| 摘要 |
Pyrimidine derivatives (I) are new. Pyrimidine derivatives of formula (I) and their acid addition salts are new: A : CW or CRfRg; B : a bond or CRhRi; X : O, S, NRk or CRmRn; D : CO or a bond; E : 2-10C alkylene with 0-2 nonadjacent C atoms replaced by O, S, SO, SO 2 or NRp, optionally containing a CO group and/or a cycloalkanediyl group and/or containing a double or triple bond; W : O or S; Z : a 5- to 7-membered carbocycle or heterocycle with 0-4 heteroatoms (N, O, S) optionally with 1-2 CO groups and/or 1-4 substituents R; R : optionally substituted 1-6C alkyl, CN, OR 1>, NR 2>R 3>, NO 2, SR 4>, SO 2R 4>, SO 2NR 2>R 3>, CONR 2>R 3>, COOR 6>, COR 6>, 1-4C haloalkoxy, 2-6C alkenyl, 2-6C alkynyl, 2-6C alkenyloxy, 2-6C alkynyloxy, 3-6C cycloalkyl, 3-6C cycloalkoxy or halo, or R+R = X'-Alk'-X"; X', X" : O or S; Alk' : 1-4C alkanediyl optionally substituted with 1-4 of alkyl or halo; J, Y : CH 2, CH 2CH 2 or CH 2CH 2CH 2; M : CH or N; M-Y : CH=C or CH 2CH=C; n : 0 or 1; Ra, Rb : optionally substituted 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl; 3-6C cycloalkyl, 4-10C bicycloalkyl or 6-10C tricycloalkyl, each optionally substituted with halo or 1-4C alkyl; halo, CN, OR 1>, NR 2>R 3>, NO 2, SR 4>, SO 2R 5>, SO 2NR 2>R 3>, CONR 2>R 3>, COOR 5>, COR 6>, OCOR 6>, 5- or 6-membered heterocyclyl with 1-3 heteroatoms (O, S, N) or phenyl, where phenyl and heterocyclyl are optionally substituted with 1-3 of 1-4C alkyl, 1-4C alkoxy, NR 2>R 3>, CN, 1-2C fluoroalkyl and halo; Rc : 1-4C alkyl; Rd, Re : H, halo, optionally substituted 1-6C alkyl, 3-6C cycloalkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkoxy, 3-6C cycloalkoxy, (3-6C)cycloalkyl(1-4C)alkoxy or optionally substituted phenyl, or Rd+Re = O or X'-Alk'-X", or Rd or Rd can form a pi bond with Rm, Rn or Rk; Rf, Rg : H, halo, optionally substituted 1-6C alkyl, 3-6C cycloalkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkoxy, 3-6C cycloalkoxy, (3-6C)cycloalkyl(1-4C)alkoxy, or Rf+Rg = X'-Alk'-X"; Rh, Ri : H, halo, optionally substituted 1-6C alkyl, 3-6C cycloalkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkoxy, 3-6C cycloalkoxy, (3-6C)cycloalkyl(1-4C)alkoxy; Rk, Rp : H, 1-4C alkyl, 1-6C alkoxy, 1-6C alkoxyalkyl, 1-6C alkylcarbonyl, 1-6C alkoxycarbonyl, phenylalkyl, phenylcarbonyl or phenoxycarbonyl, where phenyl is optionally substituted with 1-3 of 1-4C alkyl, 1-4C alkoxy, NR 2>R 3>, CN, 1-2C fluoroalkyl and halo; Rm, Rn : H, halo, optionally substituted 1-6C alkyl, 3-6C cycloalkyl, 2-6C alkenyl, 2-6C alkynyl, 1-6C alkoxy, 3-6C cycloalkoxy, (3-6C)cycloalkyl(1-4C)alkoxy; R 1>-R 6>H, optionally substituted 1-6C alkyl or optionally substituted phenyl, or R 3> is COR 7>, or NR 23> is a 5- or 6-membered heterocycle optionally containing another heteroatom (O, S, NR 8>); R 7>H, optionally substituted 1-4C alkyl or optionally substituted phenyl; R 8>H or 1-4C alkyl. [Image] - ACTIVITY : Neuroleptic; Antidepressant; Nephrotropic; Antimanic; Nootropic; Tranquilizer; Vasotropic; Antiparkinsonian; Anticonvulsant; Antiaddictive; Antismoking; Antialcoholic. - MECHANISM OF ACTION : Dopamine D3 receptor ligand. 1-(2-t-butyl-6-trifluoromethyl-4-pyrimid inyl)-4-(3-(2-oxo-3,4-dihydro-1(2H)-quinolinyl)propyl)-4-piperizinium chloride had a Ki of 3.43 nM is a dopamine D3 receptor affinity assay and 127 nM in a dopamine D2L receptor affinity assay. |
