Patent EP-2426106-A1 (EP)
Inventor: SCHIEMANN KAI
IPC: A61K31/4184
Filed: 2008-09-19
Abstract: Substituted piperidine- and piperazine compounds (I), and their tautomers, salts or stereoisomers, including their mixtures in all ratios, are new. Substituted piperidine- and piperazine compounds of formula (I), and their tautomers, salts or stereoisomers, including their mixtures in all ratios, are new. R 1> : binuclear unsaturated or aromatic heterocycle with 1-4 N-, O- and/or S atoms (unsubstituted or 1-3 times substituted by A, hal, NR 2, (CR 2) nCN, OR 5>and/or =O); D 1> : C or S; G : N or C; either R 2> : absent (when G is N) or H or Ar 2>(when G is C); or CR 2>+R 2>, (E-W 1>)R 2>+R 2> : spirocyclic ring of 3H-isobenzofuran-1-one-3,3-diyl, chroman-3-one-2,2-diyl, substituted oxazolidin-2-one moiety of formula (a) or imidazolidine-2,4-dione-5,5-diyl; Q : optionally branched 1-4C alkylene, where 1-5 H atoms are substituted by A, (CR 2) n[X(CR 2) n] p-Y 1>, F and/or Cl; R 3> : H, A, Ar 1>, OR, SR, NR 2, hal, NO 2, CN or (CR 2) n[X(CR 2) n] p-Y 1>; X : O, NR or CR 2; Y 1> : OR or NR 2; R 5> : H or optionally branched 1-6C alkyl, where 1-7 H atoms are substituted by F and/or Cl; E : COO(CR 2) n, COO(CRR 4>), CO(CR 2) mO, CONH(CR 2) n, C(=S)NH(CR 2) n, S(O) qNH(CR 2) n, S(O) q(CR 2) n, CO(CR 2) n, (CR 2) n, CO(CR 2) mO(CR 2) n, CO(CR 2) mNH(CR 2) n, CO(CH 2) nCO, COCHR 6>CHR 7>, C(=S)O(CR 2) n, CO(CRR 4>)(CR 2) n, COO(CRR 4>), (CRR 4>)(CR 2) n, S(O) qCR=CR, COCR=CR, (CR 2) mCO, CONH(CR 2) mCRR 4>or (CR 2) mCONR; R 4> : COOR 5>, Ar 2>, (CR 2) nNR 2, OH, NRCOOR 8>or NRCOOA; R 6>R 7> : (CH 2) 1 - 4; R 8> : phenyl, naphthyl or fluorenyl; R : H or optionally branched 1-6C alkyl; W 1> : Ar 1>or Het; Ar 1> : phenyl, indanyl, naphthyl or biphenyl (unsubstituted or 1-3 times substituted by hal, A, (CR 2) nOR, O(CR 2) n, Ar 2>, (CR 2) nNR 2, SR, NO 2, CN, COOR, CONR 2, NRCOA, NRSO 2A, SO 2NR 2, S(O) qA, CO-Het, (CR 2) nHet, O(CR 2) nNR 2, O(CR 2) nHet, NHCOOA, NHCONR 2, NHCOO(CR 2) nNR 2, NHCOO(CR 2) nHet, CR5=CR 5>Ar 2>, SO 2Het, NHCONH(CR 2) nNR 2, NHCONH(CR 2) nHet, OCONH(CR 2) nNR 2, OCONH(CR 2) n-Het, CONR(CR 2) nNR 2, CONR(CR 2) nHet and/or COA); Het : mono-, di- or tri-nuclear optionally saturated or aromatic heterocycle with 1-4 N-, O- and/or S-atoms (unsubstituted or 1-3 times substituted by hal, A, (CR 2) nAr 2>, O(CR 2) nAr 2>, (CR 2) nOR, (CR 2) nNR 2, SR, NO 2, CN, COOR, CONR 2, NRCOA, NRSO 2A, SO 2NR 2, S(O) qA, CO-Het 1>, (CR 2)nHet 1>, O(CR 2) nNR 2, O(CR 2) nHet 1>, NHCOOA, NHCONR 2, NHCOO(CR 2) nNR 2, NHCOO(CR 2) nHet 1>, NHCONH(CR 2) n-NR 2, NHCONH(CR 2) nHet 1>, OCONH(CR 2) nNR 2, OCONH(CR 2) nHet 1>, CO-Het 1>, CHO, COA, =S, =NH, =NA and/or =O); Het 1> : mononuclear saturated heterocycle with 1-2 N- and/or O-atoms (1-2 times substituted by A, OA, OH, hal, and/or =O); AR 2> : phenyl (unsubstituted or 1-5 times substituted by hal, CN, A and/or (CR 2) nOR); A : optionally branched 1-10C alkyl (where 1-7 H atoms are substituted by OR, CN, NR 2, F and/or Cl, and/or one or two non-adjacent CH 2-groups are substituted by O, NH, S, SO, SO 2and/or CH=CH-groups), or cyclic 3-7C alkyl; hal : F, Cl, Br or I; m, p : 1-6; n : 0-8; and q : 0-2. An independent claim is included for the preparation of (I). [Image] [Image] ACTIVITY : Cytostatic; Antiarteriosclerotic; Ophthalmological; Antiinflammatory; Antiarthritic; Neuroprotective; Vasotropic; Vulnerary; Immunosuppressive. MECHANISM OF ACTION : Autotaxin inhibitor.