1-nicotinyl-1-methylhydrazine | 89812-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-nicotinyl-1-methylhydrazine
• 英文别名: N-methylnicotinohydrazide；1-Methyl-1-nicotinoyl hydrazine；N'-methylpyridine-3-carbohydrazide；N-methylpyridine-3-carbohydrazide
• CAS: 89812-16-8
• 化学式: C₇H₉N₃O
• 分子量: 151.168
• InChiKey: CFOCBLCVQJMSDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-nicotinyl-1-methylhydrazine 在 哌啶 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 N-methyl-N-[(E)-(6-phenylmethoxy-7H-purin-2-yl)diazenyl]pyridine-3-carboxamide
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Methyltriazene Prodrugs Simultaneously Releasing DNA-Methylating Agents and the Antiresistance Drug O⁶-Benzylguanine

  摘要：

  Active resistance of tumor cells against DNA alkylating agents arises by the production of high levels of the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT). This resistance during treatment with, for example, the anticancer agent temozolomide can be reversed by administration of O-6-benzylguanine, a purine that transfers its benzyl group to AGT and irreversibly inactivates it. Stimulated by the favorable therapeutic properties of temozolomide we designed and synthesized DNA-methylating triazenes built on the anti-resistance benzylguanine ring system. The condensation reaction between 2-nitrosopurines and acylhydrazines proved to be very suitable to prepare acylated methyltriazenes. Fine-tuning of the release rate of both the methylating agent (diazomethane) and of O-6-benzylguanine was accomplished by variation of the hydrolysis-sensitive acyl substituent in 5. Hydrolysis studies were performed with H-1 NMR and revealed that the p-nitrophenyl substituted triazene 26 showed an optimal hydrolysis rate (t(1/2) = 23 min) and almost 100% selectivity for the desired fragmentation route. In vitro antitumor studies in the 60 human tumor cell line panel of the National Cancer Institute confirmed the superior properties of p-nitrophenyl-protected methyl triazene 26, showing mean IC50 values of 10 muM compared to 100 muM for temozolomide. In analogy with temozolomide, triazene 26 showed however low preference for each of the cancer subpanels, with IC50 values between 8 and 14 muM.

  DOI：

  10.1021/jm049556d
• 作为产物：
  描述：

  烟酰氯 、 甲基肼 以 二氯甲烷 为溶剂， 反应 3.0h， 以40%的产率得到1-nicotinyl-1-methylhydrazine
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Methyltriazene Prodrugs Simultaneously Releasing DNA-Methylating Agents and the Antiresistance Drug O⁶-Benzylguanine

  摘要：

  Active resistance of tumor cells against DNA alkylating agents arises by the production of high levels of the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT). This resistance during treatment with, for example, the anticancer agent temozolomide can be reversed by administration of O-6-benzylguanine, a purine that transfers its benzyl group to AGT and irreversibly inactivates it. Stimulated by the favorable therapeutic properties of temozolomide we designed and synthesized DNA-methylating triazenes built on the anti-resistance benzylguanine ring system. The condensation reaction between 2-nitrosopurines and acylhydrazines proved to be very suitable to prepare acylated methyltriazenes. Fine-tuning of the release rate of both the methylating agent (diazomethane) and of O-6-benzylguanine was accomplished by variation of the hydrolysis-sensitive acyl substituent in 5. Hydrolysis studies were performed with H-1 NMR and revealed that the p-nitrophenyl substituted triazene 26 showed an optimal hydrolysis rate (t(1/2) = 23 min) and almost 100% selectivity for the desired fragmentation route. In vitro antitumor studies in the 60 human tumor cell line panel of the National Cancer Institute confirmed the superior properties of p-nitrophenyl-protected methyl triazene 26, showing mean IC50 values of 10 muM compared to 100 muM for temozolomide. In analogy with temozolomide, triazene 26 showed however low preference for each of the cancer subpanels, with IC50 values between 8 and 14 muM.

  DOI：

  10.1021/jm049556d

文献信息

• [EN] TRIAZOLE AGONISTS OF THE APJ RECEPTOR<br/>[FR] TRIAZOLES AGONISTES DU RÉCEPTEUR APJ
  申请人：AMGEN INC

  公开号：WO2016187308A1

  公开（公告）日：2016-11-24

  Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures where the definitions of the variables are provided herein.

  公式I和公式II的化合物，其药用盐，上述任何一种的立体异构体，或它们的混合物是APJ受体的激动剂，并可用于治疗心血管和其他疾病。公式I和公式II的化合物具有以下结构，其中变量的定义在此提供。
• [EN] INDAZOLONES AS MODULATORS OF TNF SIGNALING<br/>[FR] INDAZOLONES UTILISÉES EN TANT QUE MODULATEURS DE LA SIGNALISATION DU TNF
  申请人：ABBVIE INC

  公开号：WO2016168633A1

  公开（公告）日：2016-10-20

  The disclosure provides indazolone compounds, pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variables are defined herein. The compounds of the disclosure may be useful for treating immunological and oncological conditions.

  该披露提供了吲唑酮化合物、药用可接受的盐、前药、生物活性代谢物、立体异构体和同分异构体，其中变量在此处定义。该披露的化合物可能对治疗免疫和肿瘤疾病有用。
• Synthesis of Sulfonylhydrazone- and Acylhydrazone-Substituted 8-Ethoxy-3-nitro-2<i>H</i>-chromenes as Potent Antiproliferative and Apoptosis Inducing Agents
  作者：Datong Zhang、Yuntong Ma、Yu Liu、Zhao-Peng Liu

  DOI：10.1002/ardp.201400082

  日期：2014.8

  K562 cells at the G1 phase at high concentrations and induced apoptosis in K562 cells. Furthermore, 7d increased the levels of cleaved caspase‐3, decreased the expression of bcl‐2 and induced the cleavage of poly(ADP‐ribose) polymerase in K562 cells. Thus, this study provides the development of a series of novel compounds as effective antitumor agents with apoptotic death ability.

  3-硝基-2H-色烯最近被鉴定为一类新型的强效抗肿瘤剂。鉴于磺酰腙和酰腙显示出的良好效果，我们设计合成了一系列磺酰腙和酰腙取代的8-乙氧基-3-硝基-2H-色烯衍生物，并评估了它们对A549、KG-的细胞生长抑制活性。 1、A2780 和 K562 细胞。所有测试的化合物对 KG-1 细胞都表现出比 BENC-511 更强的抗增殖活性。这些化合物对 A2780 细胞显示出纳摩尔范围内的 IC50 值。化合物 7d 对 K562 细胞显示出显着的细胞毒性，IC50 为 0.11 µM，与 BENC-511 相当。化合物 7d 以高浓度将 K562 细胞阻滞在 G1 期并诱导 K562 细胞凋亡。此外，7d 增加裂解的 caspase-3 的水平，降低 bcl-2 的表达并诱导 K562 细胞中聚（ADP-核糖）聚合酶的裂解。因此，本研究提供了一系列新型化合物作为具有凋亡死亡能力的有效抗肿瘤剂的开发。
• 7-Oxabicycloheptane hydrazone prostaglandin analogs useful in treating
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04418076A1

  公开（公告）日：1983-11-29

  7-Oxabicycloheptane hydrazone prostaglandin analogs are provided having the structural formula ##STR1## and including all stereoisomers thereof. pa The compounds are cardiovascular agents useful, for example, in the treatment of thrombolytic disease.

  提供了具有结构式##STR1##的7-Oxabicycloheptane hydrazone前列腺素类似物，包括所有立体异构体。这些化合物是心血管药物，例如在溶栓疾病的治疗中很有用。
• TRIAZOLE AGONISTS OF THE APJ RECEPTOR
  申请人：AMGEN INC.

  公开号：US20170044131A1

  公开（公告）日：2017-02-16

  Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

  公式I和公式II的化合物，其药用可接受的盐，任何上述的立体异构体，或其混合物均为APJ受体激动剂，并可用于治疗心血管和其他疾病。公式I和公式II的化合物具有以下结构：其中变量的定义在此处提供。