl;
• R2b, at each occurrence, is independently alkyl or haloalkyl;
• R4b and R5b, at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
• R5 is hydrogen, alkyl, -G1, —S(O)2R2a, —S(O)2N(Rb)(R3a), —C(O)R1a, —C(O)OR1a, —C(O)N(Rb)(R3a), —(CR4aR5a)m—NO2, —(CR4aR5a)m—OR1a, —(CR4aR5a)m—OC(O)R1a, —(CR4aR5a)m—OC(O)N(Rb)(R3a), —(CR4aR5a)m—SR1a, —(CR4aR5a)m—S(O)2R2a, —(CR4aR5a)m—S(O)2N(Rb)(R3a), —(CR4aR5a)m—C(O)R1a, —(CR4aR5a)mC(O)OR1a, —(CR4aR5a)m—C(O)N(Rb)(R3a), —(CR4aR5a)m—N(Rb)(R3a), —(CR4aR5a)m—N(Ra)C(O)R1a, —(CR4aR5a)mN(Ra)C(O)O(R1a), —(CR4aR5a)m—N(Ra)C(O)N(Rb)(R3a), —(CR4aR5a)m-G1, cyanoalkyl, or haloalkyl;
• R3a, at each occurrence, is independently hydrogen, alkyl, haloalkyl, G1, or —(CR6aR7a)n-G1;
• R4a and R5a, at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
• R6 is alkyl, —S(O)2R2a, —C(O)R1a, —C(O)OR1a, —C(O)N(Rb)(R3a), —(CR4aR5a)m—NO2, —(CR4aR5a)m—OR1a, —(CR4aR5a)m—OC(O)R1a, —(CR4aR5a)m—OC(O)N(Rb)(R3a), —(CR4aR5a)m—SR1a, —(CR4aR5a)m—S(O)2R2a, —(CR4aR5a)m—S(O)2N(Rb)(R3a), —(CR4aR5a)m—C(O)R1a, —(CR4aR5a)m—C(O)OR1a, —(CR4aR5a)m—C(O)N(Rb)(R3a), —(CR4aR5a)m—N(Rb)(R3a), —(CR4aR5a)m—N(Ra)C(O)R1a, —(CR4aR5a)m—N(Ra)C(O)O(R1a), —(CR4aR5a)m—N(Ra)C(O)N(Rb)(R3a), —(CR4aR5a)m-G1, —(CR4aR5a)m-G2-G1, —CR4a═CR5aS(O)2R2a, —CR4a═CR5a—S(O)2N(Rb)(R3a), —CR4a═CR5a—C(O)R1a, —CR4a═CR5a—C(O)OR1a, —CR4a═CR5a-G1, -G1, -G2-G1, cyanoalkyl, or haloalkyl;
• G2 is aryl, heteroaryl, heterocycle, or cycloalkyl unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, cyano, oxo, —NO2, —OR1b, —OC(O)R1b,—OC(O)N(Rb)(R3b), —SR1b, —S(O)2R2b, —S(O)2N(Rb)(R3b), —C(O)R1b, —C(O)OR1b, —C(O)N(Rb)(R3b), —N(Rb)(R3b), —N(Ra)C(O)R1b, —N(Ra)C(O)O(R1b), —N(Ra)C(O)N(Rb)(R3b), —(CR4bR5b)mNO2, —(CR4bR5b)m—OR1b, —(CR4bR5b)m—OC(O)R1b, —(CR4bR5b)m—OC(O)N(Rb)(R3b), —(CR4bR5b)m—SR1b, —(CR4bR5b)m—S(O)2R2b, —(CR4bR5b)m—S(O)2N(Rb)(R3b), —(CR4bR5b)m—C(O)R1b, —(CR4bR5b)m—C(O)OR1b, —(CR4bR5b)m—C(O)N(Rb)(R3b), —(CR4bR5b)m—N(Rb)(R3b), —(CR4bR5b)m‘—N(Ra)C(O)R1b, —(CR4bR5b)m—N(Ra)C(O)O(R1b), —(CR4bR5b)m—N(Ra)C(O)N(Rb)(R3b), cyanoalkyl, and haloalkyl;
• R7 is hydrogen, alkyl, -G1, —(CR4aR5a)m—NO2, —(CR4aR5a)m—OR1a, —(CR4aR5a)m—OC(O)R1a, —(CR4aR5a)m—OC(O)N(Rb)(R3a), —(CR4aR5a)m—SR1a, —(CR4aR5a)m—S(O)2R2a, —(CR4aR5a)m—S(O)2N(Rb)(R3a), —(CR4aR5a)m—C(O)R1a, —(CR4aR5a)m—C(O)OR1a, —(CR4aR5a)m—C(O)N(Rb)(R3a), —(CR4aR5a)m—N(Rb)(R3a), —(CR4aR5a)m—N(Ra)C(O)R1a, —(CR4aR5a)m—N(Ra)C(O)O(R1a), —(CR4aR5a)m—N(Ra)C(O)N(Rb)(R3a), —(CR4aR5a)m-G1, cyanoalkyl, or haloalkyl;
• and
• R8 is —(CR4aR5a)m-G1, —(CR4aR5a)m-G2-G1, or —CR4a═CR5a-G1;
• with the proviso that in a compound of formula (I),
• when R1, R2 and R4 are each hydrogen;
• R3 is hydrogen or halogen;
• U is CH2;
• V, W, and Y are each —(CH2)p—, wherein p is 0;
• Z is —(CH2)q—, wherein q is 2 or 3;
• X is NR6;
• and
• R6 is alkyl, -G1, or —(CR4aR5a)m-G1, wherein m is 1, R4a and R5a are hydrogen and G1 is phenyl unsubstituted or substituted with alkyl, halogen, hydroxy or —OR1a wherein R1a is alkyl;
• R5 is other than hydrogen, alkyl, —(CR4aR5a)m-G1, —C(O)R1a, —(CR4aR5a)m—OR1a, or —(CR4aR5a)m—C(O)R1a wherein R1a is alkyl, aryl, or heteroaryl, and G1 is aryl or heteroaryl;
• or
• with the proviso that in a compound of formula (IV),
• when a is a double bond;
• V is —(CH2)p—, wherein p is 0;
• Y is —(CH2)p—, wherein p is 2;
• Z is —(CH2)q—, wherein q is 1;
• and
• X is NR6, then
• R6 is other than alkyl, C(O)R1a, —(CR4aR5a)mOR1a, —(CR4aR5a)mC(O)R1a, —(CR4aR5a)m—N(Rb)(R3a), —(CR4aR5a)m-G1, —CR4a═CR5a-G1, -G1, cyanoalkyl or haloalkyl.