| 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 formulan n wherein: n R¹ is hydrogen, C₁-C₁₀ alkyl, arylalkyl, alkoxycarbonyl or acyl; n R² is hydrogen, C₁-C₆ alkyl, substituted alkyl, cycloalkyl, or arylalkyl; n R³ is CO₂H, SO₃H, CONHSO₂R⁸, or a group of formulan n n n W is (CH₂) n , S, SO, SO₂; n Y is CHR⁷, NR⁴, O, S, SO, or SO₂; n Z is NR⁶, CHR⁷, or CH; or n W and Y together are HC=CH or C≡C, or Y and Z together are HC=CH or C≡C; n R⁴ is hydrogen, C₁-C₄ alkyl, phenyl, or acyl; n R⁵ is hydrogen, C₁-C₄ alkyl, CF₃, phenyl, hydroxy, amino, bromo, iodo, or chloro; n R⁶ is acyl; n R⁷ is independently hydrogen, C₁-C₄ alkyl, phenyl, or substituted phenyl; n R⁸ is C₁-C₄ alkyl or tetrazole-5-yl; and n n is 0, 1, or 2; nprovided that when Y is NR⁴, O, S, SO, or SO₂, W is (CH₂) n and Z is CHR⁷ or CH; n further provided that when W is S, SO, or SO₂, Y is CHR⁷, Z is CHR⁷ or CH, or Y and Z together are HC=CH or C≡C; n further provided that when W and Z are CH₂, Y is not S; n further provided that when W and Y together are HC=CH or C≡C, Z is CHR⁷; n or a pharmaceutically acceptable salt thereof. |