4-(5-(5-(3,4-Difluorophenylamino)-1,3,4-oxadiazole-2-carboxamido)-Pyridin-2-yloxy)benzoic acid | 1124173-02-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(5-(5-(3,4-Difluorophenylamino)-1,3,4-oxadiazole-2-carboxamido)-Pyridin-2-yloxy)benzoic acid
• 英文别名: 4-[5-[[5-(3,4-difluoroanilino)-1,3,4-oxadiazole-2-carbonyl]amino]pyridin-2-yl]oxybenzoic acid
• CAS: 1124173-02-9
• 化学式: C₂₁H₁₃F₂N₅O₅
• 分子量: 453.362
• InChiKey: UYIHXSMNIGWVLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 4-(5-(5-(3,4-Difluorophenylamino)-1,3,4-oxadiazole-2-carboxamido)-Pyridin-2-yloxy)benzoic acid
  参考文献：
  名称：

  设计和合成一系列新型的环己氧基-吡啶基衍生物作为二酰基甘油酰基转移酶的抑制剂1 †

  摘要：

  从临床候选药物AZD3988开发了一系列新型的强力二酰基甘油酰基转移酶1抑制剂。用取代的氧连接侧链取代苯基环己基-乙酸根侧链，以引入形状和极性的变化，降低亲脂性，并用内部氢键受体掩盖氢键供体，从而提高了溶解度，未结合的清除率和相对于丙二醇的优异选择性相关酶酰基辅酶A：胆固醇酰基转移酶1.化合物4和化合物28的小分子晶体结构比较描述。该系列化合物具有良好的ADMET性质，并在大鼠口服脂质耐受性试验中使血浆血浆甘油三酯水平降低，并依赖于暴露。

  DOI：

  10.1039/c2md20187a

文献信息

• CHEMICAL COMPOUNDS 979
  申请人：Birch Alan Martin

  公开号：US20110092547A1

  公开（公告）日：2011-04-21

  Compounds of formula (I), or pharmaceutically-acceptable salts and/or pro-drugs thereof, which inhibit acetyl CoA(acetyl coenzyme A):diacylglycerol acyltransferase (DGAT1) activity are provided, wherein n is 0 to 3; p is 0 or 1; q is 0 to 2; R 1 and R 2 are, for example, independently fluoro, chloro, bromo, cyano or (1-4C)alkyl; X is —O—, —S— or —NRa— wherein Ra is hydrogen or (1-4C)alkyl; R A1 and R A2 are, for example, independently hydrogen or (1-4C)alkyl; Ring A is a di-linked ring or ring system chosen from (4-6C)cycloalkane, (7-10C)bicycloalkane and (8-12C)tricycloalkane each optionally substituted, for example, by one substituent selected from (1-4C)alkyl, (1-4C)alkoxy and (1-4C)alkoxy(1-4C)alkyl; or Ring A is phenylene optionally substituted, for example, by up to four substituents selected from fluoro, chloro, bromo, cyano, (1-4C)alkyl, (1-4C)alkoxy and (1-4C)alkoxy( 1 -4C)alkyl; together with processes for their preparation, pharmaceutical compositions containing them and their use as medicaments.

  提供公式（I）的化合物，或其药学上可接受的盐和/或前药，其抑制乙酰辅酶A：二酰基甘油酰基转移酶（DGAT1）活性，其中n为0至3；p为0或1；q为0至2；R1和R2例如独立地为氟、氯、溴、氰或（1-4C）烷基；X为—O—、—S—或—NRa—，其中Ra为氢或（1-4C）烷基；RA1和RA2例如独立地为氢或（1-4C）烷基；环A为二联环或环系统，选择自（4-6C）环烷、（7-10C）双环烷和（8-12C）三环烷，每个环可选地被一个取代基取代，所述取代基选择自（1-4C）烷基、（1-4C）烷氧基和（1-4C）烷氧基（1-4C）烷基；或环A为苯环，可选地被多达四个取代基取代，所述取代基选择自氟、氯、溴、氰、（1-4C）烷基、（1-4C）烷氧基和（1-4C）烷氧基（1-4C）烷基；以及它们的制备过程、含有它们的药物组合物和它们作为药物的用途。
• [EN] CHEMICAL COMPOUNDS 979<br/>[FR] COMPOSÉS CHIMIQUES 979
  申请人：ASTRAZENECA AB

  公开号：WO2009024821A2

  公开（公告）日：2009-02-26

  Compounds of formula (I), or pharmaceutically-acceptable salts and/or pro-drugs thereof, which inhibit acetyl CoA(acetyl coenzyme A):diacylglycerol acyltransferase (DGAT1) activity are provided, wherein n is 0 to 3; p is 0 or 1; q is 0 to 2; R1and R2are, for example, independently fluoro, chloro, bromo, cyano or (1-4C)alkyl; X is -O-, -S- or -NRa- wherein Ra is hydrogen or (1-4C)alkyl; RA1 and RA2 are, for example, independently hydrogen or (1-4C)alkyl; Ring A is a di-linked ring or ring system chosen from (4-6C)cycloalkane, (7- 10C)bicycloalkane and (8-12C)tricycloalkane each optionally substituted, for example, by one substituent selected from (1-4C)alkyl, (1-4C)alkoxy and (1-4C)alkoxy(1-4C)alkyl; or Ring A is phenylene optionally substituted, for example, by up to four substituents selected from fluoro, chloro, bromo, cyano, (1-4C)alkyl, (1-4C)alkoxy and (1- 4C)alkoxy(1-4C)alkyl; togetherwith processes for their preparation, pharmaceutical compositions containing them and their use as medicaments.
• Design and synthesis of a novel series of cyclohexyloxy-pyridyl derivatives as inhibitors of diacylglycerol acyl transferase 1
  作者：Alleyn T. Plowright、Peter Barton、Stuart Bennett、Alan M. Birch、Susan Birtles、Linda K. Buckett、Roger J. Butlin、Robert D. M. Davies、Anne Ertan、Pablo Morentin Gutierrez、Paul D. Kemmitt、Andrew G. Leach、Per H. Svensson、Andrew V. Turnbull、Michael J. Waring

  DOI：10.1039/c2md20187a

  日期：——

  A novel series of potent diacylglycerol acyl transferase 1 inhibitors was developed from the clinical candidate AZD3988. Replacement of the phenyl cyclohexyl-ethanoate side chain with substituted oxy-linked side chains to introduce changes in shape and polarity, reduce lipophilicity and mask the hydrogen bond donors with internal hydrogen bond acceptors led to improvements in solubility, unbound clearance

  从临床候选药物AZD3988开发了一系列新型的强力二酰基甘油酰基转移酶1抑制剂。用取代的氧连接侧链取代苯基环己基-乙酸根侧链，以引入形状和极性的变化，降低亲脂性，并用内部氢键受体掩盖氢键供体，从而提高了溶解度，未结合的清除率和相对于丙二醇的优异选择性相关酶酰基辅酶A：胆固醇酰基转移酶1.化合物4和化合物28的小分子晶体结构比较描述。该系列化合物具有良好的ADMET性质，并在大鼠口服脂质耐受性试验中使血浆血浆甘油三酯水平降低，并依赖于暴露。