2-(1H-吲唑-5-氧基)乙酸 | 30226-16-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(1H-吲唑-5-氧基)乙酸
• 英文名称: 1H-indazol-5-yloxyacetic acid
• 英文别名: (5-Indazolyloxy)essigsaeure；Acetic acid, (1H-indazol-5-yloxy)-；2-(1H-indazol-5-yloxy)acetic acid
• CAS: 30226-16-5
• 化学式: C₉H₈N₂O₃
• 分子量: 192.174
• InChiKey: REHXIBSZUOFNEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-二甲基-苯磺酰胺 、 2-(1H-吲唑-5-氧基)乙酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以88%的产率得到2-((1H-indazol-5-yl)oxy)-N-((2,4-dimethylphenyl)sulfonyl)acetamide
  参考文献：
  名称：

  Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators

  摘要：

  Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.

  DOI：

  10.1021/acs.jmedchem.9b02094
• 作为产物：
  描述：

  1H-吲唑-5-醇 、 溴乙酸乙酯 在 potassium carbonate 、 sodium hydroxide 作用下， 以 丙酮 、 甲醇 为溶剂， 反应 19.0h， 以99%的产率得到2-(1H-吲唑-5-氧基)乙酸
  参考文献：
  名称：

  Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators

  摘要：

  Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.

  DOI：

  10.1021/acs.jmedchem.9b02094

文献信息

• Rho KINASE INHIBITORS
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1403255A1

  公开（公告）日：2004-03-31

  A compound represented by the formula (1): wherein R1-X- indicates that 1 to 4 R1-X- groups are present which may be the same or different,    the ring A is a saturated or unsaturated 5-membered heterocyclic ring,    X is a single bond, a group represented by the formula: -N(R3)-, -O- or -S-, or the like.    R1 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like,    R2 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like, and    R3 is a hydrogen atom, a substituted or unsubstituted alkyl group, or the like; a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug is a useful compound as a therapeutic agent for diseases for which Rho kinase is responsible.

  由式（1）代表的化合物： 其中 R1-X- 表示存在 1 至 4 个 R1-X- 基团，这些基团可以相同或不同、 环 A 是饱和或不饱和的五元杂环、 X 是单键、由式子表示的基团：-N(R3)-、-O- 或 -S- 或类似的基团。 R1 是氢原子、卤素原子、硝基、羧基、取代或未取代的烷基或类似基团、 R2 是氢原子、卤素原子、硝基、羧基、取代或未取代的烷基或类似物，以及 R3 是氢原子、取代或未取代的烷基或类似物； 所述化合物的原药或所述化合物或原药的药学上可接受的盐是一种有用的化合物，可作为治疗 Rho 激酶引起的疾病的药物。
• [EN] SELECTIVE NON-CYCLIC NUCLEOTIDE ACTIVATORS FOR THE CAMP SENSOR EPAC1<br/>[FR] ACTIVATEURS NUCLÉOTIDIQUES NON CYCLIQUES SÉLECTIFS POUR LE CAPTEUR DE CAMP EPAC 1
  申请人：UNIV TEXAS

  公开号：WO2021188728A9

  公开（公告）日：2022-08-11
• Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators
  作者：Pingyuan Wang、Urszula Luchowska-Stańska、Boy van Basten、Haiying Chen、Zhiqing Liu、Jolanta Wiejak、Padraic Whelan、David Morgan、Emma Lochhead、Graeme Barker、Holger Rehmann、Stephen J. Yarwood、Jia Zhou

  DOI：10.1021/acs.jmedchem.9b02094

  日期：2020.5.28

  Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.