Modulators of 5-ht receptors and methods of use thereof

A compound of formula (I):

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• A is selected from the group consisting of
• R1, R3, R4, and R5 are independently selected from the group consisting of hydrogen, alkenyl, alkyl, haloalkyl, G1, G2, —(CR4aR5a)m-G1, and —(CR4aR5a)m-G2;
• R4a and R5a, at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
• G1, at each occurrence, is independently aryl or heteroaryl, 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, —NO2, —OR1b, —OC(O)R1b, —OC(O)N(Rb)(R3b), —SR1b, —S(O)R2b, —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)m—NO2, —N(Rb)S(O)2(R2b), —(CR4bR5b)m—OR1b, —C(OH)[(CR4bR5b)m—R4b]2, —(CR4bR5b)m—OC(O)R1b, —(CR4bRb)m—OC(O)N(Rb)(R3b), —(CR4bR5b)m—SR1b, —(CR4bR5b)m—S(O)R2b, —(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)Rb, —(CR4bR5b)m—N(Ra)C(O)O(R1b), —(CR4bR5b)m—N(Ra)C(O)N(Rb)(R3b), —(CR4bR5b)m—N(Rb)S(O)2(R2b), cyanoalkyl, and haloalkyl;
• G2 is cycloalkyl, cycloalkenyl, or heterocycle unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, cyano, oxo, —SR1b, —S(O)R2b, —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)m—NO2, —N(Rb)S(O)2(R2b), —(CR4bR5b)m—OR1b, —(CR4bR5b)m—OC(O)R1b, —(CR4bR5b)m—OC(O)N(Rb)(R3b), —(CR4bR5b)m—SR1b, —(CR4bR5b)m—S(O)R2b, —(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)(Rb), —(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), —(CR4bR5b)m—N(Rb)S(O)2(R2b), cyanoalkyl, and haloalkyl;
• Ra and Rb, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• R1b and R3b, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• R2b, at each occurrence, is independently alkyl or haloalkyl;
• R4b and R5b, at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
• m, at each occurrence, is independently 1, 2, 3, 4, or 5;
• R2 is selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, haloalkyl, —(CR4aR5a)m-G1, —(CR4aR5a)p—O-G1, —C(O)-G1, —(CR4aR5a)m-G2, —(CR4aR5a)p—O-G2, —C(O)-G2, —S(O)2R6, and —C(O)NR7R8;
• p, at each occurrence, is independently 2, 3, 4, or 5;
• R6 and R7 are independently selected from the group consisting of alkyl, haloalkyl, G1, —(CR4aR5a)m-G1, G2 and —(CR4aR5a)m-G2;
• R8 is selected from the group consisting of hydrogen, alkyl, and haloalkyl;
• or
• R7 and R8 taken together with the nitrogen to which they are attached form a heterocycle;
• X1 is N or CR9;
• X2 is N or CR10;
• X3 is N or CR11;
• X4 is N or CR12;
• provided that only one or two of X1, X2, X3, or X4 can be N;
• R9, R10, R11, R12, R13, R14, R15 and R16 are each independently hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, -G1, -G2, —NO2, —OR1a, —OC(O)R1a, —OC(O)N(Rb)(R3a), —SR1a, —S(O)R2a, —S(O)2R2a, —S(O)2N(Rb)(R3a), —C(O)R1a, —C(O)G3, —C(O)OR1a, —C(O)N(Rb)(R3a), N(Rb)(R3a), —N(Ra)C(O)R1a, —N(Ra)C(O)O(R1a), —N(Ra)C(O)N(Rb)(R3a), —N(Ra)S(O)2(R2a), —(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)R2a, —(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, —CR4a═CR5a-G1, —(CR4aR5a)m-G2, —CR4a═CR5a-G2, —CR6a═C(R7a)2, cyanoalkyl, haloalkyl, (v), (vi), (vii) or (vi);
• wherein
• R1a and R3a, at each occurrence, are each independently hydrogen, alkyl, haloalkyl, G1, —(CR4aR5a)m-G1, G2, or —(CR4aR5a)m-G2;
• R2a, at each occurrence, is independently alkyl, haloalkyl, G1, or —(CR4aR5a)m-G1;
• R6a is alkyl or haloalkyl;
• R7a, at each occurrence, is independently hydrogen, alkyl, or haloalkyl;
• G3 is a heterocyclic ring attached to the adjacent carbonyl moiety through a nitrogen atom contained within the heterocycle;
• q is 1 or 2;
• or
• R9 and R10, R10 and R11, R11 and R12, or R13 and R14 taken together with the carbon atoms to which they are attached form a substituted or unsubstituted phenyl, cycloalkyl, heterocycle, or heteroaryl ring;
• Y1 is NR17, CR18R19, C(O), S(O)n, or O;
• Y2 is NR20, CR18R19, C(O), or S(O)n;
• Y3 is NR17, CR18R19, C(O), or S(O)n;
• or
• Y1 and Y2 together are CR18═CR19, provided Y3 is other than NR17;
• or
• Y2 and Y3 together are CR18═CR19, provided Y is other than NR17 or O;
• n is 1 or 2;
• provided that only one of Y and Y3 can be NR17;
• or Y1 and Y3 are other than NR17 when Y2 is NR20;
• or only one of Y1, Y2, or Y3 can be C(O) or S(O)n;
• or Y2 is other than NR20 or S(O)n when Y1 is O;
• or Y3 is other than NR17 when Y1 is O;
• R17 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, haloalkyl, —C(O)-G1, —(CR4aR5a)m-G1, —C(O)-G2, and —(CR4aR5a)m-G2;
• R18 and R19 are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
• and
• R20 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, haloalkyl, —C(O)-G1, —C(O)NRa-G1, —S(O)n-G1, —(CR4aR5a)m-G1, —C(O)-G2, —C(O)NRa-G2, —S(O)n-G2, and —(CR4aR5a)m-G2.