| abstract |
This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof. The novel pharmaceutical compounds have the formula <CHEM> wherein: R<1> is hydrogen, C1-C10 alkyl, arylalkyl, alkoxycarbonyl or acyl; R<2> is hydrogen, C1-C6 alkyl, substituted alkyl, cycloalkyl, or arylalkyl; R<3> is CO2H, SO3H, CONHSO2R<8>, or a group of formula <CHEM> <CHEM> <CHEM> W is (CH2)n, S, SO, SO2; Y is CHR<7>, NR<4>, O, S, SO, or SO2; Z is NR<6>, CHR<7>, or CH; or W and Y together are HC=CH or C IDENTICAL C, or Y and Z together are HC=CH or C IDENTICAL C; R<4> is hydrogen, C1-C4 alkyl, phenyl, or acyl; R<5> is hydrogen, C1-C4 alkyl, CF3, phenyl, hydroxy, amino, bromo, iodo, or chloro; R<6> is acyl; R<7> is independently hydrogen, C1-C4 alkyl, phenyl, or substituted phenyl; R<8> is C1-C4 alkyl or tetrazole-5-yl; and n is 0, 1, or 2; provided that when Y is NR<4>, O, S, SO, or SO2, W is (CH2)n and Z is CHR<7> or CH; further provided that when W is S, SO, or SO2, Y is CHR<7>, Z is CHR<7> or CH, or Y and Z together are HC=CH or C IDENTICAL C; further provided that when W and Z are CH2, Y is not S; further provided that when W and Y together are HC=CH or C IDENTICAL C, Z is CHR<7>; or a pharmaceutically acceptable salt thereof. 1, |