tert-butyl 2-(5-chloro-3-(4-hydroxyphthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetate | 881170-98-5

• 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: tert-butyl 2-(5-chloro-3-(4-hydroxyphthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetate
• 英文别名: tert-butyl 2-[5-chloro-2-methyl-3-(4-oxo-3H-phthalazin-1-yl)indol-1-yl]acetate
• CAS: 881170-98-5
• 化学式: C₂₃H₂₂ClN₃O₃
• 分子量: 423.899
• InChiKey: XYSFTWPIKHBDLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(5-chloro-3-(4-hydroxyphthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetate 在 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 2-(3-(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)-5-chloro-2-methyl-1H-indol-1-yl)acetic acid
  参考文献：
  名称：

  Diazine Indole Acetic Acids as Potent, Selective, and Orally Bioavailable Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents, 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.

  DOI：

  10.1021/jm300007n
• 作为产物：
  描述：

  1,4-二氯酞嗪 在 aluminum (III) chloride 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 tert-butyl 2-(5-chloro-3-(4-hydroxyphthalazin-1-yl)-2-methyl-1H-indol-1-yl)acetate
  参考文献：
  名称：

  INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS

  摘要：

  公开的是以下化合物的结构（I）：这些化合物可用作CRTH2受体的拮抗剂。还公开了含有化合物（I）的药物组合物以及利用化合物（I）治疗对抑制内源配体与CRTH2受体结合响应的疾病或疾病的用途。进一步描述了制备和使用这些化合物的方法。

  公开号：

  US20110105509A1

文献信息

• INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS
  申请人：Kaila Neelu

  公开号：US20110105509A1

  公开（公告）日：2011-05-05

  Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.

  公开的是以下化合物的结构（I）：这些化合物可用作CRTH2受体的拮抗剂。还公开了含有化合物（I）的药物组合物以及利用化合物（I）治疗对抑制内源配体与CRTH2受体结合响应的疾病或疾病的用途。进一步描述了制备和使用这些化合物的方法。
• Indole acetic acids exhibiting CRTH2 receptor antagonism and uses thereof
  申请人：Bennani L. Youssef

  公开号：US20060100425A1

  公开（公告）日：2006-05-11

  The invention relates to indole acetic acid compounds which function as antagonists of the CRTH2 receptor. The invention also relates to the use of these compounds to inhibit the binding of prostaglandin D 2 and its metabolites or certain thromboxane metabolites to the CRTH2 receptor and to treat disorders responsive to such inhibition.

  本发明涉及吲哚乙酸化合物，其作为CRTH2受体的拮抗剂。本发明还涉及使用这些化合物来抑制前列腺素D2及其代谢物或某些血栓素代谢物与CRTH2受体的结合，并治疗对此类抑制有响应的疾病。
• INDOLE ACETIC ACIDS EXHIBITING CRTH2 RECEPTOR ANTAGONISM AND USES THEREOF
  申请人：Bennani Youssef L.

  公开号：US20100016389A1

  公开（公告）日：2010-01-21

  The invention relates to indole acetic acid compounds which function as antagonists of the CRTH2 receptor. The invention also relates to the use of these compounds to inhibit the binding of prostaglandin D 2 and its metabolites or certain thromboxane metabolites to the CRTH2 receptor and to treat disorders responsive to such inhibition.

  本发明涉及吲哚乙酸类化合物，其作为CRTH2受体的拮抗剂。本发明还涉及使用这些化合物来抑制前列腺素D2及其代谢物或某些血栓素代谢物与CRTH2受体的结合，并治疗对此类抑制有反应的疾病。
• [EN] INDOLE ACETIC ACIDS EXHIBITING CRTH2 RECEPTOR ANTAGONISM AND USES THEREOF<br/>[FR] ACIDES INDOLE ACETIQUES ANTAGONISTES DU RECEPTEUR CRTH2 ET SES UTILISATIONS
  申请人：ATHERSYS INC

  公开号：WO2006034419A3

  公开（公告）日：2007-06-14
• EP1805171A4
  申请人：——

  公开号：EP1805171A4

  公开（公告）日：2009-05-13