Organic compounds

摘要

3-(4-(Cyclic amido or ureido)-piperidino)-benzamide (or mono-, di- or or triaza analog) derivatives (I) are new. Piperidine derivatives of formula (I) and their tautomers, diastereomers, enantiomers, hydrates, mixtures, salts and hydrated salts are new. R 1>cyclic amide or urea residue of formula (II); G-L : N, N-C(R 51>) 2, C=N, C(R 51>), C(R 51>)-C(R 51>) 2, C(R 51>)-C(R 51>) 2-C(R 51>) 2, C=C(R 51>)-C(R 51>) 2, C(R 51>)-C(R 51>)=C(R 51>), C(R 51>)-C(R 51>) 2-N(R 52>), C=C(R 51>)-N(R 52>), C(R 51>)-C(R 51>)=N, C(R 51>)-N(R 52>)-C(R 51>) 2, C(R 51>)-N=C(R 51>), C(R 51>)-N(R 52>)-N(R 52>), C=N-N(R 52>), N-C(R 51>) 2-C(R 51>) 2, N-C(R 51>)=C(R 51>), N-C(R 51>) 2-N(R 52>), N-C(R 51>)=N, N-N(R 52>)-C(R 51>) 2or N-N=C(R 51>); Q-T : C(R 6>) 2-C(R 6>) 2, C(R 6>)=C(R 6>), N=C(R 6>), C(R 6>) 2-CO, COC(R 6>) 2, C(R 6>) 2-S(O) mor C(R 6>) 2-N(R 6>) (where all C(R 6>) 2moieties are optionally replaced by a ring; and adjacent R 6>groups optionally together form a ring); R 2>H, F, CN, COOR 21>or A'; R 21>H or alkyl; A' : 1-3C alkyl (optionally substituted (os) by one or more F); ; R 3>H; or alkyl, cycloalkyl, 5-7C cycloalkenyl, aryl, heterocyclyl, aryl- or heteroaryl-fused 5-7C cycloalkyl or heteroaryl (all os); R 4>as for R 3>; or NR 3>R 4>os 5-7 membered saturated heterocycle (optionally fused with os 5-7 membered cycloalkyl or heterocyclyl); (b) os 5-7 membered monounsaturated heterocycle, fused with os phenyl or 5-6 membered heteroaryl; or (c) os heteroaryl; R 51>H, alkyl, CN, OH, OA'or A'''; A''' : 1-3C mono- or polyfluoroalkyl; R 52>H or alkyl; R 6>H, alkyl, alkenyl, alkynyl or cycloalkyl; or aryl, heteroaryl or heterocyclyl (all os); U 1N, N(O) or C-R 10>; V 1N, N(O) or C-R 11>; X : N, N(O) or C-R 12>; Y 1N or C-R 13>, provided that not more than 3 of U 1, V 1, X and Y 1are N; R 10>H, halo, CN, A, CF 3, alkynyl or -alkynyl-OH; A : 1-3C alkyl; R 11>H, Cl, A, NR 111>R 112>or OA; R 111>H or alkyl; R 112>H or SO 2A; R 12>H, halo, CN, A, CF 3or alkynyl; R 13>H, halo or A; unless specified otherwise alkyl moieties have 1-6C, alkenyl or alkynyl moieties 2-6C, cycloalkyl moieties 3-6C and cycloalkenyl moieties 5-6C. [Image] ACTIVITY : Analgesic; Antimigraine; Antidiabetic; Cardiant; Antidiarrheic; Dermatological; Vulnerary; Antipruritic; Antiinflammatory; Osteopathic; Antirheumatic; Antiallergic; Antiasthmatic; Antibacterial; Vasotropic; Immunosuppressive; Anti-HIV; Gynecological. MECHANISM OF ACTION : Calcitonin gene-related peptide (CGRP) antagonist. 1-(1-(6-(5-Fluoro-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-pyrimidin-4-yl)-piperidin-4-yl)-1,3-dihydroimidazo-(4,5-b)-pyridin-2-one (Ia) had K ivalue of 2 nM in a CGRP antiagonist assay in vitro.