3,3′-(4-methoxyphenylazanediyl)dipropanehydrazide | 56682-33-8

• 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: 3,3′-(4-methoxyphenylazanediyl)dipropanehydrazide
• 英文别名: 3,3'-((4-methoxyphenyl)azanediyl)di(propanehydrazide)；N-(p-Methoxyphenyl)iminodipropionsaeuredihydrazid；3-(N-(3-hydrazinyl-3-oxopropyl)-4-methoxyanilino)propanehydrazide
• CAS: 56682-33-8
• 化学式: C₁₃H₂₁N₅O₃
• 分子量: 295.341
• InChiKey: XFNJSYASSJFNFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,3′-(4-methoxyphenylazanediyl)dipropanehydrazide 在 盐酸 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 26.0h， 生成 3,3′-(2,2′-(4-methoxyphenylazanediyl)bis(ethane-2,1-diyl))-bis-(4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide)
  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
• 作为产物：
  描述：

  dimethyl 3,3′-(4-methoxyphenylazanediyl)dipropanoate 在 一水合肼 作用下， 以 异丙醇 为溶剂， 反应 48.0h， 以95%的产率得到3,3′-(4-methoxyphenylazanediyl)dipropanehydrazide
  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)
• Synthesis of azoles from 3,3′-[(4-alkoxyphenyl)imino]bis(propanoic acid hydrazides)
  作者：Ingrida Tumosienė、Zigmuntas Jonas Beresnevičius

  DOI：10.1007/s00706-009-0210-y

  日期：2009.12

  AbstractReaction of 3,3′-[(4-alkoxyphenyl)imino]bis(propanoic acid hydrazides) with CS2 in alkaline solution and subsequent acidification gave 5,5′-[[(4-alkoxyphenyl)imino]diethane-2,1-diyl]bis(1,3,4-oxadiazole-2(3H)-thiones). The same dihydrazides on reaction with phenyl isocyanates or phenyl isothiocyanates were converted to bis[N′-(phenylaminocarbonyl)propanoic acid hydrazides] and bis[N′-(phenylaminoc

  摘要3,3'-[（（4-烷氧基苯基）亚氨基]双丙酸酰肼）与CS 2在碱性溶液中反应，然后酸化，得到5,5'-[[（4-烷氧基苯基）亚氨基]二乙烷-2,1 -二基]双（1,3,4-恶二唑-2（3 H）-硫酮）。与苯基异氰酸酯或苯基异硫氰酸酯反应时将相同的二酰肼转化为双[ N '-（苯基氨基羰基）丙酸酰肼]和双[ N '-（苯基氨基羰基硫代羰基）丙酸酰肼]，并在碱性介质中进行环化反应生成5， 5'-[[（（4-烷氧基苯基）亚氨基]二乙烷-2,1-二基]双（4-苯基-2,4-二氢-3 H -1,2,4-三唑-3-酮）及其3 -硫代类似物，而在硫酸或POCl 3中5,5'-[[（（4-烷氧基苯基）亚氨基]二乙烷-2,1-二基]双（N-苯基-1,3,4-恶二唑-2-胺）和5,5'-[[（4得到-（烷氧基苯基）亚氨基]二乙烷-2,1-二基]双（N-苯基-1,3,4-噻二唑-2-胺）。 图形概要