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    • 10. 发明公开
    • MODULATORS OF CANNABINOID RECEPTORS
    • 大麻素受体的调节因子
    • EP2177503A1
    • 2010-04-21
    • EP09012361.3
    • 2005-02-21
    • UCL Business PLC
    • Okuyama, MasahiroBaker, DavidPryce, GarethSelwood, DavidVisintin, Cristina
    • C07C233/68C07C233/77C07C63/04C07C69/78A61K31/167A61K31/192A61K31/216A61K31/235
    • C07C235/42A61K31/165C07C69/76C07C69/78C07C233/11C07C233/65C07C233/66C07C233/69C07C235/34C07C235/78C07C235/84C07C237/32C07C237/38C07C237/42C07C255/41C07C255/44
    • The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof,

      wherein Z is OR 1 or NR 1 R 2 wherein each of R 1 and R 2 is independently H, or a hydrocarbyl group;X is an alkylene, alkenylene, or alkynylene group, each of which may be optionally substituted by one or more substituents selected from alkyl, COOH, CO 2 -alkyl, alkenyl, CN, NH 2 , hydroxy, halo, alkoxy, CF 3 and nitro;
      Y is a polar functional group selected from OH, NO 2 CN, COR 3 , COOR 3 , NR 3 R 4 , CONR 3 R 4 , SO 3 H, SO 2 -R 3 , SO 2 NR 3 R 4 and CF 3 , where each of R 3 and R 4 is independently H or a hydrocarbyl group;
      A is an aryl or heteroaryl group, each of which may be optionally substituted; and
      B is (CH 2 ) n where n is 0, 1, 2, 3, 4 or 5;

      with the proviso that:
      (i) when A is phenyl, n is 0, and Z is OH, X-Y is other than meta -C≡C-(CH 2 ) 2 CO 2 H, meta -C≡C-(CH 2 ) 2 OH, meta -C≡C-(CH 2 ) 2 CO 2 Me, meta- (CH 2 ) 4 CO 2 H, ortho -CH 2 CO 2 H, ortho -(CH 2 ) 2 CO 2 H and ortho -(CH 2 ) 4 CO 2 H; and
      (ii) when A is phenyl, n is 0, and Z is OMe, X-Y is other than meta -C≡C-(CH 2 ) 4 OH.
      Further aspects of the invention relate to the use of such compounds in the preparation of a medicament for the treatment of a muscular disorder, a gastrointestinal disorder, or for controlling spasticity or tremors.
    • 本发明涉及式I化合物或其药学上可接受的盐,其中Z为OR1或NR1R2,其中R1和R2各自独立地为H或烃基; X为亚烷基,亚烯基或亚炔基, 其各自可任选被一个或多个选自烷基,COOH,CO 2 - 烷基,烯基,CN,NH 2,羟基,卤素,烷氧基,CF 3和硝基的取代基取代; Y是选自OH,NO 2 CN,COR 3,COOR 3,NR 3 R 4,CONR 3 R 4,SO 3 H,SO 2 -R 3,SO 2 NR 3 R 4和CF 3的极性官能团,其中R 3和R 4各自独立地为H或烃基; A是芳基或杂芳基,它们中的每一个可以任选被取代; 并且B是(CH 2)n,其中n是0,1,2,3,4或5; 条件是:(i)当A为苯基,n为0且Z为OH时,XY不是间位C≡C-(CH 2)2 CO 2 H,间位C≡C-(CH 2)2 OH, C≡C-(CH2)2CO2Me,间 - (CH2)4CO2H,邻CH2CO2H,邻 - (CH2)2CO2H和邻 - (CH2)4CO2H; 和(ii)当A是苯基时,n是0,并且Z是OMe,X-Y不同于间位C≡C-(CH 2)4 OH。 本发明的其他方面涉及这些化合物在制备用于治疗肌肉疾病,胃肠疾病或用于控制痉挛状态或震颤的药物中的用途。