Aryl carbonyl derivatives as therapeutic agents

A compound of formula (Ib)

• wherein
• R24 is selected from the group consisting of hydrogen, halogen, —C(O)OR2, —CN, —CF3, —OCF3, —NO2, —OR2, —NR2R3, C1-6-alkyl-Z-, cycloalkyl-Z-, heterocyclyl-Z-, aryl-Z-, or heteroaryl-Z-, N(R4R5)—C1-6-alkylene-Z-, R6—W1-Z-, R6—W1—N(R4)-Z-, R6—N(R4)-Z, and R6—W1—C1-6-alkylene-Z-;
• R2 and R3 independently of each other are selected from the group consisting of hydrogen, C1-6-alkyl, aryl-C1-6-alkylene-, heteroaryl-C1-6-alkylene-, C1-6-alkyl-arylene-, C1-6-alkyl-heteroarylene-, heteroaryl, or aryl;
• Z is a direct bond, —O—, —NH—, —NHCH2—, —S—, —SO2—, —C(O)NH—, —NHC(O)—, —N(H)CON(H)—, —N(CH3)CONH—, —N(H)SO2—, —SO2N(H)—, —C(O)—O—, —N(H)SO2N(H)—, or —O—C(O)—;
• R4, R5, and R6 independently of each other are selected from the group consisting of hydrogen, aryl, C1-6-alkyl, heteroaryl-C1-6-alkylene-, and aryl-C1-6-alkylene-;
• W1 is a direct bond, —O—, —C(O)—, —NH—, —S—, —SO2—, —C(O)NH—, —NHC(O)—, —N(H)CON(H)—, —N(H)SO2—, —SO2N(H)—, —C(O)—O—, —N(H)SO2N(H)—, or —O—C(O)—;
• L1 is -D-alkylene-E-, —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —N(R11)—, or —C(═N—OR12);
• D is a direct bond or —O— and E is a direct bond or —O—;
• R11 is hydrogen or C1-6-alkyl;
• R12 is hydrogen or C1-6-alkyl;
• G1 is C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-10-cycloalkyl or C3-10-heterocyclyl, optionally substituted with one or more substituents selected from the group consisting of —CN, —CF3, —OCF3, —OR18, —NR18R19, C3-10-cycloalkyl and C1-6-alkyl;
• R18 and R19, independently of each other, are hydrogen or C1-6-alkyl;
• L2 is a direct bond, —N—(R20)—, -alkylene-N(R20)—, -alkenylene-N(R20)—, or -alkynylene-N(R20)—;
• R20 is hydrogen;
• L3 is —C(O)—, —C(O)—C(O)— or —C(O)CH2C(O)—;
• R1 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of R33, R34, and R35;
• R33, R34, and R35 independently of each other are selected from the group consisting of —CHF2, —CF3, —OCF3, —OCHF2, —OCH2CF3, —OCF2CHF2, —S(O)2CF3, —SCF3, —OR52, —NR52R53, —SR52, —NR52S(O)2R53, —S(O)2NR52R53, —S(O)NR52R53, —S(O)R52, —S(O)2R52, —C(O)NR52R53, —OC(O)NR52R53, —NR52C(O)R53, —CH2C(O)NR52R53, —OCH2C(O)NR52R53, —CH2OR52, —CH2NR52R53, —OC(O)R52, —C(O)R52 and —C(O)OR52;
• R52 and R53 independently of each other are selected from the group consisting of hydrogen, C1-6-alkyl, aryl-C1-6-alkylene, heteroaryl-C1-6-alkylene, heteroaryl, and aryl;
• and
• R52 and R53, when attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, may form a 3— to 8—membered heterocyclic ring optionally containing one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and optionally containing one or two double bonds;
• R43 is selected from the group consisting of
• —SR54, —S(O)2R54, halogen, —C1-6-alkylene-C(O)OR54, —C(O)OR54,
• heterocyclyl and heterocyclyl-C1-6-alkylene-, of which the heterocyclyl moieties may be optionally substituted with one or more substituents independently selected from R70;
• and
• heteroaryl or heteroaryl-C1-6-alkylene-, of which the heteroaryl moieties optionally may be substituted with one or more substituents selected from the group consisting of halogen, —C(O)OR54, —CN, —CF3, —OCF3, —NO2, —OR54, —NR54R55 and C1-6-alkyl;
• R70 is ═O, —C(O)CH3, —S(O)2CH3, —CF3, —C(O)O—R75, —(CH2)1-3C(O)O—R75 or C1-6-alkyl;
• R54 and R55 independently of each other are hydrogen, C1-6-alkyl, aryl-C1-6-alkylene-, heteroaryl-C1-6-alkylene, heterocyclyl, heterocyclyl-C1-6-alkylene, heteroaryl, or aryl, each of which is optionally substituted with one or more substituents independently selected from R71;
• or
• R54 and R55 independently of each other are hydrogen or —(CHAR72)u—(CHAR73)v—W6, wherein
• u is 0, 1 or 2;
• v is 0, 1 or 2;
• R72 and R73 independently of each other are hydrogen, C1-6-alkyl, C1-6-alkyl-arylene- aryl, hydroxy, hydroxyalkyl, —C(O)O—R75, amino, or aminoalkyl;
• W6 is hydrogen, —O—R75, —C(O)O—R75, —C(O)—R75, —CONR75R76, —NR75R76, —NHCH2C(O)R75, —NHC(O)R75, —NHC(O)OR75, —S(O)2R75, —NHS(O)2R75, alkylamino, or dialkylamino, or
• W6 is a five or six membered ring wherein at least one ring atom is nitrogen and the remaining ring atoms are either carbon or oxygen or optionally substituted with C1-6-alkyl, —C(O)O—R75, —(CH2)1-3C(O)O—R75, ═O;
• or
• W6 is phathalimido or heterocyclyl, or
• R54 and R55, when attached to the same nitrogen atom, together with the nitrogen atom to which they are attached, may form a 3 to 8 membered hecerocyclic ring optionally containing one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and optionally containing one or two double bonds, and optionally substituted with one or more C1-6-alkyl groups;
• R71 is ═O, C1-6-alkyl, cycloalkyl, —C(O)O—R75, —(CH2)1-3C(O)O—R75, —(CH2)1-3NR75R76, —OH or amino;
• R75 and R76 independently of each other is hydrogen, halogen, —OH, —CF3, or C1-6-alkyl optionally substituted with —NH2;
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof.