N-羟基-N’-(4-丁基-2-甲基苯基)甲脒 | 339068-25-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-羟基-N’-(4-丁基-2-甲基苯基)甲脒
• 英文名称: N-(4-butyl-2-methylphenyl)-N'-hydroxy-formamidine
• 英文别名: N'-(4-butyl-2-methylphenyl)-N-hydroxymethanimidamide
• CAS: 339068-25-6
• 化学式: C₁₂H₁₈N₂O
• 分子量: 206.288
• InChiKey: LYNOGBKNFIHKLE-UHFFFAOYSA-N

物化性质

• 熔点：
  138-140°C
• 溶解度：
  可溶于氯仿（少许）、乙醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.6
• 氢给体数：
  2
• 氢受体数：
  2

制备方法与用途

用途

HET-0016 是一种高效且选择性的20-HETE 生物合成抑制剂，通过抑制CYP4A（人类 IC50=8.9 nM，大鼠肾微粒体35 nM）起作用。其对其他CYP同工酶的IC50分别为：CYP2C9-3.3 uM、CYP2D6-83.9 uM、CYP3A4-71 uM。该化合物能抑制由钙离子或花生四烯酸引起的脑血管收缩，并在多种模型中抑制血管生成和内皮细胞分支。此外，HET-0016 在临时局部缺血后的大脑损伤保护方面显示出保护作用（剂量为10 mg/Kg）。

用途 生物试剂

反应信息

• 作为产物：
  描述：

  4-丁基-2-甲基苯胺 在 盐酸羟胺 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 N-羟基-N’-(4-丁基-2-甲基苯基)甲脒
  参考文献：
  名称：

  Discovery of a N′-hydroxyphenylformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor

  摘要：

  N-(4-Butyl-2-methylphenyl)-N'-hydroxyformamidine (HET0016) was evaluated as the first potent and selective inhibitor of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) synthase. The IC50 value of HET0016 for the production of 20-HETE from arachidonic acid (AA) by human renal microsomes was 8.9 +/- 2.7 nM, with over 200 times the selectivity of xenobiotic-metabolizing cytochrome P450 enzymes. An examination of the structure-activity relationship revealed that the unsubstituted hydroxyformamidine moiety and the substituent at the para-position of the N-hydroxyformamidine moiety are necessary for the potent activity of HET0016. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00614-x

文献信息

• USE OF CYP EXPRESSION TO DIRECT THERAPEUTIC INTERVENTION IN CANCER
  申请人：REGENTS OF THE UNIVERSITY OF MINNESOTA

  公开号：US20180177749A1

  公开（公告）日：2018-06-28

  Certain embodiments of the invention provide a method for identifying a cancer cell that is sensitive to a biguanide compound or other CYP epoxygenase inhibitor, comprising detecting increased expression of at least one cytochrome P450 (CYP) and/or decreased expression of soluble epoxide hydrolase (EPHX2) in the cancer cell, wherein increased CYP expression and/or decreased expression of EPHX2 in the cancer cell correlates with increased sensitivity of the cancer cell to the biguanide compound or other CYP epoxygenase inhibitor.

  本发明的某些实施例提供了一种用于识别对双胍类化合物或其他CYP环氧化酶抑制剂敏感的癌细胞的方法，包括检测癌细胞中至少一个细胞色素P450（CYP）的表达增加和/或可溶性环氧化物水解酶（EPHX2）的表达减少，其中癌细胞中CYP表达增加和/或EPHX2表达减少与癌细胞对双胍类化合物或其他CYP环氧化酶抑制剂的敏感性增加相关。
• THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS
  申请人：BROWN Dennis M.

  公开号：US20160045502A1

  公开（公告）日：2016-02-18

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

  本发明描述了一种改善先前受到治疗性能不佳限制的治疗剂的治疗效果的方法和组合物，通过改善单药疗法的功效或减少副作用。这种方法和组合物特别适用于芥子碱基烷基化剂，例如尿嘧啶芥和其类似物、衍生物或前药，包括6-甲基尿嘧啶芥和6-乙基尿嘧啶芥。
• NOVEL QUINOLINE COMPOUND AND USE THEREOF
  申请人：MBD CO., LTD.

  公开号：US20220402890A1

  公开（公告）日：2022-12-22

  The present invention relates to a novel quinoline compound and a use thereof and to a novel quinoline compound exhibiting CYP4A inhibition activity and a use thereof for preventing, alleviating, treating a metabolic disease. The compound disclosed in the present invention has a remarkable effect of inhibiting CYP4A and exhibits the activities of promoting the absorption of glucose into hepatocytes, inhibiting fat accumulation in hepatocytes, suppressing endoplasmic reticulum-induced reactive oxygen species, and treating steatohepatitis, and thus can be very advantageously used for developing therapeutics for metabolic diseases such as diabetes mellitus and fatty liver.

  本发明涉及一种新型喹啉化合物及其用途，以及一种表现出CYP4A抑制活性的新型喹啉化合物及其用途，用于预防、缓解、治疗代谢性疾病。本发明所披露的化合物具有显著的抑制CYP4A的效果，并表现出促进葡萄糖吸收到肝细胞中，抑制肝细胞中脂肪积累，抑制内质网诱导的反应性氧化物种，以及治疗脂肪肝等活性，并因此可以非常有利地用于开发治疗糖尿病和脂肪肝等代谢性疾病的药物。
• COMPOSITION COMPRISING CYP4A-INHIBITING COMPOUND AS ACTIVE INGREDIENT FOR PREVENTING OR TREATING METABOLIC DISEASES
  申请人：Korea Basic Science Institute

  公开号：EP3900725A1

  公开（公告）日：2021-10-27

  The present invention relates to a composition comprising a CYP4A-inhibiting compound as an active ingredient for preventing or treating metabolic diseases, more specifically to a composition comprising the compound expressed by chemical formula 1 of the present invention or pharmaceutically acceptable salt thereof as an active ingredient for preventing, ameliorating or treating metabolic diseases.

  本发明涉及一种包含 CYP4A 抑制化合物的组合物，作为预防或治疗代谢性疾病的活性成分，更具体地说，涉及一种包含本发明化学式 1 所表示的化合物或其药学上可接受的盐的组合物，作为预防、改善或治疗代谢性疾病的活性成分。
• Pharmaceutical composition for prevention or treatment of diabetes or fatty liver comprising CYP4A inhibitor
  申请人：KOREA BASIC SCIENCE INSTITUTE

  公开号：US10166223B2

  公开（公告）日：2019-01-01

  The present invention relates to a pharmaceutical composition for the prevention or treatment of diabetes or fatty liver comprising a CYP4A (cytochrome P450A) inhibitor as an active ingredient. The compound of the present invention has activities of promoting glucose uptake into hepatocytes, inhibiting fat accumulation in liver cells, and inhibiting reactive oxygen production in mitochondria, and thus can be very usefully used for the development of a therapeutic agent for diabetes or fatty liver.

  本发明涉及一种用于预防或治疗糖尿病或脂肪肝的药物组合物，其中包含一种 CYP4A（细胞色素 P450A）抑制剂作为活性成分。本发明的化合物具有促进肝细胞摄取葡萄糖、抑制肝细胞内脂肪堆积和抑制线粒体内活性氧产生的活性，因此可非常有益地用于开发糖尿病或脂肪肝的治疗剂。