| 主权项 |
1. A compound of Formula (I) or a pharmaceutically acceptable salt, N-oxide, or isomer thereof: wherein:
L is a bond, —C(R1R2)—, —C(═O)—, or ═C(R1)—;M is a bond, —O—, —S—, —S(O)—, —S(O)2—, or —N(R4)—;m is 0, 1, or 2;n is 0, 1, 2, or 3;p is 1, 2, 3, or 4;Z is —C(═O)—, —C(═S), or —S(O)2—;A is CycA, ArA or HetA, wherein
CycA is an optionally substituted 3-10 membered non-aromatic carbocycle, wherein an optional olefin functionality of the non-aromatic carbocycle is not directly attached to an oxygen, sulfur, or nitrogen substituent;ArA is an aromatic or heteroaromatic ring system optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, bromo, —CN, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, optionally substituted heterocycle, optionally substituted aryl, optionally substituted heteroaryl, —OH, —OR10, and —SR10;HetA is an optionally substituted non-aromatic heterocyclic ring system;each R1 and R2 is independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl, —OH, —OR10, —SR10, and —NR4R5,
or R1 and R2 taken together form an oxo, oxime, or an optionally substituted carbocycle or optionally substituted heterocycle with the carbon to which they are attached;each Rd, R4, and R5 is independently selected from the group consisting of hydrogen, —OH, —CN, optionally substituted C1-C6 alkyl, optionally substituted alkoxyalkyl, optionally substituted hydroxyalkyl, optionally substituted aminoalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, (poly-ethylene-glycol)-ethyl, and an optionally substituted saccharide;
or R4 and R5 taken together form an optionally substituted heterocycle with the nitrogen to which they are attached;each R10 is independently selected from the group consisting of C1-C6 alkyl and optionally substituted C3-C6 cycloalkyl;each Y, provided that Y is not attached directly to a heteroatom of HetA, is selected from the group consisting of:
chloro, bromo, —CN, optionally substituted heteroaryl, —OR10, —SR10, —(CR6R7)vNR4R5, —NR4(CR6R7)vNR4R5, —S(O)0,1,2(CR6R7)vNR4R5, —N(R4)C(O)(CR6R7)vNR4R5, —(CR6R7)vN(R4)C(O)(CR6R7)vNR4R5, —(CR6R7)vNR4(CR6R7)vNR4R5, —NR4(CR6R7)vOR10, —NR4(CR6R7)vS(O)0,1,2R10, —C(O)NR4(CR6R7)vNR4R5, —S(O)0,1,2NR4(CR6R7)vNR4R5, —NR5C(O)NR4(CR6R7)vNR4R5, —OC(O)NR4(CR6R7)vNR4R5, —NR5C(═NR7)NR4(CR6R7)vNR4R5, —N(R4)C(═NR5)R6, —(CR6R7)vN(R4)C(═NR5)R6, —NR4(CR6R7)vN(R4)C(═NR5)R6, —O(CR6R7)vN(R4)C(═NR5)R6, —S(O)0,1,2(CR6R7)vN(R4)C(═NR5)R6, —(CR6R7)vC(═NR5)NR4R5, —NR4(CR6R7)vC(═NR5)NR4R5, —O(CR6R7)vC(═NR5)NR4R5, —S(O)0,1,2 (CR6R7)vC(═NR5)NR4R5, —(CR6R7)vN(R4)C(═NR5)NR4R5, —NR4(CR6R7)vN(R4)C(═NR5)NR4R5, —O(CR6R7)vN(R4)C(═NR5)NR4R5, —S(O)0,1,2 (CR6R7)vN(R4)C(═NR5)NR4R5, —NR4C(═NR5)NR4C(═NR5)NR4R5, —(CR6R7)vC(═NR4)NR5C(═NR4)NR4R5, —NR4(CR6R7)vC(═NR4)NR5C(═NR4)NR4R5, —O(CR6R7)vC(═NR4)NR5C(═NR4)NR4R5, —S(O)0,1,2—(CR6R7)vC(═NR4)NR5C(═NR4)NR4R5, —NR4C(═NR5)NR4R5, —C(═NR4)NR4R5, —C(═NR4)NR4C(O)R6, —NR4SO2R6, —NR4C(O)R6, —NR4C(═O)OR6, —C(O)NR4R5, —(CR6R7)vC(O)NR4R5, —SO2NR4R5, -Heteroaryl-NR4R5, -Heterocyclyl-NR4R5, -Heteroaryl-N(R4)C(═NR5)NR4R5, -Heterocyclyl-N(R4)C(═NR5)NR4R5, —N(R4)—Heteroaryl-NR4R5, —N(R4)—Heterocyclyl-NR4R5, —(CR6R7)vHeteroaryl-NR4R5, —(CR6R7)vHeterocyclyl-NR4R5, —(CR6R7)vHeteroaryl-N(R4)C(═NR5)NR4R5, —(CR6R7)vHeterocyclyl-N(R4)C(═NR5)NR4R5, —(CR6R7)vHeterocyclyl, —O-Heteroaryl, —O-Heterocyclyl, —NR4(CR6R7)vHeteroaryl, —NR4(CR6R7)vHeterocyclyl, —O(CR6R7)vHeteroaryl, —O(CR6R7)vHeterocyclyl, —NR4(CR6R7)vNR5-Heteroaryl, —NR4(CR6R7)vNR5-Heterocyclyl, —O(CR6R7)vNR5-Heteroaryl, —O(CR6R7)vNR5-Heterocyclyl, —O(CR6R7)vO-Heterocyclyl, —NR4R5R9+Q−, —(CR6R7)vNR4R5R9+Q−, —NR4(CR6R7)vNR4R5R9+Q−, —NR4R9+(CR6R7)vNR4R5R9+Q−2, —(CR6R7)v(T)+Q−, and —O(CR6R7)vNR4R5R9+Q−;wherein:
T is pyridin-1-yl, pyrimidin-1-yl, or thiazol-3-yl;Q is a pharmaceutically acceptable counterion;each R6 and R7 are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, optionally substituted C1-C6 alkyl, optionally substituted alkoxyalkyl, optionally substituted hydroxyalkyl, optionally substituted C3-C6 cycloalkyl, —OH, —OR10, —SR10, —NR4R5, —NR4C(O)R5, —C(O)NR4R5, —NR4SO2R5, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;or R6 and R7 taken together form an oxo, oxime, or an optionally substituted carbocycle or an optionally substituted heterocycle with the carbon to which they are attached;R9 is optionally substituted C1-C6 alkyl; andv is 1-4;or two Ys taken together with the carbon atoms to which they are attached form an optionally substituted carbocycle or an optionally substituted heterocycle; oreach Y, in the case where Y is attached directly to a heteroatom of HetA, is selected from the group consisting of:
—(CR6R7)vNR4R5, —S(O)1,2(CR6R7)vNR4R5, —C(O) (CR6R7)vNR4R5, —(CR6R7)wN(R4)C(O)(CR6R7)vNR4R5, —(CR6R7)wNR4(CR6R7)wNR4R5, —NR4(CR6R7)wOR10, —(CR6R7)wS(O)0,1,2R10, —C(O)NR4(CR6R7)wNR4R5, —S(O)1,2NR4(CR6R7)wNR4R5, —C(═NR7)NR4(CR6R7)vNR4R5, —C(═NR5)R6, —(CR6R7)wN(R4)C(═NR5)R6, —S(O)1,2(CR6R7)vN(R4)C(═NR5)R6, —(CR6R7)vC(═NR5)NR4R5, —(CR6R7)wC(═NR5)NR4R5, —S(O)1,2(CR6R7)vC(═NR5)NR4R5, —(CR6R7)wN(R4)C(═NR5)NR4R5, —S(O)1,2(CR6R7)vN(R4)C(═NR5)NR4R5, —C(═NR5)NR4C(═NR5)NR4R5, —(CR6R7)vC(═NR4)NR5C(═NR4)NR4R5, —S(O)1,2—(CR6R7)vC(═NR4)NR5C(═NR4)NR4R5, —C(═NR4)NR4R5, —C(═NR4)NR4C(O)R6, —SO2R6, —C(O)R6, —C(═O)OR6, —C(O)NR4R5, —(CR6R7)vC(O)NR4R5, —SO2NR4R5, -aryl, -heteroaryl, —C(O)N(R4)—Heteroaryl-NR4R5, -Heteroaryl-NR4R5, -Heterocyclyl-NR4R5, -Heteroaryl-N(R4)C(═NR5)NR4R5, -Heterocyclyl-N(R4)C(═NR5)NR4R5, -Heteroaryl-NR4R5, -Heterocyclyl-NR4R5, —(CR6R7)vHeteroaryl-NR4R5, —(CR6R7)vHeterocyclyl-NR4R5, —(CR6R7)vHeteroaryl-N(R4)C(═NR5)NR4R5, —(CR6R7)vHeterocyclyl-N(R4)C(═NR5)NR4R5, —(CR6R7)vHeteroaryl, —(CR6R7)vHeterocyclyl, —(CR6R7)vNR5-Heteroaryl, —(CR6R7)vNR5-Heterocyclyl, —(CR6R7)vO-Heterocyclyl, —R9+Q−, —(CR6R7)wNR4R5R9+Q−, —R9+(CR6R7)vNR4R5R9+Q−2 and —(CR6R7)v(T)+Q;wherein:
T is pyridin-1-yl, pyrimidin-1-yl, or thiazol-3-yl;Q is a pharmaceutically acceptable counterion;each R6 and R7 are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, optionally substituted C1-C6 alkyl, optionally substituted alkoxyalkyl, optionally substituted hydroxyalkyl, optionally substituted C3-C6 cycloalkyl, —OH, —OR10, —SR10, —NR4R5, —NR4C(O)R5, —C(O)NR4R5, —NR4SO2R5, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;or R6 and R7 taken together form an oxo, oxime, or an optionally substituted carbocycle or an optionally substituted heterocycle with the carbon to which they are attached;R9 is optionally substituted C1-C6 alkyl;v is 1-4; andw is 2-4;X is J is a 1-4 atom alkylene or 1-4 atom alkenylene, optionally substituted by one or more substituents selected from the group consisting of Cl, F, CN, CF3, —R19, —OR19, —C(═O)NR19R20, and —C(═O)OR19, wherein said 1-4 atom alkylene or 1-4 atom alkenylene is optionally fused to an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl;R3 is selected from the group consisting of H, R−, —(R30)qOR31, —(R30)qO(R30)qOR31, —R30OC(O)R31, —R30OC(O)OR31, —R30OC(O)NHR31, —R30OC(O)N(R31)2, optionally substituted alkyloxyalkyl, optionally substituted acyloxyalkyl, optionally substituted alkyloxycarbonyloxyalkyl, optionally substituted cycloalkyloxycarbonyloxyalkyl, optionally substituted aryloxycarbonyloxyalkyl, and optionally substituted alkyl-[1,3]dioxol-2-one;each R30 is independently —CH2—, —CH(CH3)—, —C(CH3)2—, or optionally substituted 1,1′-cyclopropylene;R31 is selected from the group consisting of optionally substituted C1-C12 alkyl, optionally substituted C1-C12 alkenyl, optionally substituted C1-C12 alkynyl, C3-C8 cycloalkyl, C3-C5 heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkylcycloalkyl, optionally substituted alkylheterocycloalkyl, optionally substituted alkylaryl, and optionally substituted alkylheteroaryl;each q is independently 2, 3, 4, 5, or 6;R16 is selected from a group consisting of H, —C1-C9alkyl, —C2-C9alkenyl, —C2-C9alkynyl, carbocyclyl, —C1-C9alkylR21, —C2-C9alkenylR21, —C2-C9alkynylR21, carbocyclylR21, —C(═O)OR19, —C1-C9alkylC(═O)OR19, —C2-C9alkenylC(═O)OR19, —C2-C9alkynylC(═O)OR19, carbocyclylC(═O)OR19, or alternatively:
(i) R16 and an R17 are taken together with the atoms to which they are attached to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl, or(ii) R16 and a carbon atom in J are taken together with intervening atoms to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl;each R17 is independently selected from a group consisting of H, halo, —C1-C9alkyl, —C2-C9alkenyl, —C2-C9alkynyl, NR19R20, OR19, C1-C9alkylC(═O)OR19, —C2-C9alkenylC(═O)OR19, —C2-C9alkynylC(═O)OR19, carbocyclylC(═O)OR19, or independently:
(i) R17 and an R18 are taken together with the atoms to which they are attached to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl, or(ii) an R17 and a carbon atom in J are taken together with intervening atoms to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl;each R18 is independently selected from a group consisting of H, halo, —C2-C9alkenyl, —C2-C9alkynyl, NR19R20, OR19, —C1-C9alkylC(═O)OR19, —C2-C9alkenylC(═O)OR19, —C2-C9alkynylC(═O)OR19, carbocyclylC(═O)OR19, or:
(i) a geminal R17 and R18 together form —C2-C9alkenylC(═O)OR19;each R19 is independently selected from a group consisting of H, —C1-C9alkyl, —C2-C9alkenyl, —C2-C9alkynyl, carbocyclyl, —C1-C9alkylR21, —C2-C9alkenylR21, —C2-C9alkynylR21, carbocyclylR21, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;each R20 is independently selected from a group consisting of H, —C1-C9alkyl, —OR19, —CH(═NH), —C(═O)OR19, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;each R21 is independently selected from a group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl; andr is 0 or 1,wherein each —C1-C9alkyl, —C2-C9alkenyl, and —C2-C9alkynyl of R16, R17, R18, R19, R20, and R21 is independently optionally substituted. |
