| 主权项 |
1. A compound represented by structural formula (I): or a pharmaceutically acceptable salt thereof, wherein: X is O, S(O)r, NR12, C(O) or CH2; A1 and A2 are each independently CR2 or N; A4 and A5 are each independently CR2, C(R2)2, N, or NR19, one of A3 or A6 is CR2, C(R2)2, N, or NR19, and the other is CR4, provided that at least three of A1, A2, A3, A4, A5, and A6 are independently CR2 or C(R2)2; “------” indicates a double or a single bond; R1 is a C6-20alkyl, a C3-14-carbocyclyl, a 3- to 15-membered heterocyclyl, a C6-10aryl, or a five- to 14-membered heteroaryl, wherein the heterocyclyl and the heteroaryl comprising from 1 to 10 heteroatoms independently selected from N, S or O, and wherein R1 may be optionally substituted with from one to six independently selected R6; R2, for each occurrence, is independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, cyano, carboxy, C1-6alkyl, C1-6haloalkyl, C3-8cycloalkyl, C3-8halocycloalkyl, C1-6alkoxy, C1-6haloalkoxy, C3-8cycloalkoxy, C3-8halocycloalkoxy, C1-6alkanoyl, amino, N—(C1-6alkyl)amino, N,N-di-(C1-6alkyl)amino, C1-6alkoxycarbonyl, C1-6alkanoyloxy, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N-di-(C1-6alkyl)carbamoyl, C1-6alkylamido, mercapto, C1-6alkylthio, C1-6alkylsulfonyl, sulfamoyl, N—(C1-6alkyl)sulfamoyl, N,N-di-(C1-6alkyl)sulfamoyl, and C1-6alkylsulfonamido; R3 is a halo, C1-6haloalkyl or cyano; R4 is a group represented by the following formula: represents the point of attachment; R5 is a C1-6alkyl, C3-8-carbocyclyl, a 3- to 8-membered heterocyclyl, C6-10aryl, a 5- to 10-membered heteroaryl, a bridged ring system comprising from 6 to 12 ring members, a spiro ring system comprising from 5-14 ring members; or a bicyclic ring system represented by the following formula:wherein B′ and B″ are independently selected from the group consisting of monocyclic C3-8-carbocyclyl, a monocyclic 3- to 8-membered heterocyclyl, phenyl or a 5- to 6-membered heteroaryl; wherein R5 may be optionally substituted with from 1 to 4 independently selected R11;
R6, for each occurrence, is independently selected from the group consisting of halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C3-8cycloalkyl, C6-10aryl, C1-6alkoxy-C1-6alkyl, and tri-(C1-6alkyl)silyl; or two R6 that are attached to the same carbon atom may form C3-8-spirocycloalkyl or 3- to 8-membered spiroheterocycloalkyl; R7 is —OH, —C(O)OR15, —C(O)N(R16)2, —C(O)N(R15)—S(O)2R15, —S(O)2OR15, —C(O)NHC(O)R15, —Si(O)OH, —B(OH)2, —N(R15)S(O)2R15, —S(O)2N(R15)2, —O—P(O)(OR15)2, —P(O)(OR15)2, —CN, —S(O)2NHC(O)R15, —C(O)NHS(O)2R15, —C(O)NHOH, —C(O)NHCN, or a heteroaryl or a heterocyclyl selected from the group consisting of formulae (a)-(i′): R8 and R9 are each independently hydrogen, a carboxy, C1-6alkyl, or a C2-6alkenyl; or R8 and R9 together with the carbon to which they are attached are —C(═O)—, a C3-8-spirocycloalkyl, or a 3- to 8-membered spiroheterocycloalkyl; R10 and R12 are each, independently, hydrogen or a C1-6alkyl; R11, for each occurrence, is independently halo, hydroxyl, nitro, cyano, C1-6alkyl, —(CR17CR18)p—R7, C1-6haloalkyl, C1-6alkoxy, C1-4haloalkoxy, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C3-8halocycloalkyl, C3-8cycloalkoxy, C3-8halocycloalkoxy, —NRaRb, —C(O)NRaRb, —N(Ra)C(O)Rb, —C(O)Ra, —S(O)rRa, or —N(Ra)S(O)2Rb; R15 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 14 membered heteroaryl, and a 3 to 15 membered heterocyclyl; wherein the heteroaryl or heterocyclyl comprises from 1 to 10 heteroatoms independently selected from O, N, or S; and wherein R15 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—(C1-4alkyl)amino, N,N-di-(C1-4alkyl)amino, carbamoyl, N—(C1-4alkyl)carbamoyl, N,N-di-(C1-4alkyl)carbamoyl, C1-4alkylamido, C1-4alkylsulfonyl, C1-4alkylsulfonamido, sulfamoyl, N—(C1-4alkyl)sulfamoyl, and N,N—(C1-4dialkyl)-sulfamoyl; R16 is R15; or two R16 together with the nitrogen atom to which they are attached form a 5 to 14 membered heteroaryl or a 3 to 15 membered heterocyclyl, wherein the heteroaryl or heterocyclyl comprises from 1 to 10 heteroatoms independently selected from O, N, or S; and wherein the heteroaryl or heterocyclyl 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—(C1-4alkyl)amino, N,N-di-(C1-4alkyl)amino, carbamoyl, N—(C1-4alkyl)carbamoyl, N,N-di-(C1-4alkyl)carbamoyl, C1-4alkylamido, C1-4alkylsulfonyl, C1-4alkylsulfonamido, sulfamoyl, N—C1-4alkylsulfamoyl, and N,N—(C1-4dialkyl)-sulfamoyl; R17 and R18, for each occurrence, are each independently hydrogen, a halo, or a C1-4haloalkyl; R19 for each occurrence is independently selected from the group consisting of hydrogen, carboxy, C1-6alkyl, C1-6haloalkyl, C3-8cycloalkyl, C3-8halocycloalkyl, C1-6alkanoyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N-di-(C1-6alkyl)carbamoyl, C1-6alkylsulfonyl, sulfamoyl, N—(C1-6alkyl)sulfamoyl, and N,N-di-(C1-6alkyl)sulfamoyl; Ra and Rb, for each occurrence, are independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C6-10aryl, or C3-8halocycloalkyl; Rc is hydrogen or a C1-4alkyl; m is 0 or 1, provided that when m is 0, R5 comprises at least one nitrogen; n is an integer from 1 to 6; p is 0 or an integer from 1 to 6, and r, for each occurrence, is independently 0, 1, or 2, provided that the compound is not 1-(5-fluoro-6-((3-fluorophenyl)sulfonyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-N,N-dimethylmethanamine. |
