Substituted phenoxybenzamides

A compound of general formula (I):

• in which:
• R1 and R2 are the same or different and are independently a hydrogen atom, a halogen atom, a C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, or —CN group, in which at least one of R1 and R2 is a halogen atom;
• R3 is, in each occurrence, independently, a halogen atom, a C1-C4-alkyl or —CN group;
• q is an integer of 0, 1, 2, or 3;
• R4 is a hydrogen atom or a C1-C6-alkyl group;
• R5 is a —C(═O)R7, —C(═O)OR7, —C(═O)N(R7)(R8), —NHC(═O)R7, —S(═O)2R7, —NHS(═O)2R7, —S(═O)2NR7R8, —NO2, —CN, or a
• in which:
• each of Z1, Z2, Z3 and Z4 is independently —CH—, —C(C1-C6-alkyl)-, —C(═O)—, —S—, —O—, —N— or —NH, such that at least one of Z1, Z2, Z3 and Z4 is —N— or —NH—;
• X is —O—, —NH—, —N(C1-C6-alkyl)-, —S—, —S(═O)2—, —C(═O)—, —C(═O)O—, or —C(═O)NH—;
• R6 is —(CR152)n—(CR15(OR11))—(CR152)m—R9, or —(CH2)n—Y;
• Y is:
• a) an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, said aryl, heteroaryl, cycloalkyl or heterocycloalkyl group being substituted with one or more —(CH2)oY′ groups, in each occurrence of said —(CH2)oY′ group:
• o is an integer of 0;
• and
• Y′ is, independently:
• a C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxyalkyl, cycloalkyl, or heterocycloalkyl group,
• or
• an —ORc′ group, in each occurrence of which, Rc′ is, independently:
• a —C(═O)Re group, in which Re is defined infra, or
• an —S(═O)2Re group, in which Re is defined infra, or
• a C1-C6-haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, in which C1-C6-haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, are, independently of each other, optionally substituted one or more times with:
• a halogen atom, or
• an —OH, or
• an aryl group, or
• an —ORf group, in which Rf is as defined infra, or
• an —NRd1Rd2 group, in which Rd1 and Rd2 are as defined infra, or
• a —OP(═O)(ORf)2 group, in which Rf is as defined infra;
• or
• an —NRd1Rd2 group, as defined infra, with the provisos that:
• when one of Rd1 and Rd2 is H, then the other of Rd1 and Rd2 is neither H nor C1-C6-alkyl, and
• Rd1 and Rd2 cannot simultaneously be C1-C6-alkyl;
• or
• an —NRaS(═O)2Rb group, as defined infra, with the proviso that:
• when Ra is H, then Rb is not C1-C6-alkyl;
• Or
• an —S(═O)2Rb group, in which Rb is as defined infra, with the provisos that when Rb is —NRd1Rd2:
• Rd1 and Rd2 are not both H,
• when Rd1 is H, then Rd2 is not C1-C6-alkyl,
• Rd1 and Rd2 are not both C1-C6-alkyl,
• or
• a —C(═O)Rb group, in which Rb is as defined infra;
• or
• b) an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, said aryl, heteroaryl, cycloalkyl or heterocycloalkyl group being substituted with one or more —(CH2)oR14 groups, in each occurrence of said —(CH2)oR14 group:
• o is an integer of 1 or 2;
• and
• R14 is as defined infra;
• or
• c) a C2-C10-alkenyl or C5-C10-cycloalkenyl group, said C2-C10-alkenyl or C5-C10-cycloalkenyl group being optionally substituted with one or more —(CH2)oR14 groups, in which o and R14 are as defined infra;
• R7 and R8 are independently a hydrogen atom, a —N(R12)(R13), —OH, —C1-C6-alkoxy, —C1-C6-alkyl, —CF3, —O—(CH2)n—(CH(OR11))—(CH2)m—R9, —O—(CH2)n-cycloalkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, in which aryl, heteroaryl, cycloalkyl, or heterocycloalkyl are, independently of each other, optionally substituted with one or more halogen atoms, C1-C6-alkyl or C1-C6-alkoxy groups;
• R9 and R10 are independently —OH, —C1-C6-alkoxy, halogen, heteroaryl, —NRd1Rd2 or —N(R12)(R13);
• R11, R12 and R13:
• are independently a hydrogen atom, a C1-C6-alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, in which C1-C6-alkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl are, independently of each other, optionally substituted with one or more —(CH2)oR14 groups,
• or
• R12 and R13, together with the N atom to which they are bound, form a 5-, 6-, or 7-membered heterocyclic ring which optionally comprises one or more additional heteroatoms, which optionally comprises one or more —C(═O)— or —S(═O)2 groups, and which is optionally substituted with one or more —(CH2)oR14 groups;
• R15 is, in each occurrence, independently, a halogen atom, a C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxyalkyl, cycloalkyl, heterocycloalkyl, —ORc, —NRd1Rd2, —CN, —NHS(═O)2H, —NRaS(═O)2Rb, —S(═O)2Rb or —C(═O)Rb group;
• R15 is, in each occurrence, independently, a hydrogen atom or a C1-C6-alkyl group, in which at least one R15 groups is C1-C6-alkyl;
• n is, in each occurrence, independently, an integer of 0, 1, 2, 3, or 4;
• m is, in each occurrence, independently, an integer of 0, 1, or 2;
• and
• o is, in each occurrence, independently, an integer of 0, 1, or 2;
• Ra is, in each occurrence, independently, a hydrogen atom or a C1-C6-alkyl group;
• Rb is, in each occurrence, independently, an —OH, —ORC, —SRc, —NRd1Rd2, a C1-C6-alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, in which C1-C6-alkyl, heteroaryl, cycloalkyl and heterocycloalkyl are, independently of each other, optionally substituted one or more times with a halogen atom, an —OH, C1-C6-alkyl or C1-C6-alkoxy group;
• Rc is, in each occurrence, independently, a hydrogen atom, a —C(═O)Re, —S(═O)2Re, C1-C6-alkyl, C1-C6-haloalkyl cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, in which C1-C6-alkyl, C1-C6-haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, are, independently of each other, optionally substituted one or more times with a halogen atom, an —OH, aryl, —ORf, —NRd1Rd2, or —OP(═O)(ORf)2 group;
• Rd1, Rd2, Rd1, Rd2:
• are, in each occurrence, independently of each other, a hydrogen atom, a C1-C6-alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C(═O)Re, —S(═O)2Re, or —C(═O)NRg1Rd2 group, in which C1-C6-alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl are, independently of each other, optionally substituted one or more times, the same way or differently, with a halogen atom, a C1-C6-alkyl, an —OH or aryl, —NRg1Rg2, —ORf, —C(═O)Re, —S(═O)2Re, or —OP(═O)(ORf)2 group;
• or
• Rd1 and Rd2, together with the nitrogen atom to which they are bound, form a 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycloalkyl ring, which is optionally substituted one or more times, the same way or differently, with a halogen atom, a C1-C6-alkyl, —NRg1Rg2, —ORf, —C(═O)Re, —S(═O)2Re, or —OP(═O)(ORf)2 group;
• and the carbon backbone of which is optionally interrupted one or more times, in the same way or differently, with NH, NRd3, O, or S, and is optionally interrupted one or more times, in the same way or differently, with a —C(═O)—, —S(═O)—, and/or —S(═O)2-group, and optionally contains one or more double bonds;
• Rd3 is a hydrogen atom, a C1-C6-alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, in which C1-C6-alkyl or cycloalkyl are, independently of each other, optionally substituted one or more times with a halogen atom, an —OH, C1-C6-alkyl, cycloalkyl, C1-C6-haloalkyl or C1-C6-alkoxy group;
• Re is an —NRg1Rg25 C1-C6-alkyl, cycloalkyl, C1-C6-alkoxy, aryl or heteroaryl group;
• Rf is a hydrogen atom, a —C(═O)Re, C1-C6-alkyl, C1-C6-haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, in which C1-C6-alkyl, C1-C6-haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl are, independently of each other, optionally substituted one or more times with a halogen atom, an —OH, C1-C6-alkoxy, aryl, or —NRg1Rg2 group;
• Rg1, Rg2 are, independently of each other, a hydrogen atom, a C1-C6-alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group;
• or
• Rg1 and Rg2 together with the nitrogen atom to which they are bound, form a 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered heterocycloalkyl ring, which is optionally substituted one or more times, in the same way or differently, with a halogen atom, an —OH, C1-C6-alkyl, C1-C6-alkoxy group;
• and the carbon backbone of which is optionally interrupted one or more times, in the same way or differently, with NH, NRa, O, S, and is optionally interrupted one or more times, in the same way or differently, with a —C(═O)—, —S(═O)—, and/or —S(═O)2— group, and optionally contains one or more double bonds;
• with the proviso that:
• X—R6 is not (O or NH)—(CH2)r—Rr,
• where Rr is NRs1Rs2 in which
• r=1-4, and
• Rs1, Rs2=independently hydrogen, C1-C8 alkyl, or taken together with the nitrogen to which they are attached, form a 3-10 member cyclic ring optionally containing one oxygen atom or one sulfur atom or one NH or N—C1-C8 alkyl group;
• or a tautomer, stereoisomer, physiologically acceptable salt, hydrate, solvate, metabolite, or prodrug thereof.