1,1-dimethylethyl N-(4-(isothiocyanatomethyl)phenylmethyl)carbamate | 184954-76-5

• 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: 1,1-dimethylethyl N-(4-(isothiocyanatomethyl)phenylmethyl)carbamate
• 英文别名: 4-(tert-butoxycarbonylaminomethyl)benzyl isothiocyanate；tert-butyl (4-(isothiocyanatomethyl)benzyl)carbamate；tert-butyl N-[[4-(isothiocyanatomethyl)phenyl]methyl]carbamate
• CAS: 184954-76-5
• 化学式: C₁₄H₁₈N₂O₂S
• 分子量: 278.375
• InChiKey: WYRHEVHZURQOQV-UHFFFAOYSA-N

物化性质

• 熔点：
  80-82 °C
• 沸点：
  431.1±33.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl N-(4-(isothiocyanatomethyl)phenylmethyl)carbamate 在 磺酰氯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 4-(4-(aminomethyl)benzyl)-2-(4-methoxyphenyl)-1,2,4-thiadiazolidine-3,5-dione
  参考文献：
  名称：

  [EN] NOVEL TDZD ANALOGS AS AGENTS THAT DELAY, PREVENT, OR REVERSE AGE-ASSOCIATED DISEASES; AND AS ANTI-CANCER AND ANTILEUKEMIC AGENTS
  [FR] NOUVEAUX ANALOGUES DE TDZD EN TANT QU'AGENTS QUI RETARDENT, PRÉVIENNENT OU INVERSENT DES MALADIES ASSOCIÉES À L'ÂGE; ET EN TANT QU'AGENTS ANTICANCÉREUX ET ANTILEUCÉMIQUES

  摘要：

  本公开涉及用于治疗各种神经退行性疾病，例如肌肉减少症、核上性瘫痪、阿尔茨海默病、帕金森病、亨廷顿病和痴呆，以及各种癌症，例如肉瘤、癌、血液肿瘤、实体肿瘤、乳腺癌、宫颈癌、胃肠癌、结直肠癌、脑癌、皮肤癌、前列腺癌、卵巢癌、膀胱癌、甲状腺癌、睾丸癌、胰腺癌、子宫内膜癌、黑色素瘤、神经胶质瘤、白血病、淋巴瘤、慢性骨髓增殖性疾病、骨髓增生异常综合征、骨髓增殖性肿瘤和浆细胞肿瘤（骨髓瘤）的TDZD类似物。本摘要旨在作为在特定技术领域内进行搜索的扫描工具，并不是用来限制本发明的。

  公开号：

  WO2021163572A1
• 作为产物：
  描述：

  1,4-苯二甲胺 在 三乙胺 、 calcium carbonate 作用下， 以 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 32.0h， 生成 1,1-dimethylethyl N-(4-(isothiocyanatomethyl)phenylmethyl)carbamate
  参考文献：
  名称：

  Synthesis of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas and evaluation as modulators of the isoforms of nitric oxide synthase

  摘要：

  Inhibition of the isoforms of nitric oxide synthase (NOS) has important applications in therapy of several diseases, including cancer. Using 1400W [N-(3-aminomethylbenzyl)acetamidme], thiocitrulline and N-delta-(4,5-dihydrothiazol-2-yl)ornithine as lead compounds, series of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas were designed as inhibitors of NOS. Ring-substituted benzyl and phenyl isothiocyanates were synthesised by condensation of the corresponding amines with thiophosgene and addition of ammonia gave the corresponding thioureas in high yields. The substituted 2-amino-4,5-dihydrothiazoles were approached by two routes. Treatment of simple benzylamines with 2-methylthio-4,5-dihydrothiazole at 180degreesC afforded the corresponding 2-benzylamino-4,5-dihydrothiazoles. For less nucleophilic amines and those carrying more thermally labile substituents, the 4,5-dihydrothiazoles were approached by acid-catalysed cyclisation of N-(2-hydroxyethyl)thioureas. This cyclisation was shown to proceed by an S(N)2-like process. Modest inhibitory activity was shown by most of the thioureas and 4,5-dihydrothiazoles, with N-(3-aminomethylphenyl)thiourea (IC50 = 13 muM vs rat neuronal NOS and IC50 = 23 muM vs rat inducible NOS) and 2-(3-aminomethylphenylamino)-4,5-dihydrothiazole (IC50 - 13 muM vs rat neuronal NOS and IC50 = 19 muM vs human inducible NOS) being the most potent. Several thioureas and 4,5-dihydrothiazoles were found to stimulate the activity of human inducible NOS in a time-dependent manner. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00451-6

文献信息

• Symmetry Complementarity-Guided Design of Anthrax Toxin Inhibitors Based on β-Cyclodextrin: Synthesis and Relative Activities of Face-Selective Functionalized Polycationic Clusters
  作者：Alejandro Díaz-Moscoso、Alejandro Méndez-Ardoy、Fernando Ortega-Caballero、Juan M. Benito、Carmen Ortiz Mellet、Jacques Defaye、Tanisha M. Robinson、Adiamseged Yohannes、Vladimir A. Karginov、José M. García Fernández

  DOI：10.1002/cmdc.201000419

  日期：2011.1.3

  potential anthrax toxin inhibitors based on the β‐cyclodextrin (βCD) scaffold were developed by exploiting face‐selective CuI‐catalyzed azide–alkyne 1,3‐cycloadditions, amine–isothiocyanate coupling, and allyl group hydroboration–oxidation/hydroxy → amine replacement reactions. The molecular design follows the “symmetry–complementarity” concept between homogeneously functionalized polycationic βCD derivatives

  通过利用面选择性Cu I催化的叠氮化物-炔烃1,3-环加成反应，胺-异硫氰酸酯偶联以及烯丙基氢硼化-氧化/开发了三种基于β-环糊精（βCD）支架的潜在炭疽毒素抑制剂新系列。羟基→胺替代反应。分子设计遵循均相官能化的聚阳离子βCD衍生物与保护性抗原（PA）之间的“对称性-互补性”概念，PA是已知形成C 7的炭疽毒素的一种成分致死和浮肿因子利用细胞膜上的对称孔获得细胞溶质的通道。本文报道了一系列阳离子分子的数量，排列和表面位置不同的βCD衍生物的合成和抗毒素活性。这些结果为新候选人对抗炭疽威胁的结构-活动关系发展计划奠定了基础。
• Polycationic Amphiphilic Cyclodextrins for Gene Delivery: Synthesis and Effect of Structural Modifications on Plasmid DNA Complex Stability, Cytotoxicity, and Gene Expression
  作者：Alejandro Díaz-Moscoso、Löic Le Gourriérec、Marta Gómez-García、Juan M. Benito、Patricia Balbuena、Fernando Ortega-Caballero、Nicolas Guilloteau、Christophe Di Giorgio、Pierre Vierling、Jacques Defaye、Carmen Ortiz Mellet、José M. García Fernández

  DOI：10.1002/chem.200901149

  日期：2009.11.23

  be intimately dependent on architectural features. Facial amphiphilicity and the presence of a cluster of cationic and hydrogen‐bonding centers for cooperative and reversible complexation of the polyanionic DNA chain is crucial to attain high transgene expression levels with very low toxicity profiles. Further enhancement of gene expression, eventually overcoming that of polyplexes from commercial

  报道了一种以分子多样性为导向的方法，用于制备定义明确的聚阳离子两亲环糊精（paCD）作为基因传递系统。合成策略利用CD圆环上伯羟基和仲羟基的不同反应性，分别用阳离子元素和亲脂性尾区区域选择性地修饰每个边缘。电荷密度和疏水-亲水平衡都可以在高度对称的结构中进行微调，这使人联想到两种最突出的非病毒基因载体阳离子脂质和阳离子聚合物。paCD的单分散性质和合成方案的模块性特别适合于结构-活性关系研究。凝胶电泳显示，在存在质粒DNA（pDNA）的情况下，paCD能够自组装，从而提供70-150 nm的均匀，稳定的纳米颗粒（CDplex），可以完全保护pDNA免受环境污染。在没有血清和存在血清的情况下，已在BNL-CL2和COS-7细胞系上体外研究了所得CDplex的转染效率，发现其与体系结构特征密切相关。面部两亲性以及聚阴离子DNA链协同和可逆络合的阳离子和氢键中心簇的存在对于获得高转基因表达水平和
• CRBN免疫调节剂
  申请人：首药控股（北京）股份有限公司

  公开号：CN116023368A

  公开（公告）日：2023-04-28

  本申请涉及式I所示的CRBN免疫调节剂.具体地，本发明涉及CRBN免疫调节的小分子化合物、其制备方法、其药物组合物，还涉及这类化合物及其药物组合物在制备治疗与细胞增殖异常相关的疾病的药物中的用途，例如治疗癌症。
• Solid and Solution Phase Organic Syntheses of Oligomeric Thioureas
  作者：Joseph Smith、Jennifer L. Liras、Stephen E. Schneider、Eric V. Anslyn

  DOI：10.1021/jo9614102

  日期：1996.1.1

  In order to study supramolecular architectures built from unnatural oligomeric and polymeric structures, one must first have an efficient synthetic strategy to produce them. Oligomers built from thiourea groups should form complex secondary and tertiary structures due to the hydrogen-bonding capabilities of the thioureas. Herein, both solution and solid phase synthetic procedures that yield oligomeric thioureas are described. They rely on the coupling of an isothiocyanate with an amine to produce the thiourea linkage. The monomers are derived from simple diamines. Higher yields are achieved using the solid phase method due to the ability to easily monitor the extent of reaction, to use a large excess of reagent, and to perform purification after cleavage from the solid support. A variety of oligomers are given as examples. The procedure is quite general, should be easily extended to complex monomers, and will allow the investigation of intramolecular and intermolecular interactions.
• INHIBITORS OF DEUBIQUITINATING PROTEASES
  申请人：Brandeis University

  公开号：US20170204055A1

  公开（公告）日：2017-07-20

  Disclosed are small molecule inhibitors of deubiquitinating enzymes (DUBs), and methods of using them. Certain compounds are selective for particular ubiquitin-specific proteases (USPs).