2-(4-氧代-3,4-二氢-1-酞嗪)乙酰肼 | 25947-18-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-(4-氧代-3,4-二氢-1-酞嗪)乙酰肼
• 中文别名: 2-(4-氧代-3H-酞嗪-1-基)乙烷肼
• 英文名称: 2-(1,2-dihydro-1-oxophthalazin-4-yl)acetohydrazide
• 英文别名: 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetohydrazide；(4-oxo-3,4-dihydro-phthalazin-1-yl)-acetic acid hydrazide；Phthalazon-4-yl-1-essigsaeure-hydrazid；2-(4-oxo-3H-phthalazin-1-yl)acetohydrazide
• CAS: 25947-18-6
• 化学式: C₁₀H₁₀N₄O₂
• mdl: MFCD01309894
• 分子量: 218.215
• InChiKey: LRYHCCVJXQEMLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  96.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(4-氧代-3,4-二氢-1-酞嗪)乙酰肼 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N'-(2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetyl)-4-phenylthiazole-2-carbohydrazide
  参考文献：
  名称：

  Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

  摘要：

  With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC50 of 0.07 +/- 0.02 mu M) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-gamma agonist activity thus making it a very interesting scaffold. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.067
• 作为产物：
  描述：

  2-(4-氧-3,4-二氢邻苯二甲秦)乙酸 在 一水合肼 作用下， 反应 0.5h， 以70%的产率得到2-(4-氧代-3,4-二氢-1-酞嗪)乙酰肼
  参考文献：
  名称：

  Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

  摘要：

  With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC50 of 0.07 +/- 0.02 mu M) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-gamma agonist activity thus making it a very interesting scaffold. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.067

文献信息

• Rational modification, synthesis and biological evaluation of N-substituted phthalazinone derivatives designed to target interleukine-15 protein
  作者：Jimmy Smadja、Agnès Quéméner、Mike Maillasson、Benoit Sicard、Aurélien Leray、Laurence Arzel、Jacques Lebreton、Erwan Mortier、Didier Dubreuil、Monique Mathé-Allainmat

  DOI：10.1016/j.bmc.2021.116161

  日期：2021.6

  Interleukin (IL)-15 is a pleiotropic cytokine structurally close to IL-2 and sharing with the IL-2Rβ and γc receptor (R) subunits. IL-15 plays important roles in innate and adaptative immunity, supporting the activation and proliferation of NK, NK-T, and CD8+ T cells. Over-expression of IL-15 has been shown to participate to the development of inflammatory and autoimmune diseases and diverse T cell

  白细胞介素 (IL)-15 是一种多效性细胞因子，在结构上与 IL-2 接近，并与 IL-2Rβ 和 γc 受体 (R) 亚基共享。IL-15 在先天性和适应性免疫中发挥重要作用，支持 NK、NK-T 和 CD8 +的激活和增殖T细胞。IL-15 的过度表达已被证明参与炎症和自身免疫性疾病以及多种 T 细胞恶性肿瘤的发展。这项研究延续了我们之前的工作，通过基于药效团的虚拟筛选和命中优化方法，已经确定了一系列阻碍 IL-15/IL-2Rβ 与亚微摩尔活性相互作用的小分子抑制剂。为了提高我们先导抑制剂的功效和选择性，在优化的 SAR 和建模的基础上引入了特定的修改。已经评估了产生的新系列化合物抑制 IL-15 依赖性细胞的增殖和下游信号传导以及与 IL-15 结合的能力。
• ABDEL-FATTAH, B.;AL-ASHMAWI, M. I.;EL-FEKY, S.;RODER, E., EGYPT. J. PHARM. SCI., 29,(1988) N-4, C. 259-268
  作者：ABDEL-FATTAH, B.、AL-ASHMAWI, M. I.、EL-FEKY, S.、RODER, E.

  DOI：——

  日期：——
• EL-FATTAH, B. ABD;ROEDER, E.;AL-ASHMAWI, M. I.;EL-FEKY, S., EGYPT. J. PHARM. SCI., 28,(1987) N 1-4, 371-382
  作者：EL-FATTAH, B. ABD、ROEDER, E.、AL-ASHMAWI, M. I.、EL-FEKY, S.

  DOI：——

  日期：——
• Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening
  作者：Madhavi Agrawal、Prashant Kharkar、Sonali Moghe、Tushar Mahajan、Vaishali Deka、Chandni Thakkar、Amrutha Nair、Chirag Mehta、Julie Bose、Asha Kulkarni-Almeida、Dilip Bhedi、Ram A. Vishwakarma

  DOI：10.1016/j.bmcl.2013.07.067

  日期：2013.10

  With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC50 of 0.07 +/- 0.02 mu M) in differentiated skeletal muscle cells in presence of insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-gamma agonist activity thus making it a very interesting scaffold. (C) 2013 Elsevier Ltd. All rights reserved.