ethyl 1-(4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-biphenyl-4-yl)-cyclopropanecarboxylate | 1380587-40-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 1-(4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-biphenyl-4-yl)-cyclopropanecarboxylate
• 英文别名: 1-[4'-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester；ethyl 1-[4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]phenyl]cyclopropane-1-carboxylate
• CAS: 1380587-40-5
• 化学式: C₂₄H₂₉BO₄
• 分子量: 392.303
• InChiKey: AZEPGTNWUBWLNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.25
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-biphenyl-4-yl)-cyclopropanecarboxylate 在 potassium phosphate 、 palladium diacetate 、 三乙胺 、 lithium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 2.17h， 生成 1-{4'-[5-((1-(4-fluorophenyl)ethoxy)carbonylamino)-1-methyl-1H-pyrazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid
  参考文献：
  名称：

  Discovery of Highly Selective and Orally Active Lysophosphatidic Acid Receptor-1 Antagonists with Potent Activity on Human Lung Fibroblasts

  摘要：

  Lysophosphatidic acid is a class of bioactive phospholipid that mediates most of its biological effects through LPA receptors, of which six isoforms have been identified. The recent results from LPA1 knockout mice suggested that blocking LPA1 signaling could provide a potential novel approach for the treatment of idiopathic pulmonary fibrosis. Here, we report the design and synthesis of pyrazole- and triazole-derived carbamates as LPA1-selective and LPA1/3 dual antagonists. In particular, compound 2, the most selective LPA1 antagonist reported, inhibited proliferation and contraction of normal human lung fibroblasts (NHLF) following LPA stimulation. Oral dosing of compound 2 to mice resulted in a dose-dependent reduction of plasma histamine levels in a murine LPA challenge model. Furthermore, we applied our novel antagonists as chemistry probes and investigated the contribution of LPA1/2/3 in mediating the pro-fibrotic responses. Our results suggest LPA1 as the major receptor subtype mediating LPA-induced proliferation and contraction of NHLF.

  DOI：

  10.1021/jm301022v
• 作为产物：
  描述：

  ethyl 1-(4'-hydroxybiphenyl-4-yl)cyclopropanecarboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 ethyl 1-(4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-biphenyl-4-yl)-cyclopropanecarboxylate
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRAZOLE COMPOUNDS AS LPAR ANTAGONISTS
  [FR] COMPOSÉS DE PYRAZOLE SUBSTITUÉS UTILISÉS COMME ANTAGONISTES DE LPAR

  摘要：

  本文提供的是式(I)的化合物以及其药用盐，其中取代基如规范中所披露。这些化合物及含有它们的药物组合物对治疗炎症性疾病和紊乱，如肺纤维化等，具有用途。

  公开号：

  WO2013189862A1

文献信息

• [EN] LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS D'ACIDE LYSOPHOSPHATIDIQUE
  申请人：INTERMUNE INC

  公开号：WO2013025733A1

  公开（公告）日：2013-02-21

  Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.

  提供了化合物、制备这种化合物的方法、包含这种化合物的药物组合物和药物，以及使用这种化合物治疗、预防或诊断与一种或多种赖氨酸磷脂酸受体相关的疾病、紊乱或状况的方法。
• LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS AND THEIR USE IN THE TREATMENT FIBROSIS
  申请人：Seiders Thomas Jon

  公开号：US20130253004A1

  公开（公告）日：2013-09-26

  Described herein are compounds that are antagonists of lysophosphatidic receptor(s). Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists, alone and in combination with other compounds, for treating LPA-dependent or LPA-mediated conditions or diseases.

  本文描述了一些能够拮抗溶血磷脂酸受体的化合物。同时还描述了包括上述化合物的药物组合物和药物，在治疗LPA依赖性或LPA介导的病症或疾病方面，使用这些拮抗剂的方法，以及单独或与其他化合物组合使用的方法。
• Lysophosphatidic acid receptor antagonists and their use in the treatment fibrosis
  申请人：Seiders Thomas Jon

  公开号：US09272990B2

  公开（公告）日：2016-03-01

  Described herein are compounds that are antagonists of lysophosphatidic receptor(s). Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists, alone and in combination with other compounds, for treating LPA-dependent or LPA-mediated conditions or diseases.

  本文描述了一些是溶血磷脂酸受体拮抗剂的化合物。还描述了包括上述化合物的药物组合物和药物，以及使用这些拮抗剂的方法，单独或与其他化合物结合，用于治疗依赖于或介导溶血磷脂酸的疾病或病症。
• SUBSTITUTED PYRAZOLE COMPOUNDS AS LPAR ANTAGONISTS
  申请人：Hoffmann-La Roche Inc.

  公开号：US20150259295A1

  公开（公告）日：2015-09-17

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of inflammatory diseases and disorders such as, for example, pulmonary fibrosis

  本文提供了公式(I)的化合物，以及其药学上可接受的盐，其中取代基如规范中所披露的那样。这些化合物及其含有它们的制药组合物，可用于治疗炎症性疾病和疾患，例如肺纤维化。
• HALOGEN-SUBSTITUTED HETEROCYCLIC COMPOUND
  申请人：UBE INDUSTRIES, LTD.

  公开号：EP2940013B1

  公开（公告）日：2018-02-21