4,5-bis(hydroxymethyl)-1-methyl-1H-imidazole | 33457-49-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4,5-bis(hydroxymethyl)-1-methyl-1H-imidazole
• 英文别名: (1-methyl-1H-imidazole-4,5-diyl)-bis-methanol；1H-Imidazole-4,5-dimethanol, 1-methyl-；[5-(hydroxymethyl)-1-methylimidazol-4-yl]methanol
• CAS: 33457-49-7
• 化学式: C₆H₁₀N₂O₂
• 分子量: 142.158
• InChiKey: JUIBTHOYWZDBEJ-UHFFFAOYSA-N

物化性质

• 沸点：
  419.8±35.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-bis(hydroxymethyl)-1-methyl-1H-imidazole 在 正丁基锂 、 四丁基氟化铵 、 二乙酸二丁基锡 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1-甲基-4-((((甲基氨基)羰基)氧基)甲基)-2-(甲硫基)-1H-咪唑-5-基)甲基甲基氨基甲酸酯盐酸盐
  参考文献：
  名称：

  A new synthesis of carmethizole and related nitrogen analogues

  摘要：

  A new efficient six-step synthesis of carmethizole, a novel bis-carbamate alkylating agent, and syntheses of related nitrogen analogues are described, using a key 4,5-disubstituted imidazole intermediate 8. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)10238-6
• 作为产物：
  描述：

  咪唑-4,5-二羧酸 在 lithium aluminium tetrahydride 、 氯化亚砜 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.0h， 生成 4,5-bis(hydroxymethyl)-1-methyl-1H-imidazole
  参考文献：
  名称：

  Design, Synthesis and Evaluation of Imidazolylmethyl Carbamate Prodrugs of Alkylating Agents

  摘要：

  Two approaches to prodrugs of alkylating agents based on an imidazolylmethyl carbamate nucleus were explored. A 2-azido analogue (3) of the bis-carbamate carmethizole (1) displayed similar aerobic cytotoxicity to 1 in a panel of human and murine cell lines. Approaches to the 2-amino and 2-carbamoyl analogues are described. In the second approach an imidazolylmethanol was used as a 'trigger' linked via a carbamate to the alkylating agent N,N-bis(2-chlorethyl)amine (BCEA). Nitroimidazole and methylsulphinylimidazole carbamate prodrugs 6-8 were 5-20-fold less toxic than BCEA. Despite this deactivation in the prodrug form, little increase in cytotoxicity was observed under hypoxia. The data suggest that BCEA released on bioreduction is not sufficiently potent to contribute significant additional cytotoxicity. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)01031-5

文献信息

• A tropylium annulated N-heterocyclic carbene
  作者：Sebastian Appel、Peter Brüggemann、Christian Ganter

  DOI：10.1039/d0cc04482b

  日期：——

  Derivatives of the cationic tropylium annulated imidazolylidene ITrop+ are obtained by hydride abstraction from related cycloheptatriene compounds. Spectroscopic, structural and theoretical data indicate that, as a cationic relative of benzimidazolylidenes, ITrop+ has highly reduced σ-donor and strong π-acceptor character.

  通过氢化物从相关的环庚三烯化合物中提取氢化物，可以得到阳离子对苯二甲酰基咪唑基亚烷基ITrop +的衍生物。光谱，结构和理论数据表明，ITrop +作为苯并咪唑基亚胺的阳离子亲和性，具有高度还原的σ供体和强的π受体特性。
• Propane-1,3-Dione Derivative or Salt Thereof
  申请人：Hirano Masaaki

  公开号：US20090181964A1

  公开（公告）日：2009-07-16

  It is intended to provide a compound useful as a GnRH receptor antagonist. The inventors further investigated propane-1,3-dione derivatives. As a result, they confirmed that a compound having a benzene ring or a thiophene ring substituted with a group represented by —SO 2 —R 3 in a propane-1,3-dione derivative having 2-(1,3-dihydro-2H-benzimidazol-2-ylidene) has an excellent GnRH receptor antagonistic effect and accomplished the present invention. Because the compound of the present invention has a potent GnRH receptor antagonistic effect, it is useful for the treatment of sex hormone-dependent diseases, particularly GnRH-related diseases. Further, because the compound of the present invention has an excellent metabolic stability in human and few drug interactions, therefore it has preferable characteristics as a pharmaceutical used for the above-mentioned diseases.

  本发明旨在提供一种作为GnRH受体拮抗剂有用的化合物。发明人进一步研究了丙酮酸1,3-二酮衍生物。结果，他们证实，在2-(1,3-二氢-2H-苯并咪唑-2-基亚胺)具有苯环或噻吩环的衍生物中，取代为—SO2—R3基团的化合物具有出色的GnRH受体拮抗作用，并完成了本发明。由于本发明的化合物具有强效的GnRH受体拮抗作用，因此对于治疗性激素依赖性疾病，特别是GnRH相关疾病非常有用。此外，由于本发明的化合物在人体内具有出色的代谢稳定性和较少的药物相互作用，因此作为用于上述疾病的药物具有良好的特性。
• PROPANE-1,3-DION DERIVATIVE OR SALT THEREOF
  申请人：Astellas Pharma Inc.

  公开号：EP1864976B1

  公开（公告）日：2012-10-10
• Ohba, Masashi; Mukaihira, Takafumi; Fuji, Tozo, Heterocycles, 1992, vol. 33, # 1, p. 21 - 26
  作者：Ohba, Masashi、Mukaihira, Takafumi、Fuji, Tozo

  DOI：——

  日期：——
• US7960562B2
  申请人：——

  公开号：US7960562B2

  公开（公告）日：2011-06-14