N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide | 1257214-59-7

• 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: N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide
• 英文别名: N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]cyclopropanecarbonyl}methanesulfonamide；N-{2-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]cyclopropanecarbonyl}methanesulfonamide；N-{1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarbonyl}methanesulfonamide；N-methylsulfonyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropane-1-carboxamide
• CAS: 1257214-59-7
• 化学式: C₁₇H₂₄BNO₅S
• 分子量: 365.258
• InChiKey: BJQLTAKNZXYNGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.09
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide 、 [3-(4-bromo-phenyl)-5-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate 、 palladium diacetate 作用下， 以 水 、 甲苯 为溶剂， 反应 4.0h， 生成 {3-[4'-(1-methanesulfonylaminocarbonyl-cyclopropyl)-biphenyl-4-yl]-5-methyl-3H-[1,2,3]triazol-4-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
• 作为产物：
  描述：

  1-(4-溴苯基)环丙甲酸 在 氯化亚砜 、 potassium acetate 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 mineral oil 为溶剂， 反应 22.33h， 生成 N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide
  参考文献：
  名称：

  LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS

  摘要：

  本文描述了一些对溶血磷脂酸受体具有拮抗作用的化合物。还描述了包括本文描述的化合物在内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，用于治疗依赖溶血磷脂酸或由溶血磷脂酸介导的疾病或病症。

  公开号：

  US20120258987A1

文献信息

• POLYCYCLIC COMPOUNDS AS LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
  申请人：CLARK Ryan

  公开号：US20110082164A1

  公开（公告）日：2011-04-07

  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.

  本文描述了一些作为赖氨酸磷脂酸受体拮抗剂的化合物。还描述了包括本文描述的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，用于治疗依赖或介导赖氨酸磷脂酸的疾病或病症。
• [EN] N-ARYLTRIAZOLE COMPOUNDS AS LPAR ANTAGONISTS<br/>[FR] COMPOSÉS N-ARYLTRIAZOLE UTILISÉS COMME ANTAGONISTES DE LPAR
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013189865A1

  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.

  提供以下公式(I)的化合物：以及 pharmaceutically 可接受的盐，其中取代基如说明书所述。这些化合物以及包含它们的药物组合物可用于治疗炎症性疾病和障碍，例如，例如，肺纤维化。
• [EN] N-ALKYLTRIAZOLE COMPOUNDS AS LPAR ANTAGONISTS<br/>[FR] COMPOSÉS N-ALKYLTRIAZOLE UTILISÉS COMME ANTAGONISTES DE LPAR
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013189864A1

  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...

  本文提供了式(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。这些化合物及含有它们的药物组合物对于治疗炎症性疾病和紊乱，例如肺纤维化等，是有用的...
• LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
  申请人：Seiders Thomas Jon

  公开号：US20120258987A1

  公开（公告）日：2012-10-11

  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.

  本文描述了一些对溶血磷脂酸受体具有拮抗作用的化合物。还描述了包括本文描述的化合物在内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，用于治疗依赖溶血磷脂酸或由溶血磷脂酸介导的疾病或病症。
• Polycyclic antagonists of lysophosphatidic acid receptors
  申请人：Amira Pharmaceuticals, Inc.

  公开号：US08058300B2

  公开（公告）日：2011-11-15

  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.

  本文介绍的是一些可以拮抗溶血磷脂酰肌酸受体的化合物。还介绍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联合治疗依赖或介导溶血磷脂酰肌酸的疾病或症状。