4-(氯甲基)-1H-咪唑-1-羧酸叔丁酯 | 500782-71-8

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(氯甲基)-1H-咪唑-1-羧酸叔丁酯
• 英文名称: 4-(chloromethyl)imidazole-1-carboxylic acid tert-butyl ester
• 英文别名: 1-t-butoxycarbonyl-4-chloromethylimidazole；1,1-dimethylethyl 4-(chloromethyl)-1H-imidazole-1-carboxylate；Tert-butyl 4-(chloromethyl)-1H-imidazole-1-carboxylate；tert-butyl 4-(chloromethyl)imidazole-1-carboxylate
• CAS: 500782-71-8
• 化学式: C₉H₁₃ClN₂O₂
• 分子量: 216.667
• InChiKey: WEVUSNXEJVVWOD-UHFFFAOYSA-N

物化性质

• 沸点：
  319.1±34.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  4-(氯甲基)-1H-咪唑-1-羧酸叔丁酯 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.5h， 生成 4-{1-[(1-methoxycarbonyl-3-methylsulfanylpropylcarbamoyl)methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl}-imidazole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent and selective benzoyleneurea-based inhibitors of protein geranylgeranyltransferase-I

  摘要：

  A series of novel protein geranylgeranyltransferase-I (PGGTase-I) inhibitors based on a benzoyleneurea scaffold has been synthesized. Using a benzoyleneurea scaffold as a mimetic for the central dipeptide (AA), we have developed CAAX peptidomimetic inhibitors that selectively block the activity of PGGTase-I over the closely related enzyme protein farnesyltransferase. In this new class of PGGTase-I inhibitors, compound (6c) with X = L-phenylalanine displayed the highest inhibition activity against PGGTase-I with an IC50 value of 170 nM. The inhibitors described in this study represent novel and promising leads for the development of potent and selective inhibitors of mammalian PGGTase-I for potential application as antitumor agents. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.053
• 作为产物：
  描述：

  4-(羟基甲基)-1H-咪唑-1-羧酸叔丁酯 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以58%的产率得到4-(氯甲基)-1H-咪唑-1-羧酸叔丁酯
  参考文献：
  名称：

  发现 2-亚磺酰基-二氮杂双环辛烷衍生物，潜在的口服 β-内酰胺酶抑制剂，用于由产丝氨酸 β-内酰胺酶的肠杆菌引起的感染

  摘要：

  β-内酰胺和β-内酰胺酶抑制剂（BLI）的共同给药是治疗β-内酰胺耐药革兰氏阴性菌引起的细菌感染的成熟治疗措施之一，而对于口服活性BLI，克拉维酸只有两种选择和舒巴坦。此外，由于新的 β-内酰胺酶（包括属于 A 类 β-内酰胺酶、C 类和 D 类 β-内酰胺酶以及碳青霉烯酶的超广谱 β-内酰胺酶 (ESBL)）的传播，这些 BLI 正在失去其临床用途。这些经典 BLI 几乎或不受抑制。从医疗费用和医护人员负担的角度来看，口服疗法具有许多优势。在我们寻找在 C2 位具有硫基官能团的新型二氮杂双环辛烷 (DBO) BLI 时，我们发现了一种 2-亚磺酰基-DBO 衍生物（2 )，它恢复了口服可用的第三代头孢菌素头孢布坦 (CTB) 对各种丝氨酸 β-内酰胺酶产生菌株的抗菌活性，包括耐碳青霉烯的肠杆菌科 (CRE)。它可以通过酯前药修饰口服吸收，并在与 CTB 组合时表现出体内功效。

  DOI：

  10.1021/acs.jmedchem.1c00799

文献信息

• [EN] TRIAZOLOPYRIDINE AND TRIAZOLOPYRIMIDINE INHIBITORS OF MYELOPEROXIDASE<br/>[FR] INHIBITEURS DE MYÉLOPEROXYDASE DE TYPE TRIAZOLOPYRIDINE ET TRIAZOLOPYRIMIDINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016040417A1

  公开（公告）日：2016-03-17

  The present invention provides compounds of Formula (I): wherein A and R1 are each as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

  本发明提供了式（I）的化合物：其中A和R1如规范中所定义，并包括任何此类新化合物的组合物。这些化合物是髓过氧化物酶（MPO）抑制剂和/或嗜酸性粒细胞过氧化物酶（EPX）抑制剂，可用作药物。
• Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I
  作者：Hairuo Peng、Dora Carrico、Van Thai、Michelle Blaskovich、Cynthia Bucher、Erin E. Pusateri、Said M. Sebti、Andrew D. Hamilton

  DOI：10.1039/b517572k

  日期：——

  A series of compounds based on the carboxyl-terminal CAAL sequence of PGGTase-I substrates was designed and synthesized. Using piperazin-2-one as a semi-rigid scaffold, we have introduced critical pharmacophores in a well-defined arrangement to mimic the CAAL sequence. High potency and exceptional selectivity were obtained for inhibition of PGGTase-I with structures such as 45 and 70. Potency of this series of GGTIs was dependent on the presence of an L-leucine residue with a free carboxyl terminus, as well as an S configuration of the 3-aryl group. The selectivity was significantly enhanced by 5-methyl substitution on the imidazole ring and fluorine substitution on the 3-aryl group. Modification of the 6-position of the piperazinone scaffold was found to be unfavorable. Compounds 44 and 69, the corresponding methyl esters of 45 and 70, were found to selectively block processing of Rap1A by PGGTase-I in whole cells with IC50 values of 0.4 µM and 0.7 µM respectively.

  基于PGGTase-I底物的羧端CAAL序列，设计并合成了一系列化合物。我们利用哌嗪-2-酮作为半刚性骨架，在明确有序的排列中引入了关键的药效团，以模拟CAAL序列。对于抑制PGGTase-I，如45和70结构所展现，其活性高且选择性极佳。这一系列GGTIs的活性依赖于具有自由羧端的L-亮氨酸残基以及3-芳基的S构型。通过咪唑环上的5-甲基取代和3-芳基上的氟取代，其选择性显著提升。发现对哌嗪酮骨架的6位进行修饰是不利的。化合物44和69，即45和70的相应甲酯，分别以0.4 µM和0.7 µM的IC50值选择性地阻断PGGTase-I对Rap1A的细胞内加工。
• Chemical Compounds
  申请人：Turnbull Philip Stewart

  公开号：US20090170907A1

  公开（公告）日：2009-07-02

  This invention relates to non-steroidal compounds that are modulators of androgen, glucocorticoid, mineralocorticoid, and progesterone receptors, and also to the methods for the making and use of such compounds.

  这项发明涉及非甾体化合物，它们是雄激素、糖皮质激素、矿质皮质激素和孕激素受体的调节剂，以及这些化合物的制备和使用方法。
• Structure-based design of imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase
  作者：Junko Ohkanda、Corey L. Strickland、Michelle A. Blaskovich、Dora Carrico、Jeffrey W. Lockman、Andreas Vogt、Cynthia J. Bucher、Jiazhi Sun、Yimin Qian、David Knowles、Erin E. Pusateri、Saïd M. Sebti、Andrew D. Hamilton

  DOI：10.1039/b508184j

  日期：——

  A series of imidazole-containing peptidomimetic PFTase inhibitors and their co-crystal structures bound to PFTase and FPP are reported. The structures reveal that the peptidomimetics adopt a similar conformation to that of the extended CVIM tetrapeptide, with the imidazole group coordinating to the catalytic zinc ion. Both mono- and bis-imidazole-containing derivatives, 13 and 16, showed remarkably high enzyme inhibition activity against PFTase in vitro with IC50 values of 0.86 and 1.7 nM, respectively. The peptidomimetics were also highly selective for PFTase over PGGTase-I both in vitro and in intact cells. In addition, peptidomimetics 13 and 16 were found to suppress tumor growth in nude mouse xenograft models with no gross toxicity at a daily dose of 25 mg kg−1.

  报道了一系列含有咪唑基的肽模拟物PFTase抑制剂及其与PFTase和FPP结合的共晶结构。这些结构揭示了肽模拟物采取类似于延伸的CVIM四肽的构象，其中的咪唑基团与催化锌离子配位。含有单咪唑和双咪唑的衍生物13和16，在体外分别表现出对PFTase极高的酶抑制活性，IC50值分别为0.86和1.7 nM。这些肽模拟物对PFTase的选择性优于PGGTase-I，无论是在体外还是在完整的细胞中。此外，肽模拟物13和16在裸鼠异种移植模型中能抑制肿瘤生长，以每天25 mg kg−1的剂量给药时没有明显的毒性。
• Piperazinone compounds as anti-tumor and anti-cancer agents and methods of treatment
  申请人：Yale University

  公开号：EP2014291A2

  公开（公告）日：2009-01-14

  The present invention relates to piperazinone compounds, pharmaceutical compositions containing those compounds and methods of treating tumors and cancer, among other disease states and conditions in mammalian patients, especially including humans.

  本发明涉及哌嗪酮化合物、含有这些化合物的药物组合物以及治疗哺乳动物患者（尤其包括人类）肿瘤和癌症等疾病状态和病症的方法。