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    • 9. 发明公开
    • Phenylalanine derivative and proteinase inhibitor
    • 苯丙氨酸蛋白酶抑制剂冯蛋白酶。
    • EP0284632A1
    • 1988-10-05
    • EP87104690.0
    • 1987-03-30
    • Okamoto, ShosukeSHOWA DENKO KABUSHIKI KAISHA
    • Okamoto, ShosukeOkada, YoshioOkunomiya, AkikoNaito, Taketoshi SHOWA DENKO KABUSHIKI KAISHAKimura, Yoshio SHOWA DENKO KABUSHIKI KAISHAYamada, Morihiko SHOWA DENKO KABUSHIKI KAISHAOhno, Norio SHOWA DENKO KABUSHIKI KAISHAKatsuura, Yasuhiro SHOWA DENKO KABUSHIKI KAISHANojima, Hiroshi SHOWA DENKO KABUSHIKI KAISHAShishikura, Takashi SHOWA DENKO KABUSHIKI KAISHA
    • C07C233/65C07C233/67C07C233/76C07C233/77C07C233/81C07C233/57C07D213/75C07D213/80C07D213/643C07D213/30
    • C07D213/643C07D211/60C07D211/62C07D213/75C07D213/80C07D233/88C07D239/42C07D257/06C07D277/46C07D295/185
    • A phenylalanine derivative having the formula (I):
      wherein A represents (a) H 2 N-, (b)
      or
      B represents (a)
      (b)
      or
      wherein m is 0, 1, or 2 and n is 3, 4, or 5;

      X represents (a) hydroxy, (b) nitro, (c) amino, (d) phenoxy which may be substituted with (i) halogen or (ii) nitro, (e) C 1 -C 4 alkyloxy which may be substituted with (i) phenyl or (ii) benzoyl, (f) benzoyl, (g) pyridyloxy which may be substituted with (i) halogen or (ii) nitro, or (h) C 1 -C 4 alkyl which may be substituted with halogen;
      Y represents
      or -OR 3 wherein
      R 1 and R 2 are independently (a) hydrogen, (b) phenyl which may be substituted with (i) benzoyl, (ii) C 1 -C 4 alkylcarbonyl, (iii) C 1 -C 4 alkyl which may be further substituted with C 1 -C 4 alkoxycarbonyl or hydroxycarbonyl, (iv) C 2 -Cs alkenyl which may be further substituted with hydroxycarbonyl or C 1 -C 4 alkoxycarbonyl, (v) C 1 -C 4 alkoxycarbonyl, or (vi) amidino, (c) pyridyl which may be substituted with halogen or carboxyl (d) imidazolyl, (e) pyrimidyl, (f) tetrazolyl, (g) thiazolyl which may be substituted with C,-C 4 alkyl which may be further substituted with C 1 -C 4 alkoxycarbonyl, (h) C 1 -C 6 alkyl which may be substituted with C 1 -C 4 alkoxy, C 1 -C 4 alkoxycarbonyl, phenyl, or benzoyl, (i) C S -C 7 cycloalkyl which may be substituted with C 1 -C 4 alkoxycarbonyl or (j) R' and R 2 may form, with the nitrogen atom attached thereto, (i) pyperazyl which may be substituted on the nitrogen atom with C 1 -C 4 alkyl which may be further substituted with phenyl, (ii) piperidino which may be substituted with carboxyl or C 1 -C 4 alkoxycarbonyl, (iii) pyrrolidyl which may be substituted with C 1 -C 4 alkoxycarbonyl, or (iv) morpholyl; and
      R 3 represents (a) hydrogen, (b) C 1 -C 6 alkyl which may be substituted with (i) C 1 -C 4 alkoxy, (ii) phenyl, or (iii) pyridyl, or (c) pyridyl; or a pharmaceutically acceptable acid salt thereof.

      This phenylalanine derivative is effective as a proteinase.
    • 具有式(I)的苯丙氨酸衍生物:其中m为0,1或2,n为3,4或5; X表示(a)羟基,(b)硝基,(c)氨基,(d)可被(i)卤素或(ii)硝基取代的苯氧基,(e)可被(i )苯基或(ii)苯甲酰基,(f)苯甲酰基,(g)可被(i)卤素或(ii)硝基取代的吡啶氧基,或(h)可被卤素取代的C 1 -C 4烷基; Y表示或-OR 3,其中R 1和R 2独立地为(a)氢,(b)可被(i)苯甲酰基取代的苯基,(ii)C 1 -C 4烷基羰基, (iii)可以被C1-C4烷氧基羰基或羟基羰基进一步取代的C1-C4烷基,(iv)可以被羟基羰基或C1-C4烷氧基羰基进一步取代的C2-C5烯基,(v)C1-C4烷氧基羰基或( vi)脒基,(c)可以被卤素或羧基取代的吡啶基(d)咪唑基,(e)嘧啶基,(f)四唑基,(g)可被可以被C 1 -C 4烷基取代的噻唑基, C 1 -C 4烷氧基羰基,(h)可被C 1 -C 4烷氧基取代的C 1 -C 6烷基,C 1 -C 4烷氧基羰基,苯基或苯甲酰基,(i)可被C 1 -C 4烷氧基羰基取代的C 5 -C 7环烷基或( j)R 1和R 2可以与其连接的氮原子形成,(i)可以被氮原子取代的可以被苯基进一步取代的C 1 -C 4烷基的哒嗪基,(ii) 可被羧基或C 1 -C 4烷氧基羰基取代的哌啶子基,(iii)可被C 1 -C 4烷氧基羰基取代的吡咯烷基,或(iv)吗啉基; (ⅰ)C 1 -C 4烷氧基,(ⅱ)苯基或(ⅲ)吡啶基或(c)吡啶基)取代的C 1 -C 6烷基, 或其药学上可接受的酸盐。 该苯丙氨酸衍生物作为蛋白酶有效。