Spirocyclic compounds

A compound selected from:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• A is selected from the group consisting of CH2 and NH;
• X1a is selected from aryl and aryl substituted by R2a;
• X1b is selected from aryl and aryl substituted by R2b;
• X1c is selected from the group consisting of aryl and aryl substituted with R2c;
• X1d is selected from the group consisting of aryl and aryl substituted with R2d;
• X2a is selected from the group consisting of heterocyclyl, heterocyclyl substituted by R3, heteroaryl, heteroaryl substituted by R4, and C1-6-alkyl;
• X3a is selected from the group consisting of hydrogen, heterocyclyl, heterocyclyl substituted by R3, heteroaryl, heteroaryl substituted by R4, and C1-6-alkyl;
• X4a is selected from the group consisting of hydrogen, aryl, aryl substituted by R2, heterocyclyl, heterocyclyl substituted by R3, heteroaryl, heteroaryl substituted by R4, and C1-6-alkyl;
• X5a is aryl substituted by R6a;
• X6a is aryl substituted with —C(═O)—OH;
• X7a is selected from the group consisting of heteroaryl and heteroaryl substituted by R7;
• X8a is heteroaryl substituted by R7a;
• XB is selected from the group consisting of:
• aryl;
• aryl substituted by R6;
• heteroaryl;
• and
• heteroaryl substituted by R7;
• YB is absent or —C(═O)—;
• R1 is absent or =0;
• R2 is selected from the group consisting of:
• —C(═O)—O—C1-6-alkyl;
• —NH—C(═O)—C1-6-alkyl;
• —NH2;
• —OH;
• and —NO2;
• R2a is selected from the group consisting of:
• —C(═O)—O—C1-6-alkyl;
• —NH—C(═O)—C1-6-alkyl;
• —NH2;
• —OH;
• and —NO2;
• R2b is selected from the group consisting of:
• —C(═O)—O—C1-6-alkyl;
• —NH—C(═O)—C1-6-alkyl;
• —NH2;
• and —NO2;
• R2e is selected from the group consisting of:
• —C(═O)—O—C1-6-alkyl;
• —NH—C(═O)—C1-6-alkyl;
• and —NO2;
• R2d is selected from the group consisting of:
• —C(═O)—O—C1-6-alkyl;
• —NH—C(═O)—C1-6-alkyl;
• and —NO2;
• R3 is selected from the group consisting of —C(═O)—C1-6-alkyl and =0;
• R4 is selected from the group consisting of —C(═O)—O—C1-6-alkyl;
• C1-6alkyl;
• —NH2;
• —NH—C(═O)—C1-6-alkyl;
• and —NO2;
• R5 is C1-6-alkyl;
• R6 is selected from the group consisting of:
• —C(═O)—OH;
• —NH—C(═O)—C1-6-alkyl;
• —NH2;
• and
• —NO2;
• R6a is selected from the group consisting of:
• —C(═O)—OH;
• —NH—C(═O)—C1-6-alkyl;
• and
• —NO2;
• R7 is selected from the group consisting of:
• —C(═O)—OH;
• —C(═O)—O—C1-6-alkyl;
• —NH2;
• and
• —NO2;
• and
• R7a is selected from the group consisting of —C(═O)—OH and —C(═O)—O—C1-6-alkyl;
• XB1 is selected from the group consisting of arylene and heteroarylene;
• “Tail” is
• X1 is selected from bond, NR34, CH2, CHR34, C(R34)2, O, and S;
• X22 is selected from halo, —NH2, —NHR34, —N(R34)2, hydroxyl, thiol, —B(OH)2, —Sn(R36)3, —Si(R36)3, —OS(O)2alkyl, —OS(O)2haloalkyl, alkenyl, alkynyl, ethynyl, ethenyl, —C(O)H, —NR34C(O)alkene, —NR34C(O)alkyne, cyano, —SC(O)alkyl, OC(O)alkyl, heterocycle, —C(O)OH, hydrogen, alkyl, aryl, heteroaryl, aliphatic, heteroaliphatic, and carbocyclic;
• R34 and R34′ are independently selected at each occurrence from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6heterocycle, aryl, heteroaryl, —(CO)R36, —(CS)R36, —(C═NH)R36, —(SO)R36, and —(SO2)R36;
• R36 is independently selected at each occurrence from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, C3-C6heterocycle, aryl, heteroaryl, hydroxyl, C1-C6alkoxy, thio, C1-C6thioalkyl, —NH2, —NH(C1-C6alkyl, C3-C7cycloalkyl, C3-C7heterocycle, aryl, or heteroaryl), and —N(independently C1-C6alkyl, C3-C7cycloalkyl, C3-C7heterocycle, aryl, or heteroaryl)2;
• R20, R21, R22, R23, and R24 are independently selected from bond, alkyl, —C(O)—, —C(O)O—, —OC(O)—, —C(O)alkyl, —C(O)Oalkyl, —C(S)—, —SO2—, —S(O)—, —C(S)—, —C(O)NH—, —NHC(O)—, —N(alkyl)C(O)—, —C(O)N(alkyl)-, —O—, —S—, —NH—, —N(alkyl)-, —CH(—O—R26)—, —CH(—NR34R34′)—, —C(—O—R26)alkyl-, —C(—NR34R34′)alkyl-, —C(R4OR40)—, -alkyl(R27)-alkyl(R28)—, —C(R27R28)—, —P(O)(OR26)O—, —P(O)(OR26)—, —NR34C(O)NR34′—, alkene, haloalkyl, alkoxy, alkyneheteroarylalkyl, aryl, arylalkyl, heterocycle, aliphatic, heteroaliphatic, heteroaryl, lactic acid, glycolic acid, carbocycle, -(ethylene glycol)1-6-, -(lactic-co-glycolic acid)1-6-, -(propylene glycol)1-6-, —O—(CH2)1-12—O—, —NH—(CH2)1-12—NH—, —NH—(CH2)1-12—O—, —O—(CH2)1-12—NH—, —S—(CH2)1-12—O—, —O—(CH2)1-12—S—, —S—(CH2)1-12—S—, —S—(CH2)1-12—NH—, and —NH—(CH2)1-12—S—;
• each of which R20, R21, R22, R23, and R24 is optionally substituted with one or more substituents selected from R101;
• wherein at least one of R20, R21, R22, R23, and R24 is not a bond;
• R101 is independently selected at each occurrence from hydrogen, alkyl, alkene, alkyne, haloalkyl, alkoxy, hydroxyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocycloalkyl, aryloxy, heteroaryloxy, CN, —COOalkyl, COOH, NO2, F, Cl, Br, I, CF3, NH2, NHalkyl, N(alkyl)2, aliphatic, and heteroaliphatic;
• R26 is selected from hydrogen, alkyl, silane, arylalkyl, heteroarylalkyl, alkene, alkyne, aryl, heteroaryl, heterocyclic, aliphatic and heteroaliphatic;
• R27 and R28 are independently selected from hydrogen, alkyl, amine, or together with the carbon atom to which they are attached, form C(O), C(S), C═CH2, a C3-C6 spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O, or form a 1 or 2 carbon bridged ring;
• and
• R40 is selected at each instance from:
• hydrogen, alkyl, alkene, alkyne, halogen, hydroxyl, alkoxy, azide, amino, cyano, —NH(aliphatic), —N(aliphatic)2, —NHSO2(aliphatic), —N(aliphatic)SO2alkyl, —NHSO2(aryl, heteroaryl or heterocyclic), —N(alkyl)SO2(aryl, heteroaryl or heterocyclic) —NHSO2alkenyl, —N(alkyl)SO2alkenyl, —NHSO2alkynyl, —N(alkyl)SO2alkynyl, haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl, heteroalkyl, heterocyclic, and carbocyclic.