9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine
• 英文别名: 9-(2-Hydroxyethylamino)-4-methyl-1-nitroacridine；2-[(4-methyl-1-nitroacridin-9-yl)amino]ethanol
• 化学式: C₁₆H₁₅N₃O₃
• 分子量: 297.313
• InChiKey: HTYYUAULNMXRJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine 在 氯化亚砜 、 丙酸 作用下， 以68%的产率得到9-(2-propionoxyethylamino)-4-methyl-1-nitroacridine
  参考文献：
  名称：

  9-alkylamino-1-nitroacridine derivatives

  摘要：

  这项发明涉及新型的9-羟基烷基氨基、9-烷氧基烷基氨基-1-硝基蒽衍生物。该发明还涵盖了制备方法、包含这些衍生物的药物组合物以及它们的医药用途。

  公开号：

  US06589961B2

文献信息

• [EN] THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR<br/>[FR] COMBINAISONS THÉRAPEUTIQUES D'UN INHIBITEUR DE LA BTK, D'UN INHIBITEUR DE LA PI3K, D'UN INHIBITEUR DE LA JAK-2 ET/OU D'UN INHIBITEUR DE LA CDK 4/6
  申请人：ACERTA PHARMA BV

  公开号：WO2016024232A1

  公开（公告）日：2016-02-18

  Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase- 4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.

  描述了磷脂酰肌醇3-激酶（PI3K）抑制剂的治疗组合，包括选择性作用于γ-和δ-异构体以及同时选择γ-和δ-异构体（PI3K-γ,δ, PI3K-γ和PI3K-δ）的PI3K抑制剂，一种Janus激酶-2（JAK-2）抑制剂，一种细胞周期依赖性激酶-4/6（CDK4/6）抑制剂，和/或一种Bruton氏酪氨酸激酶（BTK）抑制剂。在某些实施例中，该发明包括细胞周期依赖性激酶-4/6（CDK4/6）抑制剂和BTK抑制剂的治疗组合，PI3K-δ抑制剂和BTK抑制剂，JAK-2和BTK抑制剂，以及JAK-2、PI3K-δ和BTK抑制剂的治疗组合。
• 1-Nitroacridine/tumor inhibitor compositions
  申请人：——

  公开号：US20020037831A1

  公开（公告）日：2002-03-28

  The invention is directed to 1-nitroacridine derivative(s)/tumor inhibitor(s) compositions as well as methods for using said compositions for inhibiting or preventing tumor growth, particularly, prostate cancer cell growth and metastases.

  该发明涉及1-硝基吖啶衍生物/肿瘤抑制剂组合物，以及使用该组合物抑制或预防肿瘤生长的方法，特别是前列腺癌细胞生长和转移。
• 1-nitroacridine/tumor inhibitor compositions
  申请人：——

  公开号：US07622478B2

  公开（公告）日：2009-11-24

  The invention is directed to 1-nitroacridine derivative(s)/tumor inhibitor(s) compositions as well as methods for using said compositions for inhibiting or preventing tumor growth, particularly, prostate cancer cell growth and metastases.

  这项发明涉及1-硝基蒽衍生物/肿瘤抑制剂组合物，以及使用该组合物抑制或预防肿瘤生长的方法，特别是前列腺癌细胞生长和转移。
• Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
  作者：Iwona Gabriel、Kamila Rząd、Ewa Paluszkiewicz、Katarzyna Kozłowska-Tylingo

  DOI：10.3390/pathogens10020189

  日期：——

  In the last few years, increasing importance is attached to problems caused by fungal pathogens. Current methods of preventing fungal infections remain unsatisfactory. There are several antifungal compounds which are highly effective in some cases, however, they have limitations in usage: Nephrotoxicity and other adverse effects. In addition, the frequent use of available fungistatic drugs promotes drug resistance. Therefore, there is an urgent need for the development of a novel antifungal drug with a different mechanism of action, blocking of the fungal DNA topoisomerases activity appear to be a promising idea. According to previous studies on the m-AMSA moderate inhibitory effect on fungal topoisomerase II, we have decided to study Capridine β (also acridine derivative) antifungal activity, as well as its inhibitory potential on yeast topoisomerase II (yTOPOII). Results indicated that Capridine β antifungal activity depends on the kind of strains analyzed (MICs range 0.5–64 μg mL−1) and is related to its biotransformation in the cells. An investigation of metabolite formation, identified as Capridine β reduction product (IE1) by the fungus Candida albicans was performed. IE1 exhibited no activity against fungal cells due to an inability to enter the cells. Although no antifungal activity was observed, in contrast to Capridine β, biotransformation metabolite totally inhibited the yTOPOII-mediated relaxation at concentrations lower than detected for m-AMSA. The closely related Capridine β only slightly diminished the catalytic activity of yTOPOII.

  近年来，真菌病原体引起的问题越来越受到重视。目前预防真菌感染的方法仍不尽人意。有几种抗真菌化合物在某些情况下非常有效，但它们在使用上也有局限性：肾毒性和其他不良反应。此外，频繁使用现有的抗真菌药物会产生耐药性。因此，迫切需要开发一种作用机制不同的新型抗真菌药物，阻断真菌 DNA 拓扑异构酶的活性似乎是一个很有前景的想法。根据之前关于 m-AMSA 对真菌拓扑异构酶 II 有温和抑制作用的研究，我们决定研究 Capridine β（也是吖啶衍生物）的抗真菌活性及其对酵母拓扑异构酶 II（yTOPOII）的抑制潜力。结果表明，茵陈吖啶 β 的抗真菌活性取决于所分析的菌株种类（MICs 范围为 0.5-64 μg mL-1），并与其在细胞中的生物转化有关。研究人员对真菌白色念珠菌形成的代谢物进行了调查，确定其为 Capridine β 还原产物（IE1）。由于无法进入细胞，IE1 对真菌细胞没有活性。虽然没有观察到抗真菌活性，但与 Capridine β 相反，生物转化代谢物完全抑制了 yTOPOII 介导的松弛，其浓度低于 m-AMSA 的检测浓度。与之密切相关的 Capridine β 只略微降低了 yTOPOII 的催化活性。
• 9-ALKYLAMINO-1-NITROACRIDINE DERIVATIVES
  申请人：NEW YORK MEDICAL COLLEGE

  公开号：EP1257538B1

  公开（公告）日：2010-09-08