N-(4-methylphenyl)iminodipropanoyl dihydrazide | 71900-89-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(4-methylphenyl)iminodipropanoyl dihydrazide
• 英文别名: 3,3'-(p-tolylazanediyl)di(propanehydrazide)；3,3'‑(p‑tolylazanediyl)di(propanehydrazide)；N-(p-Tolyl)-iminodipropionsaeuredihydrazid；3-(N-(3-hydrazinyl-3-oxopropyl)-4-methylanilino)propanehydrazide
• CAS: 71900-89-5
• 化学式: C₁₃H₂₁N₅O₂
• 分子量: 279.342
• InChiKey: PRSBKUFBJDLJFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  114
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-methylphenyl)iminodipropanoyl dihydrazide 在 溶剂黄146 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 N-(4-methylphenyl)iminodipropanoyl diazide
  参考文献：
  名称：

  Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

  摘要：

  The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide.

  DOI：

  10.1021/ml300132t
• 作为产物：
  描述：

  乙烷,三氯氟- 在 一水合肼 、 溶剂黄146 、 copper(l) chloride 作用下， 以 异丙醇 为溶剂， 反应 96.0h， 生成 N-(4-methylphenyl)iminodipropanoyl dihydrazide
  参考文献：
  名称：

  Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair, and p53

  摘要：

  The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR, and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bifunctional analogues are reported, and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bifunctional congener as optimized for potency, MGMT-independence, and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development, and their improved in vitro activity validates the principles on which they were designed.

  DOI：

  10.1021/jm401121k

文献信息

• [EN] AMINOALYL-IMIDAZOTETRAZINES FOR TREATMENT OF CANCER<br/>[FR] AMINOALLYLIMIDAZOTÉTRAZINES POUR LE TRAITEMENT DE CANCERS
  申请人：UNIV BRADFORD

  公开号：WO2009127815A1

  公开（公告）日：2009-10-22

  The present invention relates to imidazotetrazines of Formula (I) and their use in the treatment of cancer.

  本发明涉及式(I)的咪唑四嗪及其在治疗癌症中的用途。
• Novel N-Substituted Amino Acid Hydrazone-Isatin Derivatives: Synthesis, Antioxidant Activity, and Anticancer Activity in 2D and 3D Models In Vitro
  作者：Ingrida Tumosienė、Ilona Jonuškienė、Kristina Kantminienė、Vytautas Mickevičius、Vilma Petrikaitė

  DOI：10.3390/ijms22157799

  日期：——

  or diphenylamine fragments were synthesized, and their anticancer activities were tested by MTT assay against human melanoma A375 and colon adenocarcinoma HT-29 cell lines. In general, the synthesized compounds were more cytotoxic against HT-29 than A375. 3-((4-Methoxyphenyl)(3-oxo-3-(2-(2-oxoindolin-3-ylidene)hydrazinyl)propyl)amino)-N’-(2-oxoindolin-3-ylidene)propanehydrazide and (N’,N’’’)-1,1’-(methylenebis(4

  合成了一系列新的单腙和双腙，每个都带有 2-羟吲哚部分以及取代的苯氨基丙酰胺、吡咯烷-2-one、苯并咪唑、二苯甲烷或二苯胺片段，并通过 MTT 法测试了它们对人黑色素瘤 A375 和结肠的抗癌活性腺癌 HT-29 细胞系。一般来说，合成的化合物对 HT-29 的细胞毒性比 A375 更强。3-((4-甲氧基苯基)(3-oxo-3-(2-(2-oxoindolin-3-ylidene)hydrazinyl)丙基)amino) -N '-(2-oxoindolin-3-ylidene)丙酰肼和( N ', N ''')-1,1'-(亚甲基双(4,1-亚苯基))双(5-氧代-N'-(2-oxoindolin-3-ylidene)pyrrolidine-3-carbohydrazide) 被鉴定为在 2D 和 3D 细胞培养物中对抗 HT-29 的最活性化合物。在通过铁还原抗氧化能力测定 (FRAP)
• The synthesis of disubstituted 4-methyl-N,N-dipropylbenzenamine derivatives bearing identical azolethione(thiol) moieties as antioxidant agents
  作者：Ingrida Tumosienė、Ilona Jonuškienė、Sergey Belyakov、Kristina Kantminienė

  DOI：10.1007/s00706-023-03119-7

  日期：2023.10

  and hydrazone moieties were synthesized and their molecular structures were confirmed by IR, 1H, 13C NMR spectroscopy and mass spectrometry data. X-ray analysis of 2,2'-[[[(p-tolylazanediyl)bis(ethane-2,1-diyl)]bis(4-phenyl-4H-1,2,4-triazole-5,3-diyl)]bis(sulfanediyl)]bis[1-(p-tolyl)ethan-1-one] crystal has revealed, that the molecules in the crystal are associated by means of intermolecular hydrogen

  合成了一系列带有双组氨基硫脲、恶二唑硫酮、不同N-和S-取代的三唑硫酮、吡咯和腙部分的新型3,3'-(对甲苯氮烷二基)二(丙酰肼)衍生物，并通过以下方法证实了它们的分子结构：IR、1 H、13 C NMR 光谱和质谱数据。2,2'-[[[(对甲苯氮烷二基)双(乙烷-2,1-二基)]双(4-苯基-4 H -1,2,4-三唑-5,3-)的X射线分析二基)]双(硫基)]双[1-( p(-tolyl)ethan-1-one]晶体表明，晶体中的分子通过OH·N型分子间氢键缔合，形成中心对称二聚体。通过DPPH自由基清除测定、还原力测定和铁还原抗氧化力测定来筛选合成化合物的抗氧化活性。在合成的化合物中，2,2'-[3,3'-(对甲苯氮烷二基)双(丙酰基)]双( N-苯肼-1-硫代甲酰胺)被认为具有最高的抗氧化活性，其抗氧化活性为1.25–比商业抗氧化剂丁基羟基甲苯高2倍。 图形概要
• Synthesis of azoles from 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides
  作者：I. Tumosiene、Z. I. Beresnevicius

  DOI：10.1007/s10593-007-0176-9

  日期：2007.9
• Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR
  作者：Elrashied A. E. Garelnabi、Dimitrios Pletsas、Li Li、Konstantinos Kiakos、Nazira Karodia、John A. Hartley、Roger M. Phillips、Richard T. Wheelhouse

  DOI：10.1021/ml300132t

  日期：2012.12.13

  The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide.