S1P and/or ATX modulating agents

A compound represented by formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is —O—, —S(O)r—, —CH2—, or —NR—, wherein r is 0, 1, or 2;
• X1, X2, and X5 are each independently CR7 or N;
• X3 is C and is attached by a single bond to -L-, and X4 is CR7 or N, provided that no more than three of X1, X2, X3, X4 or X5 are N;
• Ring A is monocyclic C5-6cycloalkyl or a 5- to 6-membered monocyclic heterocyclyl comprising from 1 to 5 heteroatoms independently selected from N, S, or O;
• wherein Ring A is further optionally substituted with from 1 to 3 R4;
• provided that Ring A is not morpholinyl, thiomorpholinyl or tetrahydro-2H-pyranyl;
• L is a bond, —O—, —NR—, —S(O)r—, —CH2—, or —C(O)—, wherein n is 0, 1, or 2;
• L1 is an C1-8alkylene, C3-8cycloalkylene, —CH2-L2-, or a 3- to 8-membered heterocyclylene comprising 1 to 5 heteroatoms selected from N, S, or O;
• wherein L1 may be optionally substituted with from 1 to 3 independently selected R5;
• L2 is a divalent bridged ring system comprising 6-10 ring members, wherein the ring members may be all carbon atoms or may comprise 1 to 5 heteroatoms selected from N, S, or O;
• R, for each occurrence, is independently hydrogen or C1-8alkyl;
• R1 is a monocyclic C3-8cycloalkyl;
• wherein said C3-8cycloalkyl is substituted with at least one R6 and may be optionally substituted with from 1 to 5 additional R6 substituents, wherein R6 for each occurrence is independently selected;
• R2 is —C(O)OR3, —C(O)N(R3)—S(O)2R3, —S(O)2OR3, —C(O)NHC(O)R3, —Si(O)OH, —B(OH)2, —N(R3)S(O)2R3, —S(O)2N(R3)2, —O—P(O)(OR3)2, or —P(O)(OR3)2, —CN, —S(O)2NHC(O)R3, —C(O)NHS(O)2R3, —C(O)NHOH, —C(O)NHCN, —CH(CF3)OH, —C(CF3)2OH, or a heteroaryl or a heterocyclyl selected from the group consisting of formulae (a)-(i′):
• R3 for each occurrence is independently selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C3-8cycloalkenyl, C6-10aryl, a 5 to 12 membered heteroaryl, and a 3 to 12 membered heterocyclyl;
• wherein the heteroaryl and heterocyclyl independently comprise from 1 to 6 heteroatoms selected from O, N, or S;
• and wherein R3 may be optionally substituted with from 1 to 3 substituents independently selected from the group consisting of halo, C1-4alkoxy, C1-4alkyl, cyano, nitro, hydroxyl, amino, N—C1-4alkylamino, N,N-di-(C1-4alkyl) amino, carbamoyl, N—C1-4alkylcarbamoyl, N,N-di-(C1-4alkyl)carbamoyl, C1-4alkylamido, C1-4alkylsulfonyl, C1-4alkylsulfonamido, sulfamoyl, N—C1-4alkylsulfamoyl, and N,N—(C1-4dialkyl)-sulfamoyl;
• R4 and R5, for each occurrence, are independently halo, hydroxyl, nitro, cyano, C1-8alkyl, C1-8haloalkyl, C1-8alkoxy, C1-4haloalkoxy, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C3-8halocycloalkyl, C3-8cycloalkoxy, C3-8halocycloalkoxy, —NRaRb, —C(O)NRaRb, —N(Ra)C(O)Rb, —C(O)Ra, —S(O)pRa, or —N(Ra)S(O)2Rb, wherein p for each occurrence is independently 0, 1, or 2;
• R6, for each occurrence, is independently halo, hydroxyl, mercapto, nitro, C1-8alkyl, C1-8haloalkyl, C1-8alkoxy, C1-4haloalkoxy, C1-8 alkylthio, C2-8alkenyl, C2-8alkynyl, cyano, —NRaRb, C3-8cycloalkyl, C3-8halocycloalkyl, C6-10aryl, 3- to 8-membered heterocyclyl, or 5- to 6-membered heteroaryl, wherein the heterocyclyl and heteroaryl comprise 1 to 4 heteroatoms independently selected from O, N, or S;
• or two R6 on the same carbon atom together with the carbon to which they are attached form a C3-8spirocycloalkyl;
• R7, for each occurrence, is independently hydrogen, halo, hydroxyl, nitro, cyano, C1-7alkyl, C1-7haloalkyl, C1-7alkoxy, C1-4haloalkoxy, C2-7alkenyl, C2-7alkynyl, C3-8cycloalkyl, C3-8halocycloalkyl, C3-8cycloalkoxy, C3-8halocycloalkoxy, —NRcRd, —C(O)NRcRd, —N(Rc)C(O)Rb, —C(O)Ra, —S(O)pRa, and —N(Rc)S(O)2Rb, wherein p is 0, 1, or 2;
• and
• Ra and Rb, for each occurrence, are independently hydrogen, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C6-10aryl, or C3-8halocycloalkyl.