Phosphorus derivatives as histone deacetylase inhibitors

A compound represented by Formula I:

• Wherein
• Ring A is a 5- to 6- membered heteroaryl or 6-membered aryl;
• With the proviso that Ring A is not tetrahydro-dioxo-pyrimidinyl;
• Ring B is heteroaryl or aryl;
• M is selected from:
• D is a P(O) containing heterocyclyl, wherein the heterocyclyl is optionally substituted with at least one R11;
• R1 and R2 are independently selected from —OR, —NR7R8, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C1-C10 alkenyl, substituted or unsubstituted C1-C10alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, —(CRa2)rR9,
• —ORC(O)OR, —O(CRa2)rR9, —O(CRa2)rC(O)NR7R8, —O(CRa2)r NR7R8, and —O(CRa2)rOR;
• or R1 and R2 together with the phosphorous atom to which they are attached form a phosphorous-containing heterocyclic ring, wherein the heterocyclic ring is optionally substituted with at least one R11;
• or R2 and R6 together with the phosphorous and C atom to which they are respectively attached, form a heterocyclic ring, wherein the heterocyclic ring is optionally substituted with at least one R11;
• or R1 and R4 together with the phosphorous and C atom to which they are respectively attached, form a heterocyclic ring, wherein the heterocyclic ring is optionally substituted with at least one R11;
• R3 is independently selected from hydrogen, —OR, —NR7R8, —NO2, —CN, —C(O)NR7R8, —NR7R8C(O)R, C(O), C1-C7 alkyl, C1-C7 haloalkyl, C1-C7 haloalkyloxy, C1-C7 hydroxyalkyl, C1-C7 alkenyl, C1-C7 alkyl—C(═O)O—, C1-C7 alkyl-C(═O)—, C1-C7 alkynyl, halo, hydroxyalkoxy, C1-C7 alkyl-NHSO2-, C1-C7 alkyl—SO2NH—, C1-C7 alkylsulfonyl, C1-C7 alkylamino and di(C1-C7) alkylamino;
• R4 and R6 are independently of each other hydrogen, —OR, —NR7R8, halo, —CN, —C(O)NR7R8, —NR7R8C(O)R, —C(O)OR, —P(O)(OR)2, oxo, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C4 alkenyl, substituted or unsubstituted C1-C4 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic or substituted or unsubstituted aryl;
• or R4 and R6 together with the C atom to which they are attached form a heterocyclic or carbocyclic ring, which can be optionally substituted with at least one R11;
• R5 is independently selected from hydrogen, OH, NH2, nitro, CN, amide, carboxyl, C1-C7 alkoxy, C1-C7 alkyl, C1-C7 haloalkyl, C1-C7 haloalkyloxy, C1-C7 hydroxyalkyl, C1-C7 alkenyl, C1-C7 alkyl—C(═O)O—, C1-C7 alkyl—C(═O)—, C1-C7 alkynyl, halo, hydroxyalkoxy, C1-C7 alkyl—NHSO2—, C1-C7 alkyl—SO2NH—, C1-C7 alkylsulfonyl, C1-C7 alkylamino, di(C1-C7)alkylamino and L2-R 9,
• R7 and R8 are independently selected from hydrogen, C1-C7 alkyl, —C(O)O—C1—C7alkyl, —P(O)CRa2, —P(O)(OR)2, —(CRa2)rheteroaryl, —(CRa2)rheterocyclic, —(CRa2)r C3-C8 cycloalkyl and —(CRa2)raryl, where alkyl, heteroaryl, heterocyclic, aryl or cycloalkyl is optionally substituted with at least one R11;
• R9 is independently selected from hydrogen, C1-C7 alkyl, heteroaryl, heterocyclic, aryl, and C3-C8 cycloalkyl, where alkyl, heteroaryl, heterocyclic, aryl or cycloalkyl is optionally substituted with at least one R11;
• R11 is independently selected from OH, NH2, nitro, CN, amide, carboxyl, C1-C7 alkoxy, C1-C7 alkyl, C1-C7 haloalkyl, C1-C7 haloalkyloxy, C1-C7 hydroxyalkyl, C1-C7 alkenyl, C1-C7 alkyl-C(═O)O—, C1-C7 alkyl-C(═O)—, C1-C7 alkynyl, halo, hydroxyalkoxy, C1-C7 alkyl—NHSO2—, C1-C 7 alkyl—SO2NH—, C1-C7 alkylsulfonyl, C1-C7 alkylamino and di(C1-C7)alkylamino;
• R is independently H, C1-C7 alkyl, or C3-C10 cycloalkyl, where alkyl or cycloalkyl is optionally substituted with at least one R11;
• Ra is independently selected from H and C1-C7 alkyl, where C1-C7 alkyl is optionally substituted with at least one R11;
• Ll is (CH2)r , ethenyl or cyclopropyl;
• L2 is independently selected from a bond, C1-C4 alkylene, C1-C4 alkynyl, C1-C4 alkenyl, —O—, —S—, —N—, —C(═O)NH—, —NHC(═O)—, —NHC(═O)NH—, —SO2NH—, —NHSO2—, —SO2—, —C(═O)—and —C(═O)O—;
• L3 is a bond, —(CRa2)rC(O)(CRa2)r—, —(CRa2)rO(CRa2)r—, —(CRa2)rC(O)NR7(CRa2)r—, —(CRa2)rNR7C(O)(CRa2)r—, —(CRa2)rNR7C(O)NR7(CRa2)r—, —(CRa2)rOC(O)NR7(CRa2)r—, —(CRa2)r NR7C(O)O(CRa2)r—, —(CRa2)rNR7(CRa2)r —, or —(CR4R6)n—;
• L4 is a bond, —(CRa2)rC(O)(CRa2)r—, —(CRa2)rO(CRa2)r—, —(CRa2)rC(O)NR7(CRa2)r—, —(CRa2)rNR7C(O)(CRa2)r—, —(CRa2)rNR7C(O)NR7(CRa2)r—, —(CRa2)rOC(O)NR7(CRa2)r—, —(CRa2)r NR7C(O)O(CRa2)r—, —(CRa2)rNR7(CRa2)r —, or —(CR4R6)n—;
• X is NH2;
• Z is a bond, heteroaryl, heterocyclic, aryl, or C3-C8 cycloalkyl, where heteroaryl, heterocyclic, aryl or cycloalkyl is optionally substituted with at least one R11;
• n is 0, 1, 2, 3 or 4;
• p is 1, 2, 3 or 4;
• r is independently 0, 1, 2 or 3;
• t is 1, 2, 3, or 4;
• or a stereoisomer or pharmaceutically acceptable salt thereof.