Substituted benzene compounds as modulators of the glucocorticoid receptor

A compound of the general formula I,

• wherein
• A is C—R1b;
• one of R1c or R1d is —X—R6, wherein
• X is selected from the group consisting of a bond, —CH2—CH2—, —CH═CH—, —O—, —O—CH2—, —CH2—O—, —O—CH2—CH2—O—, —C(═O)—, —S(═O)2—O—, —C(═O)—NR7—, —NR7—C(═O)—, —S(═O)2—NR7—, —NR7—S(═O)2— and —NR8—, wherein
• R7 is hydrogen or C1-7-alkyl, and
• R8 is selected from the group consisting of hydrogen, C1-7-alkyl and pyridyl, said pyridyl ring being substituted by carboxyl;
• R6 is selected from the group consisting of
• phenyl, said phenyl being substituted by a substituent selected from the group consisting of carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxy, C1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxy and C3-7-cycloalkyl substituted by carboxyl or C1-7-alkoxycarbonyl, and, in addition, optionally substituted by one or two substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy, cyano, C1-7-alkylsulfonyl, C1-7-alkoxy and halogen-C1-7-alkoxy,
• phenyl-C1-7-alkyl, wherein the phenyl is substituted by a substituent selected from the group consisting of carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxy, C1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl and C1-7-alkoxycarbonyl-C1-7-alkoxy and, in addition, optionally substituted by one or two substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy, cyano, C1-7-alkylsulfonyl, C1-7-alkoxy and halogen-C1-7-alkoxy,
• heteroaryl, said heteroaryl being substituted by a substituent selected from the group consisting of carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxy, C1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl and C1-7-alkoxycarbonyl-C1-7-alkoxy and, in addition, optionally substituted by one or two substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy, cyano, C1-7-alkylsulfonyl, C1-7-alkoxy and halogen-C1-7-alkoxy,
• heterocyclyl, said heterocyclyl being substituted by a substituent selected from the group consisting of carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxy, C1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkyl and C1-7-alkoxycarbonyl-C1-7-alkoxy
• R1a, R1b, R1e, and the other one of R1c or R1d are each independently selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxy, halogen-C1-7-alkyl-sulfonyloxy, hydroxy, hydroxy-C1-7-alkyl, C1-7-alkoxy, C1-7-alkoxy-C1-7-alkoxy, hydroxy-C1-7-alkoxy, amino-C1-7-alkoxy, cyano, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxy, C1-7-alkoxycarbonyl, C1-7-alkoxycarbonyl-C1-7-alkoxy, C1-7-alkoxycarbonylamino-C1-7-alkoxy, C1-7-alkylcarbonyloxy-C1-7-alkoxy, aminocarbonyl-C1-7-alkoxy, di-C1-7-alkylamino, di-C2-7-alkenylamino and C1-7-alkylsulfonylamino;
• R2 is selected from the group consisting of C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, carboxyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkyl, triazolyl-C1-7-alkyl and phenyl, said phenyl being unsubstituted or substituted by one, two or three halogen groups;
• R3 is hydrogen or C1-7-alkyl;or R2 and R3 together with the carbon atom they are attached to form a C3-C5-cycloalkyl ring;
• R4 is a heteroaryl ring selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 2-oxo-1,2-dihydropyridinyl, quinolinyl, isoquinolinyl, cinnolinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, thienyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, quinoxalinyl, benzothiazolyl, benzotriazolyl, indolyl, and indazolyl, said heteroaryl ring being unsubstituted or substituted by one, two or three substituents selected from the group consisting of
• halogen, halogen-C1-7-alkyl, cyano, C1-7-alkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxy, C1-7-alkoxy-C1-7-alkoxy, cyano-C1-7-alkoxy, hydroxy-C1-7-alkoxy, halogen-C1-7-alkoxy, carboxyl, carboxyl-C1-7-alkyl, carboxyl-C1-7-alkoxy, C1-7-alkoxycarbonyl,
• C1-7-alkoxycarbonyl-C1-7-alkyl, C1-7-alkoxycarbonyl-C1-7-alkoxy,
• R9R10N-carbonyl-C1-7alkoxy, wherein R9 and R10 are independently selected from hydrogen or C1-7-alkyl or R9 and R10 together with the nitrogen atom they are attached to form a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, morpholine and thiomorpholine,
• phenyl, said phenyl being unsubstituted or substituted by one, two or three substituents selected from the group consisting of halogen, halogen-C1-7-alkyl, C1-7-alkyl, hydroxy, cyano, carboxyl, C1-7-alkoxycarbonyl and C1-7-alkoxy;
• pyridyl,
• heterocyclyl selected from the group consisting of pyrrolidine and piperidine, said heterocyclyl ring being unsubstituted or substituted by carboxyl or C1-7-alkoxy-carbonyl,
• phenyl-C1-7-alkyl,
• phenyloxy and
• phenyl-C1-7-alkoxy;
• and
• R5 is hydrogen or methyl;
• or a pharmaceutically acceptable salt thereof.