4-isocyanatomethylbiphenyl | 56651-65-1

• 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: 4-isocyanatomethylbiphenyl
• 英文别名: 1-(Isocyanatomethyl)-4-phenylbenzene
• CAS: 56651-65-1
• 化学式: C₁₄H₁₁NO
• 分子量: 209.247
• InChiKey: ZIKUQABKGGSGJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-isocyanatomethylbiphenyl 在 4-二甲氨基吡啶 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 (4-{1-[(Biphenyl-4-ylmethyl)-carbamoyl]-3,3-diethyl-4-oxo-azetidin-2-yloxy}-phenyl)-acetic acid
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003
• 作为产物：
  描述：

  4-联苯乙酸 在 sodium azide 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 氯仿 、 水 、 丙酮 为溶剂， 反应 1.42h， 生成 4-isocyanatomethylbiphenyl
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003

文献信息

• Beta lactam compounds and their use as inhibitors of tryptase
  申请人：Bristol-Myers Squibb Co.

  公开号：US06335324B1

  公开（公告）日：2002-01-01

  Compounds of the formulas: are disclosed. These compounds inhibit tryptase as well as other enzyme systems or are selective tryptase inhibitors and are useful as antiinflammatory agents particularly in the treatment of chronic asthma.

  这些化合物的结构式已被披露。这些化合物抑制色胺酸蛋白酶以及其他酶系统，或者是选择性色胺酸蛋白酶抑制剂，并且在特别是治疗慢性哮喘方面作为抗炎药物是有用的。
• Design and synthesis of uracil urea derivatives as potent and selective fatty acid amide hydrolase inhibitors
  作者：Yan Qiu、Jie Ren、Hongwei Ke、Yang Zhang、Qi Gao、Longhe Yang、Canzhong Lu、Yuhang Li

  DOI：10.1039/c7ra02237a

  日期：——

  picomolar FAAH inhibitors (4c, IC50 = 0.3 ± 0.05 nM; 4d, IC50 = 0.8 ± 0.1 nM) were developed. Compound 4c inhibited FAAH in a rapid, selective, noncompetitive, and irreversible pattern. This study provides several highly potent and selective FAAH inhibitors and an optimized chemical scaffold for the development of FAAH inhibitors. We anticipate that these FAAH inhibitors will enable new possibilities in

  脂肪酸酰胺水解酶（FAAH）是参与内源性大麻素（尤其是anandamide）生物降解的关键酶之一。FAAH的药理学阻断作用可恢复内源性大麻素的水平，从而在治疗炎症，抑郁和多发性硬化症方面提供治疗益处。在这项研究中，设计并合成了一系列尿嘧啶脲衍生物作为FAAH抑制剂。N-己基-2,4-二氧代-3,4-二氢嘧啶-1（2 H）-羧酰胺（1a的C5位置和侧链的结构修饰）导致FAAH抑制剂具有更高的效能和选择性。结构-活性关系（SAR）研究表明，C5吸电子取代基优选具有最佳效能，但不具有选择性，而用苯基烷基基团或联苯基取代烷基链可显着提高抑制效力和对FAAH的选择性。开发了两种高效的皮摩尔FAAH抑制剂（4c，IC 50 = 0.3±0.05 nM; 4d，IC 50 = 0.8±0.1 nM）。化合物4c以快速，选择性，非竞争性和不可逆的方式抑制FAAH。这项研究提供了几种高效和选择性的FAAH抑
• NON-NUCLEOSIDE ANTI-HEPACIVIRUS AGENTS AND USES THEREOF
  申请人：Boyd A. Vincent

  公开号：US20070021434A1

  公开（公告）日：2007-01-25

  The present dislcosure provides amide-based, non-nucleoside compounds having antiviral activity against Hepacivirus, such as hepatitis C virus (HCV), methods and intermediates for synthesizing such compounds, and methods of using the compounds in a variety of contexts, including in the treatment and prevention of viral infections. The present dislcosure also provides methods for identifying amide-based, non-nucleoside compounds having antiviral activity.

  本公开提供了基于酰胺的非核苷类化合物，具有抗Hepacivirus活性，例如丙型肝炎病毒（HCV），合成这类化合物的方法和中间体，以及在各种情境中使用这些化合物的方法，包括在治疗和预防病毒感染中的应用。本公开还提供了识别具有抗病毒活性的基于酰胺的非核苷类化合物的方法。
• COMPOSITIONS AND METHODS FOR TREATING HYPERPROLIFERATIVE DISEASE
  申请人：Cameron Dale Russell

  公开号：US20080171783A1

  公开（公告）日：2008-07-17

  The present disclosure provides amide-based, non-nucleoside compounds having an inhibitory activity against endogenous polymerases, such as polymerase alpha and polymerase gamma. This disclosure further provides uses of treating hyperproliferative diseases or disorders, such as benign or malignant neoplasms, and more specifically cancers that are sensitive to inhibition of polymerase alpha and polymerase gamma.

  本公开提供了基于酰胺的非核苷类化合物，具有对内源聚合酶（如聚合酶α和聚合酶γ）的抑制活性。本公开进一步提供了用于治疗过度增殖性疾病或疾病的用途，例如良性或恶性肿瘤，更具体地是对聚合酶α和聚合酶γ抑制敏感的癌症。
• Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase
  作者：Yan Qiu、Yang Zhang、Yuhang Li、Jie Ren

  DOI：10.3390/molecules21020229

  日期：——

  family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-carboxamide scaffold was confirmed as a novel template for FAAH inhibitors, based on which, a series of analogues had been prepared for an initial structure-activity relationship (SAR) study. Most of the synthesized compounds displayed moderate

  脂肪酸酰胺水解酶 (FAAH) 是一种细胞内丝氨酸酶，参与信号脂质脂肪酸乙醇酰胺家族的生物降解，具有神经保护、抗炎和镇痛作用。在本研究中，共轭 2,4-dioxo-pyrimidine-1-carboxamide 支架被确认为 FAAH 抑制剂的新模板，在此基础上，已经制备了一系列用于初始构效关系 (SAR) 的类似物学习。大多数合成的化合物显示出中等至显着的 FAAH 抑制效力。其中，化合物 11 和 14 显示出比其他化合物更好的活性，IC50 值为 21 和 53 nM。SAR 分析表明 2,4-dioxopyrimidine-1-carboxamides 代表了一类新型的 FAAH 强效抑制剂，尿嘧啶环上的取代或 N 端基团的取代可能有利于抑制效力。选定的此类化合物可用作进一步研究的有用母体分子。