Morpholino substituted urea or carbamate derivatives as MTOR inhibitors

A compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein
• m is 1;
• or 2;
• n is 1;
• 2;
• 3;
• or 4;
• Each R1 is independently selected from the group consisting of H;
• halogen;
• CN;
• C(O)OR2;
• OR2a;
• oxo (═O);
• C(O)R2;
• C(O)N(R2R2a);
• S(O)2N(R2R2a);
• S(O)N(R2R2a);
• S(O)2R2;
• S(O)R2;
• N(R2)S(O)2N(R2aR2b);
• N(R2)S(O)N(R2aR2b);
• SR2;
• N(R2R2a);
• NO2;
• OC(O)R2;
• N(R2)C(O)R2a;
• N(R2)S(O)2R2a;
• N(R2)S(O)R2a;
• N(R2)C(O)N(R2aR2b);
• N(R2)C(O)OR2a;
• OC(O)N(R2R2a);
• and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more R3, which are the same or different;
• Optionally two R1 are joined to form together with the ring to which they are attached an 8 to 11 membered heterobicycle, wherein the 8 to 11 membered heterobicycle is a heterocyclic system of two rings with 8 to 11 ring atoms, and wherein at least one ring atom is shared by both rings and that may contain up to the maximum number of double bonds, and wherein at least one ring atom up to 6 ring atoms are replaced by a heteroatom selected from the group consisting of S, —S(O)—, —S(O)2-, O, N, and ═N(O)—, and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom;
• R2, R2a, R2b are independently selected from the group consisting of H;
• C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• R3 is halogen;
• CN;
• C(O)OR4;
• OR4;
• C(O)R4;
• C(O)N(R4R4a);
• S(O)2N(R4R4a);
• S(O)N(R4R4a);
• S(O)2R4;
• S(O)R4;
• N(R4)S(O)2N(R4aR4b);
• N(R4)S(O)N(R4aR4b);
• SR4;
• N(R4R4a);
• NO2;
• OC(O)R4;
• N(R4)C(O)R4a;
• N(R4)S(O)2R4a;
• N(R4)S(O)R4a;
• N(R4)C(O)N(R4aR4b);
• N(R4)C(O)OR4a;
• or OC(O)N(R4R4a);
• R4, R4a, R4b are independently selected from the group consisting of H;
• and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• T0 is phenyl;
• or 5 to 6 membered aromatic heterocycle, wherein the 5 to 6 membered aromatic heterocycle is a heterocycle derived from cyclopentadienyl or benzene, and wherein at least one carbon atom is replaced by a heteroatom selected from the group consisting of S, —S(O)—, —S(O)2-, O, N, and ═N(O)—;
• and wherein T0 is substituted with N(R5a)C(O)N(R5bR5) or N(R5a)C(O)OR5 and optionally further substituted with one or more R6, which are the same or different;
• R6 is halogen;
• CN;
• C(O)OR7;
• OR7;
• C(O)R7;
• C(O)N(R7R7a);
• S(O)2N(R7R7a);
• S(O)N(R7R7a);
• S(O)2R7;
• S(O)R7;
• N(R7)S(O)2N(R7aR7b);
• N(R7)S(O)N(R7aR7b);
• SR7;
• N(R7R7a);
• NO2;
• OC(O)R7;
• N(R7)C(O)R7a;
• N(R7)S(O)2R7a;
• N(R7)S(O)R7a;
• N(R7)C(O)N(R7aR7b);
• N(R7)C(O)OR7a;
• OC(O)N(R7R7a);
• or C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• R5a, R5b, R7, R7a, R7b are independently selected from the group consisting of H;
• C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• R5 is H;
• T2;
• and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more R8, which are the same or different;
• R8 is halogen;
• CN;
• C(O)OR9;
• OR9;
• C(O)R9;
• C(O)N(R9R9a);
• S(O)2N(R9R9a);
• S(O)N(R9R9a);
• S(O)2R9;
• S(O)R9;
• N(R9)S(O)2N(R9aR9b);
• N(R9)S(O)N(R9aR9b);
• SR9;
• N(R9R9a);
• NO2;
• OC(O)R9;
• N(R9)C(O)R9a;
• N(R9)S(O)2R9a;
• N(R9)S(O)R9a;
• N(R9)C(O)N(R9aR9b);
• N(R9)C(O)OR9a;
• OC(O)N(R9R9a);
• or T2;
• R9, R9a, R9b are independently selected from the group consisting of H;
• and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• Optionally R5, R5b are joined to form together with the nitrogen atom to which they are attached an at least the nitrogen atom as ring heteroatom containing 4 to 7 membered heterocyclyl ring, wherein the 4 to 7 membered heterocyclyl ring is a ring with 4, 5, 6 or 7 ring atoms that may contain up to the maximum number of double bonds, and wherein at least one ring atom up to 4 ring atoms are replaced by a heteroatom selected from the group consisting of S, —S(O)—, —S(O)2-, O, N, and ═N(O)—, and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom;
• or 8 to 11 membered heterobicyclyl ring, wherein the 8 to 11 membered heterobicyclyl ring is a heterocyclic system of two rings with 8 to 11 ring atoms, and wherein at least one ring atom is shared by both rings and that may contain up to the maximum number of double bonds, and wherein at least one ring atom up to 6 ring atoms are replaced by a heteroatom selected from the group consisting of S, —S(O)—, —S(O)2-, O, N, and ═N(O)—, and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom, and wherein the 4 to 7 membered heterocyclyl ring;
• and the 8 to 11 membered heterobicyclyl ring are optionally substituted with one or more R10, which are the same or different;
• T2 is C3-7 cycloalkyl;
• 4 to 7 membered heterocyclyl, wherein the 4 to 7 membered heterocyclyl ring is a ring with 4, 5, 6 or 7 ring atoms that may contain up to the maximum number of double bonds, wherein at least one ring atom up to 4 ring atoms are replaced by a heteroatom selected from the group consisting of S, —S(O)—, —S(O)2-, O, N, and ═N(O)—, and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom;
• 8 to 11 membered heterobicyclyl, wherein the 8 to 11 membered heterobicyclyl is a heterocyclic system of two rings with 8 to 11 ring atoms, wherein at least one ring atom is shared by both rings and that may contain up to the maximum number of double bonds, and wherein at least one ring atom up to 6 ring atoms are replaced by a heteroatom selected from the group consisting of S, —S(O)—, —S(O)2-, O, N, and ═N(O)—, and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom;
• phenyl;
• naphthyl;
• indenyl;
• or indanyl, wherein T2 is optionally substituted with one or more R10, which are the same or different;
• R10 is halogen;
• CN;
• C(O)OR11;
• OR11;
• oxo (═O), where the ring is at least partially saturated;
• C(O)R11;
• C(O)N(R11R11a);
• S(O)2N(R11R11a);
• S(O)N(R11R11a);
• S(O)2R11;
• S(O)R11;
• N(R11)S(O)2N(R11aR11b);
• N(R11)S(O)N(R11aR11b);
• SR11;
• N(R11R11a);
• NO2;
• OC(O)R11;
• N(R11)C(O)R11a;
• N(R11)S(O)2R11a;
• N(R11)S(O)R11a;
• N(R11)C(O)N(R11aR11b);
• N(R11)C(O)OR11a;
• OC(O)N(R11R11a);
• or C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more R12, which are the same or different;
• R11, R11a, R11b are independently selected from the group consisting of H;
• C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• R12 is halogen;
• CN;
• C(O)OR13;
• OR13;
• C(O)R13;
• C(O)N(R13R13a);
• S(O)2N(R13R13a);
• S(O)N(R13R13a);
• S(O)2R13;
• S(O)R13;
• N(R13)S(O)2N(R13aR13b);
• N(R13)S(O)N(R13aR13b);
• SR13;
• N(R13R13a);
• NO2;
• OC(O)R13;
• N(R13)C(O)R13a;
• N(R13)S(O)2R13a;
• N(R13)S(O)R13a;
• N(R13)C(O)N(R13aR13b);
• N(R13)C(O)OR13a;
• or OC(O)N(R13R13a);
• R13, R13a, R13b are independently selected from the group consisting of H;
• and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• T1 is phenyl;
• or 5 to 6 membered aromatic heterocycle, wherein T1 is substituted with S(O)N(R14aR14)S(O)2N(R14aR14);
• S(O)R14, S(O)2R14 and optionally further substituted with one or more R15, which are the same or different;
• R15 is halogen;
• CN;
• C(O)OR16;
• OR16;
• C(O)R16;
• C(O)N(R16R16a);
• S(O)2N(R16R16a);
• S(O)N(R16R16a);
• S(O)2R16;
• S(O)R16;
• N(R16)S(O)2N(R16aR16b);
• N(R16)S(O)N(R16aR16b);
• SR16;
• N(R16R16a);
• NO2;
• OC(O)R16;
• N(R16)C(O)R16a;
• N(R16)S(O)2R16a;
• N(R16)S(O)R16a;
• OC(O)N(R16R16a);
• or C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• R14a, R16, R16a, R16b are independently selected from the group consisting of H;
• C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• R14 is C1-6 alkyl, which is optionally substituted with one or more halogen, which are the same or different;
• or an unsubstituted 4 to 7 membered heterocyclyl ring.