| abstract |
It refers to new compounds that are selective antagonists of the glucocorticoid receptor of the liver, to methods for the preparation of said compounds, and to methods for using said compounds in the treatment and regulation of metabolism, especially in the reduction of levels. of blood glucose. The compounds mentioned are compounds according to formula (1): R1 is selected from COOH, C (O) NHOH, C (O) COOH, SO3H, P (O) (OH) (OR8); P (O) (OH) [N (R9) (R10)] and heteroaryl, where any heteroaryl residue can be optionally substituted in one or more positions independently of each other by a group selected from C1-6 alkyl , perfluoro C1-6 alkyl, halogen, cyano, nitro, R8O, R8S, R8S (O), R8S (O) 2, and (R9) (R10) N; R2 and R3 are independently selected from each other of hydrogen, halogen, and C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkyl halo, perfluoro C1-6 alkyl, C1-6 alkyloxy halo , perfluoro C1-6 alkyloxy, and C1-6 alkylthio halo, with the proviso that one of R2 or R3 is not hydrogen; R4, R5, R6 and R7 are independently selected from the others of (i) C1-12 alkyl and perfluoro C1-6 alkyl, where any residue can be optionally substituted in one or more positions independent of each other by a group selected from A; (ii) C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein any residue can be optionally substituted in one or more positions independently of one another by a group selected from B; R4 and R5 are independently selected from (iii) C3-8 heterocycloalkyl, optionally substituted by a group selected from B; (iv) aryl and heteroaryl, where any residue can be optionally substituted in one or more positions independently of one another by a group selected from C; R4 is optionally selected from halogen, R8O, R8S, R8S (O), R8S (O) 2, and (R9) (R10) N, R8C (Z) N (R11), (R9) (R10) NC ( Z) N (R11), R8S (O) 2N (R11), and (R9) (R10) NS (O) 2N (R11); R6 and R7 are optionally and independently selected from hydrogen, halogen, R8O, R8S, R8S (O), R8S (O) 2, and (R9) (R10) N, R8C (Z) O , R8OC (Z) O, R8C (Z) N (R11), R8OC (Z) N (R11), R8S (O) No, (R9) (R10) NC (Z) O, (R9) (R10) NS (O) 2O, R8S (O) 2N (R11), (R9) (R10) NS (O) 2; and (R9) (R10) NS (O) 2N (R11), with the proviso that R8 is not hydrogen in R8OC (Z) O, R8S (O) nO, and R8S (O) 2N (R11), and that only one of R6 and R7 is hydrogen, and that if R6 is HO, R7 is hydrogen, and if R7 is OH, R6 is hydrogen, R8, R9, R10 and R11 are independently selected from each other, from (v ) hydrogen; (vi) C1-12 alkyl, perfluoro C1-6 alkyl, where any of its residues can be optionally substituted in one or more positions independently of each other, by a group selected from A; (vii) C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, where any residue can be optionally substituted in one or more positions independently of one another by a group selected from B; (viii) aryl and heteroaryl, where any residue can be optionally substituted in one or more positions independently of one another by a group selected from C; or where any pair of R8, R9, R10 and R11 together with the atom or atoms to which they are attached form a ring that has 3 to 7 elements, and where the ring optionally contains C1-3 heteroatoms or 1 to 3 double joints, and which, optionally, is replaced by a group selected from B; A is selected from halogen, perfluoro C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, C3-8 heterocycloalkyl, heteroaryl, cyano, nitro, azido, Z, R8O, R8C (Z) , R8C (Z) O, R8OC (Z), R8S, R8S (O), R8S (O) 2, R8S (O) 2O, R8OS (O) 2, (R9) (R10) N, (R9) (R10 ) NC (Z), (R9) (R10) NC (Z) O, R8C (Z) N (R11), R8OC (Z) N (R11), (R9) (R10) NC (Z) N (R11) , (R9) (R10) NS (O) 2, R8S (O) 2N (R11), (R9) (R10) NS (O) 2N (R11), and R8SC (Z) N (R11), where any residue of perfluoro C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 heterocycloalkyl optionally is substituted in one or more positions independently of one another by a group selected from B, and in addition wherein any aryl or heteroaryl residue is optionally substituted in one or more positions independently of one another by a group selected from C; B is defined as A or a C1-6 alkyl optionally substituted in one or more positions independently of one another by a group selected from D, with the proviso that if B is directly attached to a double bond or a triple bond, or to a carbon directly attached to a heteroatom, B is not HO, HS, R9HN, (R9) (R10) NC (Z) NH, (R9) (R10) NS (O) 2NH, or R8S ( O) 2NH, and with the additional condition that if B is directly attached to a double union or triple union, B is not Z, C is defined as A, or a C1-6 alkyl group optionally substituted in one or more positions independently of each other by a selected group of D, with the proviso that C is not Z; D is selected from halogen, cyano, nitro, azido, Z, R8O, R8C (Z), R8C (Z) O, R8OC (Z), R8S, R8S (O), R8S (O) 2, R8S (O) 2O , R8OS (O) 2, (R9) (R10) N, (R9) (R10) NC (Z), (R9) (R10) NC (Z) N (R11), (R9) (R10) NS (O ) 2, R8S (O) 2N (R11), (R9) (R10) NS (O) 2N (R11); and is selected from hydrogen, halogen, hydroxy, C1-6 alkoxy, halo C1-6 alkoxy, perfluoro C1-6 alkoxy, C1-6 acyloxy, C1-6 alkylthio, C1-6 alkylthio halo, C1-6 alkylthio perfluoro, alkylsulfonyloxy C1-6, azido and (R9) (R10) N; Z is a substituent connected to a double bond, and is selected from O =, S =, R8N =, (R9) (R10) NN =, R8ON =, (R9) (R10) NS (O) 2N =, NCN = , O2NCH = y (R9) (R10) C =; n is 0, 1, 2 or 3 or its stereoisomeric salts or prodrugs acceptable for pharmaceutical use. |