acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester, salt with L-pyroglutamic acid | 862993-83-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester, salt with L-pyroglutamic acid
• 英文别名: acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester L-pyroglutamic acid；acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester L-pyroglutamate；acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoroethoxy)-4-methoxyphenyl]cyclohexyl ester L-pyroglutamate
• CAS: 862993-83-7
• 化学式: C₅H₇NO₃*C₁₇H₂₃F₂NO₄
• 分子量: 472.486
• InChiKey: AOUIDZVMCCBASP-CRWXAAGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  33.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  137.18
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester, salt with L-pyroglutamic acid 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 acetic acid (1RS,3RS,4RS)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester
  参考文献：
  名称：

  [EN] NOVEL DIFLUOROETHOXY-SUBSTITUTED HYDROXY-6-PHENYLPHENANTHRIDINES AND THEIR USE AS PDE4 INHIBITORS
  [FR] NOUVELLES HYDROXY-6-PHENYLPHENANTHRIDINES DIFLUOROETHOXY-SUBSTITUEES

  摘要：

  具有特定化学式(I)的化合物，其中R1、R2、R3、R31、R4、R5、R6和R7具有描述中指示的含义，是新颖有效的PDE4抑制剂。

  公开号：

  WO2005085203A1
• 作为产物：
  描述：

  acetic acid (1RS,3RS,4RS)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester 、 L-焦谷氨酸 以 异丙醇 为溶剂， 生成 acetic acid (1R,3R,4R)-4-amino-3-[3-(2,2-difluoro-ethoxy)-4-methoxy-phenyl]-cyclohexyl ester, salt with L-pyroglutamic acid
  参考文献：
  名称：

  Novel isoamido-substituted hydroxy-6-phenylphenanthridines

  摘要：

  具有规定说明中提供的定义的取代基的化合物，其分子式为I，是新颖且有效的PDE4抑制剂。

  公开号：

  US20070191414A1

文献信息

• [EN] NOVEL GUANIDINYL-SUBSTITUTED HYDROXY-6-PHENYLPHENENTHRIDINES AS EFFECTIVE PHOSPHODIESTERASE (PDE) 4 INHIBITORS<br/>[FR] NOUVEAUX HYDROXY-6-PHENYLPHENENTHRIDINES A SUBSTITUTION GUANIDINYLE EFFICACES EN TANT QU'INHIBITEURS DE LA PHOSPHODIESTERASE (PDE) 4
  申请人：ALTANA PHARMA AG

  公开号：WO2005077906A1

  公开（公告）日：2005-08-25

  Compounds of a certain formula (1), in which R1, R2, R3, R31, R4, R5, R6 and R7 have the meanings indicated in the description, are novel effective PDE4 inhibitors in which R7 is a radical of formulae (a), (b), (c) or (d).

  某种化学式（1）的化合物中，其中R1、R2、R3、R31、R4、R5、R6和R7具有描述中指示的含义，是一种新颖有效的PDE4抑制剂，其中R7是化学式（a）、（b）、（c）或（d）的基团。
• [EN] NOVEL HYDROXY-6-HETEROARYLPHENANTHRIDINES AND THEIR USE AS PDE4 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE HYDROXY-6-HÉTÉROARYLPHÉNANTHRIDINE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2005085225A1

  公开（公告）日：2005-09-15

  Compounds of formula (I), in which R1 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy, R2 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together are a 1-2C-alkylenedioxy group, R3 is hydrogen or 1-4C-alkyl, R31 is hydrogen or 1-4C-alkyl, either, in a first embodiment (embodiment a) according to the present invention, R4 is -O-R41, in which R41 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or completely or predominantly fluorine-substituted 1-4C-alkyl, and R5 is hydrogen or 1-4C-alkyl, or, in a second embodiment (embodiment b) according to the present invention, R4 is hydrogen or 1-4C-alkyl, and R5 is -O-R51, in which R51 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or completely or predominantly fluorine-substituted 1-4C-alkyl, Har is optionally substituted by R6 and/or R7 and/or R8, and is a 5- to 10-membered monocylic or fused bicyclic unsaturated or partially saturated heteroaryl radical comprising 1 to 4 heteroatoms selected independently from the group consisting of oxygen, nitrogen and sulfur, are novel effective PDE4 inhibitors.

  公式（I）中的化合物，其中R1是羟基，1-4C-烷氧基，3-7C-环氧基，3-7C-环烷基甲氧基，2,2-二氟乙氧基，或完全或主要氟代的1-4C-烷氧基，R2是羟基，1-4C-烷氧基，3-7C-环氧基，3-7C-环烷基甲氧基，2,2-二氟乙氧基，或完全或主要氟代的1-4C-烷氧基，或者R1和R2一起是1-2C-烷二氧基基团，R3是氢或1-4C-烷基，R31是氢或1-4C-烷基，在本发明的第一实施例（实施例a）中，R4是-O-R41，其中R41是氢，1-4C-烷基，1-4C-烷氧基-1-4C-烷基，羟基-2-4C-烷基，1-7C-烷基羰基，或完全或主要氟代的1-4C-烷基，而R5是氢或1-4C-烷基，或者在本发明的第二实施例（实施例b）中，R4是氢或1-4C-烷基，而R5是-O-R51，其中R51是氢，1-4C-烷基，1-4C-烷氧基-1-4C-烷基，羟基-2-4C-烷基，1-7C-烷基羰基，或完全或主要氟代的1-4C-烷基，Har可选地由R6和/或R7和/或R8取代，并且是包含1至4个异原子（独立选择自氧、氮和硫组成的）的5-到10-成员单环或融合的双环不饱和或部分饱和杂环基团，是新颖的有效PDE4抑制剂。
• [EN] NOVEL THIO-CONTAINING HYDROXY-6-PHENYLPHENANTHRIDINES AND THEIR USE AS PDE4 INHIBITORS<br/>[FR] NOUVELLES HYDROXY-6-PHENYLPHENANTHRIDINES CONTENANT THIO ET LEUR UTILISATION COMME INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2005087744A1

  公开（公告）日：2005-09-22

  Compounds of formula (I) in which R1 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or com­pletely or predominantly fluorine-substituted 1-4C-alkoxy, R2 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or com­pletely or predominantly fluorine-substituted 1-4C-alkoxy, or in which R 1 and R2 together are a 1-2C-alkylenedioxy group, R3 is hydrogen or 1-4C-alkyl, R31 is hydrogen or 1-4C-alkyl, either, in a first embodiment (embodiment a) according to the present invention, R4 is -0-R41, in which R41 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or com­ pletely or predominantly fluorine-substituted 1-4C-alkyl, and R5 is hydrogen or 1-4C-alkyl, or, in a second embodiment (embodiment b) according to the present invention, R4 is hydrogen or 1-4C-alkyl, and R5 is -O-R51, in which R51 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or com­ pletely or predominantly fluorine-substituted 1-4C-alkyl, R6 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy, R7 is -S(O)2N(R8)R9, -A-N(R10)S(0)2-R11, or -S(O)nR12, A is a bond or 1-4C-alkylene, are novel effective PDE4 inhibitors.

  式（I）中的化合物，其中R1是羟基，1-4C-烷氧基，3-7C-环烷氧基，3-7C-环烷基甲氧基，2,2-二氟乙氧基，或完全或主要为氟取代的1-4C-烷氧基，R2是羟基，1-4C-烷氧基，3-7C-环烷氧基，3-7C-环烷基甲氧基，2,2-二氟乙氧基，或完全或主要为氟取代的1-4C-烷氧基，或者R1和R2一起是1-2C-烷二氧基基团，R3是氢或1-4C-烷基，R31是氢或1-4C-烷基，在本发明的第一实施例（实施例a）中，R4是-0-R41，其中R41是氢，1-4C-烷基，1-4C-烷氧基-1-4C-烷基，羟基-2-4C-烷基，1-7C-烷基羰基，或完全或主要为氟取代的1-4C-烷基，而R5是氢或1-4C-烷基，或者在本发明的第二实施例（实施例b）中，R4是氢或1-4C-烷基，而R5是-O-R51，其中R51是氢，1-4C-烷基，1-4C-烷氧基-1-4C-烷基，羟基-2-4C-烷基，1-7C-烷基羰基，或完全或主要为氟取代的1-4C-烷基，R6是氢，卤素，1-4C-烷基或1-4C-烷氧基，R7是-S(O)2N(R8)R9，-A-N(R10)S(0)2-R11，或-S(O)nR12，A是键或1-4C-烷基，是新型有效的PDE4抑制剂。
• [EN] NOVEL AMIDO-SUBSTITUTED HYDROXY-6-PHENYLPHENANTHRIDINES AND THEIR USE AS PDE4 INHIBITORS<br/>[FR] NOUVEAUX HYDROXY-6-PHENYLPHENANTHRIDINES AMIDO-SUBSTITUES ET LEUR UTILISATION COMME INHIBITEURS DE PDE4
  申请人：ALTANA PHARMA AG

  公开号：WO2005087745A1

  公开（公告）日：2005-09-22

  Compounds of formula (I) in which R1 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or com­ pletely or predominantly fluorine-substituted 1-4C-alkoxy, R2 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3.7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or com­ pletely or predominantly fluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together are a 1-2C-alkylenedioxy group, R3 is hydrogen or 1-4C-alkyl, R31 is hydrogen or 1-4C-alkyl, either, in a first embodiment (embodiment a) according to the present invention, R4 is -0-R41, in which R41 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or com­ pletely or predominantly fluorine-substituted 1-4C-alkyl. and R5 is hydrogen or 1-4C-alkyl, or, in a second embodiment (embodiment b) according to the present invention, R4 is hydrogen or 1-4C-alkyl, and R5 is -0-R51, in which R51 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyt, or com­ pletely or predominantly fluorine-substituted 1-4C-alkyl, R6 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy, either, in a first aspect (aspect 1) according to the present invention, R7 is -N(R8)R9, or, in a second aspect (aspect 2) according to the present invention, R7 is -NH-N(R18)R19, are novel effective PDE4 inhibitors.

  化学式（I）中的化合物，其中R1是羟基，1-4C-烷氧基，3-7C环烷氧基，3-7C环烷基甲氧基，2,2-二氟乙氧基，或完全或主要是氟取代的1-4C烷氧基，R2是羟基，1-4C烷氧基，3-7C环烷氧基，3.7C环烷基甲氧基，2,2-二氟乙氧基，或完全或主要是氟取代的1-4C烷氧基，或者R1和R2一起是1-2C烷二氧基基团，R3是氢或1-4C烷基，R31是氢或1-4C烷基，在根据本发明的第一实施例（实施例a）中，R4是-0-R41，其中R41是氢，1-4C烷基，1-4C烷氧基-1-4C烷基，羟基-2-4C烷基，1-7C烷基羰基，或完全或主要是氟取代的1-4C烷基。R5是氢或1-4C烷基，或者在根据本发明的第二实施例（实施例b）中，R4是氢或1-4C烷基，而R5是-0-R51，其中R51是氢，1-4C烷基，1-4C烷氧基-1-4C烷基，羟基-2-4C烷基，1-7C烷基羰基，或完全或主要是氟取代的1-4C烷基，R6是氢，卤素，1-4C烷基或1-4C烷氧基，根据本发明的第一方面（方面1）中，R7是-N（R8）R9，或者根据本发明的第二方面（方面2）中，R7是-NH-N（R18）R19，是新型有效的PDE4抑制剂。