New S-phenyl-pyrimidine derivs. - useful as glutamate release and aspartate release inhibitors for treating CNS disorders

摘要

(A) The use of pyrimidine derivs. of formula (I), or their acid addn. salts in the prepn. of medicaments for treating or preventing, CNS diseases or disorders in mammals is new. In (I), R1 and R2= H, halo, OH, alkoxy, alkyl, alkylthio or NRaRb; Ra and Rb= H, alkyl, aryl or aralkyl; or NRaRb = cyclic gp. opt. substd. by 1 or more alkyl(s) and opt. contg. an additional heteroatom; R3= H, alkyl (opt. substd. by 1 or more halo), NH2, mono- or di-alkylamino, CN, NO2, halo, CONH2, OH, COOH, alkoxy, alkylthio, alkylthioalkyl, S(O)n alkyl, di(alkoxy)alkyl, C(R)=NOH, COR, COOR or CH2X; R= H or alkyl; X = OH, alkoxy, aryloxy, aralkoxy, halo, CN, NRaRb, S(O)n alkyl or SO2N(Rc)2; n= 1-2; Rc= H or alkyl; either (1) R4-R8= H, halo, alkyl, perhaloalkyl, CN, CONH2, COOH, COR, NO2, NH2, alkylsulphonylamino,, S(O)n alkyl, alkoxy or SO2N(Rc)2; or R4+R5 or R5+R6= CH=CH-CH=CH or (CH2)4; and R7= R8 = H; the N in the pyrimidine ring are opt. N-alkylated or in N-oxide form; alkyl= 1-6C; aryl= 6-10C. (B) (I) and their acid addn. salts are new when: (1) provided (a) at least one of R4-R8 is not H; and (b) when R1= R2=NH2 or R1= OH and R2= NH2, R3 = H or alkyl and R7= H then R4 and R5 = halo; (2) R7= halo, alkyl, perhaloalkyl, CN, NO2, NH2, alkylthio, S(O)n alkyl or SO2N(Rc)2; (3) R1= morpholino, piperazinyl, N-alkylpiperazinyl, dialkylamino, alkylamino or alkylthio; (4) R3= alkoxy, alkylthio, alkyl (opt. substd. by 1 or more halo) or CH2X; X= alkylthio, aryloxy, aralkoxy, alkoxy or OH; R4-R6= H, halo, perhaloalkyl, CN, NO2, NH2 or alkylthio; R7= halo, alkyl, perhaloalkyl, CN, NO2, NH2 or SO2N(Rc')2; Rc' = alkyl; R8 = H or halo; or (5) R3= alkoxy, aryloxy, aralkoxy or alkylthio.