Tricyclic Modulators of PP2A

A compound of formula (I):

• wherein:
• X is absent, direct bond, —S—, —(CH2CH2)—, —CH═CH—;
• —O—, —CH2O—, —OCH2—, —C(═O)NRD—, or —N(RD)C(═O)—;
• RD is selected from hydrogen and (C1-C6)alkyl;
• Y is selected from the group consisting of:
• —N(R5)—, —N(R5)—S(O)2—, —CH2—N(R5)—CH2—, —C(R14)(R5)—, —C(═R5a)— and —C(RARB),
• RA and RB together with the C atom to which they are attached form a three to six membered aliphatic carbocycle or a heterocycle which is substituted with Z and attached at the C atom as a spiro ring, and the carbocycle or the heterocycle which is substituted with Z is optionally substituted with one or two substituents selected independently from the group consisting of OH, F, cyano, amino, (C1-C6)alkylamino, (C1-C6)dialkylamino, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, and (C1-C6)alkoxy;
• T is a benzene ring or a five- or six-membered heteroaromatic ring;
• U is a benzene ring or a five- or six-membered heteroaromatic ring;
• R1, R2, R3, and R4 are independently selected from the group consisting of:
• H, halo, —N3, —NR6R7, (C1-C6)alkyl, (C1-C6)haloalkyl, —OR6, —C(O)R6, —OC(O)R6, —C(O)NR6R7, —C(O)OR6, —SR6, —SO2R6, and —SO2NR6R7, —CF3, and —CN, nitro, (C1-C6)haloalkoxy, (C1-C6)haloalkylthio, (C1-C6)haloalkylthio, —CHC(═O)O(C1-C6)alkyl;
• R5 is —(CR15R16)p-Qq-(CR15R16)n-p—Z or
• R5a is ═CR14(CR15R16)p-Qq-(CR15R16)m-p—Z;
• Q is selected from —O—, —NR14′—, —C(O)—, —S—, —S(O)— and —S(O)2—;
• R6 and R7 are independently selected from the group consisting of:
• H and (C1-C6)alkyl;
• R14 is hydrogen or (C1-C6)alkyl;
• R14′ is hydrogen or optionally substituted (C1-C6)alkyl, (C3-C7)cycloalkyl, aryl, or heteroaryl;
• —SO2R8;
• —SO2NR8R9;
• —C(═O)R10;
• —C(═O)OR10;
• or —C(═O)NR8R9;
• wherein said substituents on the (C1-C6)alkyl, (C3-C7)cycloalkyl, aryl, or heteroaryl are selected from the group consisting of hydroxy, halogen, cyano, nitro, amino, (C1-C6)alkylamino, (C1-C6)dialkylamino, (C1-C6)acylamino, (C1-C6)alkylsulfonyl, (C1-C6)alkylthio, (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, and (C1-C6)alkoxy,
• R8 and R9 are independently selected in each instance from hydrogen, (C1-C6)alkyl, aryl, and arylalkyl, wherein said aryl or the aryl of the arylalkyl is optionally substituted with hydroxy, halogen, cyano, nitro, amino, (C1-C6)alkylamino, (C1-C6)dialkylamino, (C1-C6)acylamino, (C1-C6)alkylsulfonyl, (C1-C6)alkylthio, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, or (C1-C6)alkoxy;
• R10 is selected from hydrogen, optionally substituted (C1-C6)alkyl, or optionally substituted aryl, wherein said optional substituents are selected from the group consisting of (C1-C6)alkyl, OR6, NH2, NHMe, N(Me)2, and heterocycle;
• R15 and R16 in each occurrence are selected independently from the group consisting of from H, OH, cyano, amino, (C1-C6)alkylamino, (C1-C6)dialkylamino, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, and (C1-C6)alkoxy, or, taken together, two of R14, R14′, R15 and R16 may form a three to seven membered non-aromatic carbocycle or heterocycle wherein said three to seven membered carbocycle or heterocycle is optionally substituted with one or two substituents selected independently from the group consisting of OH, F, cyano, amino, (C1-C6)alkylamino, (C1-C6)dialkylamino, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, and (C1-C6)alkoxy;
• m is an integer from 1 to 3;
• n is an integer from 2 to 4,
• p is zero, 1 or 2 q is zero or 1:
• with the proviso that when p is 2, m is not 1;
• t is zero, 1 or 2;
• u is zero, 1 or 2:
• v is 1, 2 or 3;
• Z is —NHS((O)(NR18))R17;
• R17 is selected from phenyl and monocyclic heteroaryl, said phenyl and monocyclic heteroaryl optionally substituted with one or two substituents selected independently from the group consisting of OH, halogen, cyano, nitro, amino, (C1-C6)alkylamino, (C1-C6)dialkylamino, (C1-C6)acylamino, (C1-C6)alkylsulfonyl, (C1-C6)alkylthio, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, and (C1-C6)alkoxy, —C(═O)(C1-C6)alkyl, —C(═O)H, (C1-C6)hydroxyalkyl, (C1-C6)haloalkylthio, N3;
• —NR6C(O)OR6′, —OC(O)R6, —C(O)NR6R7, —C(O)OR6, and —SO2NR6R7;
• and R6′ is selected from (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkenyl, (C1-C6)alkynyl or aryl;
• R18 is H or (C1-C6)alkyl, wherein said alkyl is optionally substituted with (C3-C7)cycloalkyl group;
• or an enantiomer, a diastereomer, a tautomer or a pharmaceutically acceptable salt thereof.