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    • 61. 发明公开
    • Substituted dipeptide amides
    • 取代二哌啶酰胺。
    • EP0212550A2
    • 1987-03-04
    • EP86111143.3
    • 1986-08-12
    • G.D. Searle & Co.
    • Hansen, Donald Willis, Jr.Pilipauskas, Daniel RichardClare, Michael
    • C07K5/06A61K37/02
    • C07D333/48A61K38/00C07D333/20C07D333/38C07D335/02C07K5/06078
    • The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula:
      and the pharmaceutically acceptable acid addition salts thereof wherein R¹ is hydrogen, lower alkyl, hydroxy, lower alkoxy, -O(CH₂) n phenyl with the phenyl optionally substituted by halogen, -NO₂, -CN, -NH₂ or lower alkyl wherein n is 1 to 4; R² and R³ represent lower alkyl, halogen, or lower alkoxy, or either one of R² or R³ is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R⁴, R⁵, R⁶, and R⁹ may be the same or different and represent hydrogen, lower alkyl, cycloalkyl having 3 to 8 carbons, unsaturated lower alkyl, or -(CH₂) m cycloalkyl with the cycloalkyl having 3 to 8 carbons and m is 1 to 4; R 10 is hydrogen or -(CH₂) p phenyl or with the phenyl optionally substituted with -NH₂, -OH, halogen, -NO₂, or lower alkyl or -(CH₂) p thienyl wherein p is 1 to 4; one of R⁷ or R⁸ is -(CH₂) f -S(O) z -(CH₂) q -CH₃ where f is 1 to 3 and q is 0 to 3, z is 0, 1 or 2 and the other is hydrogen or lower alkyl, or R⁷ and R⁸ together with carbon w is
      where x and y are independently 1 to 3 and z is 0, or 2. V represents an asymmetric carbon that may be recemic or have the D or L configuration; W represents an asymmetric carbon when R⁷ and R⁸ are not the same that may be recemic or have the D or L configuration.
      The compounds of this invention are useful as analgesic and/or antihypertensive agents.
    • 本发明涉及下式的新型取代的酪氨酰丙氨酸二肽酰胺:其中R 1是氢,低级烷基,羟基,低级烷氧基,-O(CH 2)n苯基与苯基 任选地被卤素,-NO 2,-CN,-NH 2或其中n为1至4的低级烷基取代; R 2和R 3代表低级烷基,卤素或低级烷氧基,R 2或R 3中的任一个是氢,另一个是低级烷基,低级烷氧基或卤素; R 4,R 5,R 6和R 9可以相同或不同,表示氢,低级烷基,具有3-8个碳的环烷基,不饱和低级烷基或 - (CH 2)m环烷基 环烷基具有3至8个碳原子,m为1至4; R 10为氢或 - (CH 2)p苯基或与-NH 2,-OH,卤素,-NO 2或低级烷基或 - (CH 2)p噻吩基取代的苯基,其中p为1至4; R 7或R 8中的一个为 - (CH 2)f S(O)z - (CH 2)q -CH 3,其中f为1至3,q为0至3,z为0,1或2,且 另一个是氢或低级烷基,或R 7和R 8与碳w一起是,其中x和y独立地为1〜3,z为0或2.V表示可以是 接收或具有D或L配置; 当R 7和R 8不同时,W表示不对称碳,可以是可接受的或具有D或L构型。 本发明的化合物可用作镇痛和/或抗高血压药。