Substituted phenothiazines as ferroptosis inhibitors

A compound of formula (I) or a stereoisomer or tautomer thereof,

• wherein,
• R1 is selected from hydrogen, amino, —NR6R7, halo, —C(O)NH(CR8R9)tR10, —C(O)R11, —CR12R13NH(CR14R15)wR16, —COOR11, —S(O)2R11, —SO2NR6R7, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl;
• wherein said cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl can be unsubstituted or substituted with one or more Z1;
• wherein t is an integer selected from 0, 1, 2, 3 or 4;
• wherein w is an integer selected from 0, 1, 2, 3 or 4;
• R2 is selected from hydrogen, amino, —NR6R7, halo, C(O)NH(CR8R9)nR10, —C(O)R11, —CR12R13NH(CR14R15)mR16, —COOR11, —S(O)2R11, —SO2NR6R7, cycloalkyl, aryl, heterocyclyl, and heteroaryl;
• wherein said cycloalkyl, aryl, heterocyclyl, or heteroaryl can be unsubstituted or substituted with one or more Z2;
• wherein n is an integer selected from 0, 1, 2, 3 or 4;
• wherein m is an integer selected from 0, 1, 2, 3 or 4;
• R3 is selected from hydrogen, amino, —NR6R7, halo, NO2, —C(O)NH(CR8R9)pR10, —C(O)R11, —CR12R13NH(CR14R15)qR16, —COOR11, —S(O)2R11, and —SO2NR6R7, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl;
• wherein said cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl can be unsubstituted or substituted with one or more Z3;
• wherein p is an integer selected from 0, 1, 2, 3 or 4;
• wherein q is an integer selected from 0, 1, 2, 3 or 4;
• R4 is selected from hydrogen, amino, —NR6R7, halo, NO2, —C(O)NH(CR8R9)yR10, —C(O)R11, —CR12R13NH(CR14R15)zR16, —COOR11, —S(O)2R11, and —SO2NR6R7, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl;
• wherein said cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl can be unsubstituted or substituted with one or more Z4;
• wherein y is an integer selected from 0, 1, 2, 3 or 4;
• wherein z is an integer selected from 0, 1, 2, 3 or 4;
• wherein at least one of R1 to R4 is not hydrogen;
• each R6 and R7 is independently selected from hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl;
• wherein said alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl can be unsubstituted or substituted with one or more Z1a;
• each R8, R9, R12, R13, R14 and R15 is selected from hydrogen, halogen, hydroxyl, amino, alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl;
• wherein said alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl can be unsubstituted or substituted with one or more Z1b;
• each R10, R11 and R16 is selected from heterocyclyl, —NR6R7, alkyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl;
• wherein said heterocyclyl, alkyl, cycloalkyl, aryl, arylalkyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl can be unsubstituted or substituted with one or more Z1c;
• each R17 is independently selected from to alkyl, aryl, cycloalkyl, arylalkyl, heterocyclyl, heteroaryl;
• each R18 and R19 is independently selected from hydrogen, alkyl, aryl, cycloalkyl, arylalkyl, heterocyclyl, heteroaryl;
• each Z1, Z2, Z3, Z4, Z1a, and Z1b is independently selected from halo, haloalkyl, alkyl, haloalkyloxy, cycloalkyl, aryl, alkylaryl, heterocyclyl, heteroaryl, hydroxyl, —OR17, cyano, amino, —NR17R18, —C(O)2R18, —C(O)NR18R19, —C(O)R17, —S(O)R18, —S(O)2R18, —S(O)2NR18R19, nitro;
• each Z1c is independently selected from u halo, haloalkyl, alkyl, haloalkyloxy, cycloalkyl, aryl, alkylaryl, heterocyclyl, heteroaryl, hydroxyl, —OR17, cyano, amino, —NR17R18, —C(O)2R18, —C(O)NR18R19, —S(O)R18, —S(O)2R18, —S(O)2NR18R19 nitro;
• wherein when R1 is
• then R3 is not H, Cl or —C(O)R11;
• or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof;
• with the proviso that said compound is not