1-fluoro-4-(3-isocyanatopropyl)benzene | 1082601-04-4

• 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: 1-fluoro-4-(3-isocyanatopropyl)benzene
• CAS: 1082601-04-4
• 化学式: C₁₀H₁₀FNO
• mdl: MFCD11592320
• 分子量: 179.194
• InChiKey: ZYDFHVBSJPIGGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,7-dichloro-3-[2-(naphthalen-2-ylmethylidene)hydrazinyl]indol-2-one 、 1-fluoro-4-(3-isocyanatopropyl)benzene 在 N-甲基吗啉 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  N-Acylpolyamine inhibitors of HDM2 and HDMX binding to p53

  摘要：

  Selective inhibition of protein-protein interactions important for cellular processes could lead to the development of new therapies against disease. In the area of cancer, overexpression of the proteins human double minute 2 (HDM2) and its homolog HDMX has been linked to tumor aggressiveness. Both HDM2 and HDMX bind to p53 and prevent cell cycle arrest or apoptosis in damaged cells. Developing a strategy to simultaneously prevent the binding of both HDM2 and HDMX to p53 is an essential feature of inhibitors to restore p53 activity in a number of different cancers. Inhibition of protein-protein interactions with synthetic molecules is an emerging area of research that requires new inhibitors tailored to mimic the types of interfaces between proteins. Our strategy to create inhibitors of protein-protein interactions is to develop a non-natural scaffold that may be used as a starting point to identify important molecular components necessary for inhibition. In this study, we report an N-acylpolyamine (NAPA) scaffold that supports numerous sidechains in a compact atomic arrangement. NAPAs were constructed by a series of reductive aminations between amino acid derivatives followed by acylation at the resulting secondary amine. An optimized NAPA was able to equally inhibit the association of both HDM2 and HDMX with p53. Our results demonstrate some of the challenges associated with targeting multiple protein-protein interactions involved in overlapping cellular processes. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.10.032
• 作为产物：
  描述：

  三光气 、 3-(4-氟-苯基)-丙胺 在 1,8-双二甲氨基萘 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-fluoro-4-(3-isocyanatopropyl)benzene
  参考文献：
  名称：

  [EN] SUBSTITUTED, SATURATED AND UNSATURATED N-HETEROCYCLIC CARBOXAMIDES AND RELATED COMPOUNDS FOR THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
  [FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS, SATURÉS ET INSATURÉS ET COMPOSÉS APPARENTÉS POUR LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX

  摘要：

  这项发明提供了替代的、饱和的和不饱和的N-杂环羧酰胺及相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗患者的医疗疾病，例如癌症、溶酶体贮积疾病、神经退行性疾病、炎症性疾病等的方法。

  公开号：

  WO2021055630A1

文献信息

• SUBSTITUTED, SATURATED AND UNSATURATED N-HETEROCYCLIC CARBOXAMIDES AND RELATED COMPOUNDS FOR THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
  申请人：Bial - R&D Investments, S.A.

  公开号：US20220380314A1

  公开（公告）日：2022-12-01

  The invention provides substituted, saturated and unsaturated N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.
• [EN] SUBSTITUTED, SATURATED AND UNSATURATED N-HETEROCYCLIC CARBOXAMIDES AND RELATED COMPOUNDS FOR THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS, SATURÉS ET INSATURÉS ET COMPOSÉS APPARENTÉS POUR LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：BIAL BIOTECH INVEST INC

  公开号：WO2021055630A1

  公开（公告）日：2021-03-25

  The invention provides substituted, saturated and unsaturated N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

  这项发明提供了替代的、饱和的和不饱和的N-杂环羧酰胺及相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗患者的医疗疾病，例如癌症、溶酶体贮积疾病、神经退行性疾病、炎症性疾病等的方法。
• N-Acylpolyamine inhibitors of HDM2 and HDMX binding to p53
  作者：Ryo Hayashi、Deyun Wang、Toshiaki Hara、Jaclyn A. Iera、Stewart R. Durell、Daniel H. Appella

  DOI：10.1016/j.bmc.2009.10.032

  日期：2009.12

  Selective inhibition of protein-protein interactions important for cellular processes could lead to the development of new therapies against disease. In the area of cancer, overexpression of the proteins human double minute 2 (HDM2) and its homolog HDMX has been linked to tumor aggressiveness. Both HDM2 and HDMX bind to p53 and prevent cell cycle arrest or apoptosis in damaged cells. Developing a strategy to simultaneously prevent the binding of both HDM2 and HDMX to p53 is an essential feature of inhibitors to restore p53 activity in a number of different cancers. Inhibition of protein-protein interactions with synthetic molecules is an emerging area of research that requires new inhibitors tailored to mimic the types of interfaces between proteins. Our strategy to create inhibitors of protein-protein interactions is to develop a non-natural scaffold that may be used as a starting point to identify important molecular components necessary for inhibition. In this study, we report an N-acylpolyamine (NAPA) scaffold that supports numerous sidechains in a compact atomic arrangement. NAPAs were constructed by a series of reductive aminations between amino acid derivatives followed by acylation at the resulting secondary amine. An optimized NAPA was able to equally inhibit the association of both HDM2 and HDMX with p53. Our results demonstrate some of the challenges associated with targeting multiple protein-protein interactions involved in overlapping cellular processes. Published by Elsevier Ltd.