Non-steroidal compounds useful as moderators of the activity of the glucocorticoid receptor AP-1 and / or NF-kappa b and their use

摘要

A compound with the structure of the formula (Ia) or (Ib): ** Formula ** or enantiomers, diastereomers, or pharmaceutically acceptable salts thereof, wherein: R1 is hydrogen, C1-3 alkyl, C2-3 alkenyl , C2-3 alkynyl, cyclopropyl, halogen, -CH2F, CHF2, -CF3, -CN, C1-3 alkoxy, -NRdRc, -C (O) ORd or -C (O) NRdRc; R2 is hydrogen or C1-3 alkyl; R3 is hydrogen, OH, F, Cl or C1-3 alkyl; R4 is i) hydrogen, ii) C1-3 alkyl optionally substituted with OH, F or phenyl, iii) C2-4 alkenyl or C2-4 alkynyl, iv) aryl or aryl substituted with one or more of halogen, C1-3 alkyl , methoxy and / or -CN, v) -CRaRbRc, -C (O) Rc, - (CH2) pC (O) NHRc, - (CH2) pNHRc, - (CH2) pNHC (O) ORc or - (CH2) pNHC (O) NHRc, in which p is zero, 1, 2 or 3, or vi) -CRaRbRc in which Rb and Rc together with the carbon atom to which they are attached form a heterocycle of 1 or 2 rings with at least one heteroatom chosen from N, O, and S; or R3 and R4 together with the carbon atom to which they are attached, form a saturated heterocyclic ring of 5 to 7 members with between 1 and 2 heteroatoms independently selected from between N, O and S; each R5 is independently C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, F, Cl, -CN, C1-3 alkoxy and / or -OCF3; R6 is hydrogen, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C2-4 alkenyl, C2-4 alkynyl, F, Cl, -CN, C1-3u alkoxy -OCF3; R7 is aryl or heterocycle optionally substituted with one or more of C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, CNy / or halogen; Ra is hydrogen, C1-3 alkyl or C1-3 alkyl substituted with OH or F; Rb is hydrogen, OH, C1-3 alkyl, C1-3 alkoxy or C1-3 alkyl substituted with OH or F; Rc is: i) C1-5 alkyl optionally substituted with OH, aryl or haloaryl, ii) C1-3 haloalkyl, C3-6 cycloalkyl or C2-4 alkenyl, iii) C2-4 alkynyl optionally substituted with aryl, iv) aryl optionally substituted with one or more of halogen, methoxy, -S (O) (C1-3 alkyl), -S (O) 2 (C1-3 alkyl), - CN, C1-3 alkyl, C1-3 hydroxyalkyl, C1 haloalkyl -3, saturated heterocycle and / or -S- (C1-3 alkyl), ov) aryl or heteroaryl of 1 or 2 rings optionally substituted with one or more of C1-4 alkyl, halogen, -C (O) OH, - C (O) O (C1-3 alkyl), -C (O) NH (C1-3 alkyl), or -C (O) N (C1-3 alkyl) 2;