5-(异氰酸甲基)-1,3-苯并二氧戊环 | 71217-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: 5-(异氰酸甲基)-1,3-苯并二氧戊环
• 中文别名: 5-(异氰酸基甲基)-1,2-亚甲二氧基苯
• 英文名称: 5-(isocyanatomethyl)-2H-1,3-benzodioxole
• 英文别名: 5-(isocyanatomethyl)-1,3-benzodioxole
• CAS: 71217-46-4
• 化学式: C₉H₇NO₃
• 分子量: 177.159
• InChiKey: RIUNOJGBBOBVDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(异氰酸甲基)-1,3-苯并二氧戊环 在 1,2-二甲基咪唑 作用下， 以 二氯甲烷 为溶剂， 生成 1,3-Bis-benzo[1,3]dioxol-4-ylmethyl-[1,3]diazetidine-2,4-dione
  参考文献：
  名称：

  Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones

  摘要：

  The present work demonstrates that the 1,3-diazetidifie-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and alpha -chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00264-5
• 作为产物：
  描述：

  胡椒乙酸 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 生成 5-(异氰酸甲基)-1,3-苯并二氧戊环
  参考文献：
  名称：

  Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones

  摘要：

  The present work demonstrates that the 1,3-diazetidifie-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and alpha -chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00264-5

文献信息

• [EN] COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES<br/>[FR] COMPOSÉS, SELS CORRESPONDANTS ET MÉTHODES POUR LE TRAITEMENT DE MALADIES
  申请人：ACADIA PHARM INC

  公开号：WO2019040107A1

  公开（公告）日：2019-02-28

  The present disclosure relates to compounds according to Formula (I), useful for treating diseases.

  本公开涉及按照式（I）的化合物，用于治疗疾病。
• Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity
  作者：Daria Giacomini、Giulia Martelli、Miriam Piccichè、Enrico Calaresu、Clementina Elvezia Cocuzza、Rosario Musumeci

  DOI：10.1002/cmdc.201700307

  日期：2017.9.21

  4‐alkylidene‐β‐lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl‐carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl‐carbamate β‐lactams were shown to be valuable antibacterial agents against selected linezolid‐resistant

  在诸如囊性纤维化（CF）的慢性病理中，多重耐药细菌菌株的出现特别重要，在这种情况下，频繁重复使用抗菌剂有利于持久定植和选择耐药菌株。金黄色葡萄球菌是CF患者的常见病原体，与多药耐药性相关。在以前的研究中，我们证明了与β-内酰胺直接连接的4亚烷基侧链的出现似乎增强了对金黄色葡萄球菌的效力，尤其是对耐甲氧西林的金黄色葡萄球菌的效力。（MRSA）菌株。在本研究中，合成了21种新的4-亚烷基-β-内酰胺，并对其抗菌活性进行了评估。我们设计的新化合物在C3羟乙基侧链上具有芳基，苄基或苯乙基氨基甲酸酯基团。我们发现有生物活性和氨基甲酸酯基团的氮取代基，和两个苯乙基-氨基甲酸叔丁酯β内酰胺之间的相关性被证明是针对选定的耐利奈唑胺菌株有价值的抗菌剂，具有2-4毫克的L的最小抑菌浓度- 1。
• Assessment of the structure-activity relationship and antileukemic activity of diacylpyramide compounds as human ClpP agonists
  作者：Ranran Zhang、Pengyu Wang、Bingyan Wei、Liang Chen、Xiaomin Song、Yihui Pan、Jiahui Li、Jianhua Gan、Tao Zhang、Cai-Guang Yang

  DOI：10.1016/j.ejmech.2023.115577

  日期：2023.10

  (ClpP) is required for the regulatory hydrolysis of mitochondrial proteins. Allosteric ClpP agonists dysfunctionally activate mitochondrial ClpP in antileukemic therapies. We previously developed ZG111, a potent ClpP agonist derived from ICG-001, inhibits the proliferation of pancreatic ductal adenocarcinoma cell lines in vitro and in vivo by degrading respiratory chain complex proteins. Herein, we studied

  线粒体蛋白的调节性水解需要人酪蛋白分解酶 P (ClpP) 。在抗白血病治疗中，变构 ClpP 激动剂会功能失调地激活线粒体 ClpP 。我们之前开发了ZG111 ，一种源自ICG-001的有效 ClpP 激动剂，通过降解呼吸链复合蛋白在体外和体内抑制胰腺导管腺癌细胞系的增殖。在此，我们研究了ICG-001类似物作为抗白血病药物的构效关系。与ZG111的稳定作用相比，化合物ZG36对急性髓系白血病（AML）细胞系中ClpP的热稳定性表现出改善的稳定作用，表明ZG36和ClpP之间的直接结合。事实上，解析的ZG36 /ClpP 结构复合物揭示了ZG36在 ClpP 结合过程中的作用模式。化合物ZG36非选择性降解呼吸链复合物并减少线粒体 DNA，最终导致线粒体功能崩溃和白血病细胞死亡。最后， ZG36治疗可抑制体外3-D 细胞生长，并抑制异种移植小鼠模型中 AML 细胞的肿瘤发生。 总的来说，我们开发了一种新型人类
• Compounds, salts thereof and methods for treatment of diseases
  申请人：ACADIA PHARMACEUTICALS INC.

  公开号：US11345693B2

  公开（公告）日：2022-05-31

  The present disclosure relates to compounds according to Formula (I), useful for treating diseases.

  本公开涉及可用于治疗疾病的式 (I) 化合物。
• Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones
  作者：Shrenik K. Shah、Conrad P. Dorn、Paul E. Finke、Jeffrey J. Hale、William K. Hagmann、Karen A. Brause、Gilbert O. Chandler、Amy L. Kissinger、Bonnie M. Ashe

  DOI：10.1021/jm00099a003

  日期：1992.10

  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.