2-methyl-4-phenyl-2H-pyrazol-3-yl-carbamic acid (R)-1-phenyl-ethyl ester | 1396006-74-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-methyl-4-phenyl-2H-pyrazol-3-yl-carbamic acid (R)-1-phenyl-ethyl ester
• 英文别名: [(1R)-1-phenylethyl] N-(2-methyl-4-phenylpyrazol-3-yl)carbamate
• CAS: 1396006-74-8
• 化学式: C₁₉H₁₉N₃O₂
• 分子量: 321.379
• InChiKey: QUWIZCMIURDWRW-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-4-phenyl-2H-pyrazol-3-yl-carbamic acid (R)-1-phenyl-ethyl ester 、 4-联苯硼酸 、 4-溴-1-甲基-1H-吡唑-5-羧酸甲酯 生成 (4-biphenyl-4-yl-2-methyl-2H-pyrazol-3-yl)-carbamic acid (R)-1-phenyl-ethyl ester
  参考文献：
  名称：

  SUBSTITUTED PYRAZOLE COMPOUNDS AS LPAR ANTAGONISTS

  摘要：

  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。

  公开号：

  US20150259295A1
• 作为产物：
  描述：

  苯硼酸 在 四(三苯基膦)钯 、 叠氮磷酸二苯酯 、 caesium carbonate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 15.0h， 生成 2-methyl-4-phenyl-2H-pyrazol-3-yl-carbamic acid (R)-1-phenyl-ethyl ester
  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

文献信息

• [EN] SUBSTITUTED PYRAZOLE COMPOUNDS AS LPAR ANTAGONISTS<br/>[FR] COMPOSÉS DE PYRAZOLE SUBSTITUÉS UTILISÉS COMME ANTAGONISTES DE LPAR
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013189862A1

  公开（公告）日：2013-12-27

  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。