(R)-1-phenylethyl 1H-imidazole-1-carboxylate | 1247028-03-0

• 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: (R)-1-phenylethyl 1H-imidazole-1-carboxylate
• 英文别名: (R)-1-Phenylethyl 1H-imidazole-1-carboxylate；[(1R)-1-phenylethyl] imidazole-1-carboxylate
• CAS: 1247028-03-0
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: RNUUYOMGXOSIDK-SNVBAGLBSA-N

物化性质

• 沸点：
  358.1±35.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-phenylethyl 1H-imidazole-1-carboxylate 、 2-(4-fluoro-2-methylphenyl)piperazine 以 二氯甲烷 、 乙腈 为溶剂， 反应 24.0h， 以180 mg的产率得到(1R)-1-phenylethyl 3-(4-fluoro-2-methylphenyl)-1-piperazinecarboxylate
  参考文献：
  名称：

  2-（S）-（4-氟-2-甲基苯基）哌嗪-1-甲酸[1-（R）-（（3,5-双-三氟甲基苯基）乙基]甲酰胺（视黄醇）的发现过程和药理特性有力，选择性和口服活性的NK 1受体拮抗剂。

  摘要：

  为了发现新的类似药物的NK 1受体拮抗剂，通过对相关的N-苯基哌嗪类似物进行适当的化学探索，鉴定了一系列新的适当取代的C-苯基哌嗪衍生物，其具体目的是最大程度地提高它们的体外亲和力并同时优化其药代动力学概况。在合成的化合物中，鉴定出2-（S）-（4-氟-2-甲基苯基）哌嗪-1-甲酸[1-（R）-（3,5-双三氟甲基苯基）乙基]甲酰胺（vestipitant）作为最强效和选择性的NK 1之一有史以来发现过的受体拮抗剂，表现出适当的药代动力学性质和体内活性。根据其临床前概况，选择该化合物作为候选药物。

  DOI：

  10.1021/jm900023b
• 作为产物：
  描述：

  (R)-(+)-1-苯基乙醇 、 N,N'-羰基二咪唑 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (R)-1-phenylethyl 1H-imidazole-1-carboxylate
  参考文献：
  名称：

  2-（S）-（4-氟-2-甲基苯基）哌嗪-1-甲酸[1-（R）-（（3,5-双-三氟甲基苯基）乙基]甲酰胺（视黄醇）的发现过程和药理特性有力，选择性和口服活性的NK 1受体拮抗剂。

  摘要：

  为了发现新的类似药物的NK 1受体拮抗剂，通过对相关的N-苯基哌嗪类似物进行适当的化学探索，鉴定了一系列新的适当取代的C-苯基哌嗪衍生物，其具体目的是最大程度地提高它们的体外亲和力并同时优化其药代动力学概况。在合成的化合物中，鉴定出2-（S）-（4-氟-2-甲基苯基）哌嗪-1-甲酸[1-（R）-（3,5-双三氟甲基苯基）乙基]甲酰胺（vestipitant）作为最强效和选择性的NK 1之一有史以来发现过的受体拮抗剂，表现出适当的药代动力学性质和体内活性。根据其临床前概况，选择该化合物作为候选药物。

  DOI：

  10.1021/jm900023b

文献信息

• [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。
• N-ARYLTRIAZOLE COMPOUNDS AS LPAR ANTAGONISTS
  申请人：Hoffmann-La Roche Inc,

  公开号：US20150133512A1

  公开（公告）日：2015-05-14

  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。这些化合物及含有它们的制药组合物可用于治疗炎症性疾病和疾病，例如肺纤维化。
• Discovery of Highly Selective and Orally Active Lysophosphatidic Acid Receptor-1 Antagonists with Potent Activity on Human Lung Fibroblasts
  作者：Yimin Qian、Matthew Hamilton、Achyutharao Sidduri、Stephen Gabriel、Yonglin Ren、Ruoqi Peng、Rama Kondru、Arjun Narayanan、Terry Truitt、Rachid Hamid、Yun Chen、Lin Zhang、Adrian J. Fretland、Ruben Alvarez Sanchez、Kung-Ching Chang、Matthew Lucas、Ryan C. Schoenfeld、Dramane Laine、Maria E. Fuentes、Christopher S. Stevenson、David C. Budd

  DOI：10.1021/jm301022v

  日期：2012.9.13

  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.
• Chemoselective Esterification and Amidation of Carboxylic Acids with Imidazole Carbamates and Ureas
  作者：Stephen T. Heller、Richmond Sarpong

  DOI：10.1021/ol1018882

  日期：2010.10.15

  Imidazole carbamates and ureas were found to be chemoselective esterification and amidation reagents. A wide variety of carboxylic acids were converted to their ester or amide analogues by a simple synthetic procedure in high yields
• On the reactivity of imidazole carbamates and ureas and their use as esterification and amidation reagents
  作者：Stephen T. Heller、Richmond Sarpong

  DOI：10.1016/j.tet.2011.09.057

  日期：2011.11

  The optimization, substrate scope, and mechanism of esterification and amidation of carboxylic acids mediated by imidazole-based reagents are discussed. The innate reactivity of carbonylimidazole reagents with a range of nucleophiles is also explored. New reagents developed for the synthesis of alpha,beta-unsaturated esters are described, as are reagents for the preparation of tertiary amides directly from carboxylic acids. (C) 2011 Elsevier Ltd. All rights reserved.