Arildihidroisoquinolinas replaced with Aminoalcohol, Process for their Preparation and their use as medicines

摘要

Item 1: a formula compound (1)en la que los significados son D N C (R1)R1, R1',R1 ".R1 "is independent of H, F, CI, Br, I, oh, CF3, NO2, CN, ocf3, o-hc-6, o-alcoxi C1-4, C1-4, s-c1-6, C1-6, C1-6, acquilo C1-6, alquenilo c2-6, C3-8, o-cyclo-c3-8, acquin-6, leno-c0-arilo, s-r3 (R3),So2ch3, COOH, COO asphalt C1-6, con (R5) (R6),N (R7) CO (R8)N (R9) SO2 (R10)CO (R11) o (C (R12) (R13)) x- O (R14)R3, R4, R5, R6, R7, R9 independently of each other H or C1-8 alkyl; or R3 and R4, R5 and R6 form independently of each other optionally together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N 1-6 alkyl, oxygen and sulfur; R8, R10, R11 independently of each other H or C1-8 alkyl, or aryl; R12, R13 independently of each other H or C1-8 alkyl; R14 H, C1-6 alkyl or aryl; x 0, 1, 2, 3, 4, 5 or 6; R2 H, F, CI, Br, I, OH, CF3, NO2, CN, OCF3, O-C1-6 alkyl, O-C1-4 alkoxy C1-4 alkyl, S-C1-6 alkyl, C1-6 alkyl, C2-6 alkenyl, C3-8 cycloalkyl,O-cycloquino C3-8, cycloquinoo C3-8, tar c2-6, c0-8-arilo, o-coquileno c0-8-arilo, s-arilo, n (R15) (R16),So2-ch3, COOH, COO asphalt C1-6, con (R17) (R18),N (R19) CO (R20)N (R21) SO2 (R22)CO (R23) o (C (R24) (R25)) x -O (R26)R15, R16, R17, R18, R19, R21 independently of each other H or C1-8 alkyl; or R15 and R16, R17 and R18 independently form each other and optionally together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the group of NH, N 1-6 alkyl, oxygen and sulfur; R20, R22, R23 independently of each other H, C1-3 alkyl or aryl; R24, R25 independently of each other H or C1-8 alkyl; R26 H, C1-6 alkyl or aryl; preferably H or C1-6 alkyl; x '0, 1, 2, 3, 4, 5 or 6; Y C (R27) (R27 ') C (R28) (R28') or C (R29) C (R29 ');R27, R27 ',R28, R28 ',R29, R29 ` independent of H or c1-8; x s, O, C (R30) = C (R30 ';6, or c3-8-8-8-8-8-8-8-8, or c8-8-8-8 n (R15) (R16),So2-ch3, COOH, COO asphalt C1-6, con (R17) (R18),N (R19) CO (R20)N (R21) SO2 (R22)CO (R23) o (C (R24) (R25)) x -O (R26)A liaison or canning consisting of 1 to 8 members selected from the group consisting of O, s, SO2, n (R31);CO C (R32) (R33)C (R34) 3DC (R34)cyclopropylene and CsC resulting in a chemically reasonable radical; R31, R34, R34 'independently of each other H or C1-8 alkyl; R32, R33 independently of each other H, C1-8 alkyl, OH or O-C1-6 alkyl; B H, N (R35) (R36),1. Hydroxy-c1-4 tar, c1-8 tar, Alcoy c1-4-c1-4-tar, C1-4 alquenilo C2-8, c12-8 tar, a monkey ring,Double...tri- o espiroc clico de 3 a 10 miembros que puede comprender de 0 a 4 hetero tomos seleccionados entre el grupo de oxigeno nitrogeno y azufre donde el sistema de anillos puede estar adicionalmente sustituido con uno oms de los siguientes sustituyentes F CI Br CF3 NO2 CN CON (R38) (R39)hidroxi COO (R40)N (R41) COalquilo C1-6 N (R42) (R43)SO2CH3, SCF3 or S-C1-6 alkyl; R35, R36, R37, R38, R39, R40, R41, R42, R43 independently of each other H or C1-8 alkyl; or R38 and R39, R42 and R43 form independently of each other optionally together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N 1-6 alkyl, oxygen and sulfur; L a bond or C1-3 alkylene; Q N (R53 ') (R54'),Saturated or partially unsaturated ring structure, monkeybi- or spirocyclic, which has a nitrogen atom and 0-3 additional heteroatoms selected from the group of N, O and S, where the rings of the structure can be spiro-bonded, condensed or bonded, and where the ring system it may be substituted with one or more of the following substituents: F, OH, CF3, CN, OCF3, oxo, O-C1-8 alkyl, C1-4 alkoxy-C1-4 alkyl, C1-6 alkyl, C2-6 alkenyl , C2-6 alkynyl, CO (R44),(C (R45) (R46)) o-R47 and CO (C (R45) (R46)) p-R48; R44 H, C1-8 alkyl; R45, R46 independently of each other H, C1-8 alkyl, OH, C3-8 cycloalkyl or C1-4 alkoxy-C1-4 alkyl; or, p independently from each other 0, 1, 2, 3, 4, 5 or 6; R47, R48 independently of each other OH, F, O-C1-8 alkyl, CON (R49) (R50),N (R51) CO (R52)N (R53) (R54)CO2 (R55)So2me, CN, a 3-10 ring system consisting of 0 to 3 heteroatoms selected from group n or group s, can be replaced by one or more of the following alternatives: F, CI, Br, CF3, c1-8 tar, c1-8 tar, alcoxi c1-4-c1-4 tar, CO (R56),oxo and OH; R49, R50, R51, R52, R55, R56 independently of each other H or C1-8 alkyl; or R49 and R50 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group, N-C1-6 alkyl , oxygen and sulfur; R53, R54, R53 ',R54'independent between Si h, c1-8 tar, Alcoy c1-4-c1-4-tar, alquenilo C3-8, aquinio C3-8, CO (R57),(C (r58) (R59)) q-r60, CO (C61) (R62)), r-r63 or co - (CH2) or '- o' - or - pitch C1-6; or R53 and R54 or R53 'and R54 "form a single ring together with nitroglycerin.Bi-O helical atom, consisting of 4 to 10 members, includes 0 to 3 additional heteroatoms selected from group n, group O and group s in addition to nitration atom, and can be supplemented by one or more of the following substitutes: F, Cl, Br, CF3, o-tar c1-8, C1-6 tar, CO (R64),Oxy, oh, alcoxi c1-4-c1-4-tar, c1-4-alkyl, with (R65) (R66),N (R67) CO (R68)N (R69) (R70)CO2 (R71) and SO2-C1-6 alkyl; or '0, 1, 2, 3, 4, 5 or 6; R58, R59 independently of each other H, C1-6 alkyl or OH; R57, R61, R62, R64, R65, R66, R67, R68, R69, R70, R71 independently of each other H or C1-6 alkyl; R69 and R70 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group, N-C1-6 alkyl, oxygen and sulfur; q, r independently from each other 0, 1, 2, 3, 4, 5 or 6; R60, R63 independently of each other OH, F, O-C1-6 alkyl, CN, COO (R78),N (R74) COalquilo C1-6 N (R76) (R77)And (R72) (R73),So2-c1-6, a monkey ringbi- o espiroc clico de 3-12 miembros que puede comprender uno oms hetero tomos del grupo de NO y S y el anillo de 3-12 miembros puede comprender sustituyentes adicionales tales como F CI Br OH CF3 NO2 CN OCF3 oxo O-alquilo C1 COO (R78)SO2-C1-6 alkyl and COOH; R72, R73, R74, R76, R77, R78 independently of each other H or C1-8 alkyl; or R72 and R73, R76 and R77 form independently of each other optionally together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-C1-6 alkyl, oxygen and sulfur; and pharmaceutically acceptable salts thereof; where in case L is C1-3 alkylene, B is not an aromatic radical, nor a cycloalkyl radical, nor a 2-alken-1-yl radical nor a 2-cycloalken-1-yl radical, and C ( R34 ') C (R34') for group A.