(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 | 117120-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (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
• 英文名称: carmethizole
• 英文别名: [1-methyl-5-(methylcarbamoyloxymethyl)-2-methylsulfanylimidazol-4-yl]methyl N-methylcarbamate
• CAS: 117120-88-4
• 化学式: C₁₁H₁₈N₄O₄S
• 分子量: 302.354
• InChiKey: BGYXTIDVSRHUEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (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 在 水 作用下， 生成 [5-(hydroxymethyl)-1-methyl-2-methylsulfanylimidazol-4-yl]methyl N-methylcarbamate
  参考文献：
  名称：

  Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole

  摘要：

  A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported.

  DOI：

  10.1021/jm00121a023
• 作为产物：
  描述：

  diethyl 2-(methylthio)imidazole-4,5-dicarboxylate 在 lithium aluminium tetrahydride 、 dibutyltin diacetate 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 19.0h， 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：

  Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole

  摘要：

  A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported.

  DOI：

  10.1021/jm00121a023

文献信息

• SYNTHESIS OF 4H-BENZO[D]PYRROLO[1,2-A]THIAZOLES AND INDOLIZINO[6,7-b]INDOLE DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS
  申请人：Su Tsann-Long

  公开号：US20130178629A1

  公开（公告）日：2013-07-11

  The present invention provides a series of 2,3-bis(hydroxymethyl)-4H-benzo[d]pyrrolo-[1,2-a]thiazoles and 1,2-bis(hydroxymethyl)indolizino[6,7-b]indole derivatives and their bis(alkylcarbamates) derivatives. These derivatives were designed as bi-functional DNA cross-linking agents. The in vitro cytotoxicity study of these compounds revealed that they exhibit significant anti-proliferative activity in inhibiting human lymphoblastic leukemia and various solid tumor cell growth. The compounds also exhibit therapeutic efficacy against human breast carcinoma and lung cancer in xenograft model. The compounds generally possess potent antitumor activity to kill various human solid tumors and have high potential for clinical applications.

  本发明提供了一系列2,3-双(羟甲基)-4H-苯并[d]吡咯-[1,2-a]噻唑和1,2-双(羟甲基)吲哚并[6,7-b]吲哚衍生物及其双(烷基氨基甲酸酯)衍生物。这些衍生物被设计为具有双功能DNA交联作用的剂。对这些化合物进行的体外细胞毒性研究表明，它们在抑制人淋巴母细胞白血病和各种实体肿瘤细胞生长方面表现出显著的抗增殖活性。这些化合物还在异种移植模型中对人类乳腺癌和肺癌表现出治疗效果。这些化合物通常具有强大的抗肿瘤活性，可以杀死各种人类实体肿瘤，并具有高潜力用于临床应用。
• Synthesis, chemical reactivity, and antitumor evaluation of congeners of carmethizole hydrochloride, an experimental acylated vinylogous carbinolamine tumor inhibitor
  作者：Mark A. Jarosinski、Peech S. Reddy、Wayne K. Anderson

  DOI：10.1021/jm00075a017

  日期：1993.11

  A series of analogues of 4,5-bis(((N-methylcarbamoyl)oxy)methyl)-1-methyl-2-(methylthio)-imidazole (1, carmethizole) were synthesized. The chemical reactivities of the analogues (as electrophiles) were evaluated and related to the antitumor activity (in vivo and in vitro). Changes in the alkylthio moiety had a significant effect upon the chemical reactivity. Electron-withdrawing groups on the sulfur decreased chemical reactivity and, in parallel, decreased antitumor activity. Carmethizole sulfoxide (11a) was unreactive as an electrophile and exhibited no antitumor activity either in vivo or in vitro; this led to the conclusion that carmethizole sulfoxide was not acting as a ''carrier form'' of carmethizole, The disulfides 17 and 18 were unreactive as electrophiles but did exhibit antitumor activity. The activity of 17 and 18 was attributed to the thiol 10 that would be generated upon cleavage of the disulfide bond.
• A new synthesis of carmethizole and related nitrogen analogues
  作者：Michael P. Hay、William A. Denny

  DOI：10.1016/s0040-4039(97)10238-6

  日期：1997.12

  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.
• ANDERSON, W. K.;BHATTACHARJEE, D.;HOUSTON, D. M., J. MED. CHEM., 32,(1989) N, C. 119-127
  作者：ANDERSON, W. K.、BHATTACHARJEE, D.、HOUSTON, D. M.

  DOI：——

  日期：——
• Bis (acyloxymethyl) imidazole Derivative
  申请人：THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK

  公开号：EP0313724B1

  公开（公告）日：1995-08-09