3-氰基苯肼盐酸盐 | 2881-99-4

• 物质功能分类: 化学试剂 - 有机试剂 - 肼
• 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: 3-氰基苯肼盐酸盐
• 中文别名: 间氰基苯肼盐酸盐
• 英文名称: 3-cyano-phenylhydrazine hydrochloride
• 英文别名: 3-hydrazinylbenzonitrile hydrochloride；3-Cyanophenylhydrazine hydrochloride；3-hydrazinylbenzonitrile;hydrochloride
• CAS: 2881-99-4
• 化学式: C₇H₇N₃*ClH
• 分子量: 169.614
• InChiKey: OLRXCKFWRROJFZ-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.87
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  3-氰基苯肼盐酸盐 在 lithium hydroxide 、 草酰氯 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 44.0h， 生成 1-(3-cyanophenyl)-N-[2'-(tert-butylaminosulfonyl) [1,1'-biphenyl]-4-yl]-3-methyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Discovery of 1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2‘-(methylsulfonyl)- [1,1‘-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a Highly Potent, Selective, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

  摘要：

  Factor Xa (fXa) plays a critical role in the coagulation cascade, serving as the point of convergence of the intrinsic and extrinsic pathways. Together with nonenzymatic cofactor Va and Ca2+ on the phospholipid surface of platelets or endothelial cells, factor Xa forms the prothrombinase complex, which is responsible for the proteolysis of prothrombin to catalytically active thrombin. Thrombin, in turn, catalyzes the cleavage of fibrinogen to fibrin, thus initiating a process that ultimately leads to clot formation. Recently, we reported on a series of isoxazoline and isoxazole monobasic noncovalent inhibitors of factor Xa which show good potency in animal models of thrombosis. In this paper, we wish to report on the optimization of the heterocyclic core, which ultimately led to the discovery of a novel pyrazole SN429 (2b; fXa K-i = 13 pM). We also report on our efforts to improve the oral bioavailability and pharmacokinetic profile of this series while maintaining subnanomolar potency and in vitro selectivity. This was achieved by replacing the highly basic benzamidine P-1 with a less basic benzylamine moiety. Further optimization of the pyrazole core substitution and the biphenyl P-4 culminated in the discovery of DPC423 (17h), a highly potent, selective, and orally active factor Xa inhibitor which was chosen for clinical development.

  DOI：

  10.1021/jm000409z
• 作为产物：
  描述：

  间碘苯腈 在 potassium phosphate 、 copper(l) iodide 、 N,N'-二(2,6-二甲基苯基)草酰胺 、 十六烷基三甲基溴化铵 、 一水合肼 、 盐酸 作用下， 以 水 为溶剂， 反应 0.25h， 以65%的产率得到3-氰基苯肼盐酸盐
  参考文献：
  名称：

  CuI / BMPO催化卤代芳烃与水合肼的交叉偶联合成芳族肼

  摘要：

  的N，N-双（2,6-二甲基苯基）草酰胺，发现作为一个强大的配体对Cu催化的与水合肼芳基卤化物的交叉耦合，从而导致的各种芳基肼的形成在80 ö用C在K 3 PO 4和4 mol％的十六烷基三甲基溴化铵的帮助下，从芳基溴化物和芳基碘化物中加入水。在大多数情况下，观察到良好至极好的产量。

  DOI：

  10.1002/cjoc.201800326

文献信息

• Continuous Flow Process For the Synthesis of Phenylhydrazine Salts and Substituted Phenylhydrazine Salts
  申请人：SHANGHAI HYBRID-CHEM TECHNOLOGIES

  公开号：US20190152896A1

  公开（公告）日：2019-05-23

  The present invention provided a continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts. Diazotization, reduction, acidic hydrolysis and salifying with acids are innovatively integrated together. Using acidic liquids of aniline or substituted aniline, diazotization reagents, reductants and acids as raw materials, phenylhydrazine derivative salts is obtained through the synthesis process, which is a three-step continuous tandem reaction including diazotization, reduction, acidic hydrolysis and salifying. The described synthesis process is a kind of integrated solutions, which is carried out in an integrated reactor. The feed inlets of the integrated reactor are continuously filled with raw materials. In the integrated reactor, diazotization, reduction, acidic hydrolysis and salifying are carried out continuously and orderly, and phenylhydrazine salts or substituted phenylhydrazine salts is obtained in the outlet of the integrated reactor without interruption. The total reaction time is no more than 20 min.

  本发明提供了一种连续流程，用于合成苯肼盐和取代苯肼盐。重氮化、还原、酸性水解和酸化与酸类创新地集成在一起。使用苯胺或取代苯胺的酸性液体、重氮化试剂、还原剂和酸类作为原料，通过合成过程获得苯肼衍生物盐，这是一个包括重氮化、还原、酸性水解和酸化的三步连续串联反应。所述的合成过程是一种集成解决方案，是在一个集成反应器中进行的。集成反应器的进料口连续填充原料。在集成反应器中，重氮化、还原、酸性水解和酸化被连续有序地进行，苯肼盐或取代苯肼盐在集成反应器的出口处获得，没有中断。总反应时间不超过20分钟。
• Design, Synthesis and Study of Antibacterial and Antitubercular Activity of Quinoline Hydrazone Hybrids
  作者：Shruthi T G、Sangeetha Subramanian、Sumesh Eswaran

  DOI：10.1515/hc-2020-0109

  日期：2020.10.15

  various infections. Therefore, the search for antimicrobials is a never-ending task. Hydrazones and quinolines possess a wide variety of biological activities. Herewith, eleven quinoline hydrazone derivatives have been designed, synthesized, characterized and evaluated for their antibacterial activity and antitubercular potential against Mtb WT H37Rv. Compounds QH-02, QH-04 and QH-05 were found to be

  摘要 新出现的细菌耐药性给各种感染的治疗带来了广泛的问题。因此，寻找抗菌药物是一项永无止境的任务。腙和喹啉具有多种生物活性。因此，已经设计、合成、表征和评估了 11 种喹啉腙衍生物的抗菌活性和对 Mtb WT H37Rv 的抗结核潜力。发现化合物 QH-02、QH-04 和 QH-05 是有前途的化合物，对 Mtb WT H37Rv 的 MIC 值为 4 μg/mL。还发现化合物 QH-02、QH-04、QH-05 和 QH-11 对包括鲍曼不动杆菌、大肠杆菌和金黄色葡萄球菌在内的细菌菌株具有活性。更多，
• Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
  作者：Jakob S. Pallesen、Dilip Narayanan、Kim T. Tran、Sara M. Ø. Solbak、Giuseppe Marseglia、Louis M. E. Sørensen、Lars J. Høj、Federico Munafò、Rosa M. C. Carmona、Anthony D. Garcia、Haritha L. Desu、Roberta Brambilla、Tommy N. Johansen、Grzegorz M. Popowicz、Michael Sattler、Michael Gajhede、Anders Bach

  DOI：10.1021/acs.jmedchem.0c02094

  日期：2021.4.22

  Keap1–Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220–380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic

  靶向核因子类红细胞2相关因子2（Nrf2）和与Kelch样ECH相关蛋白1（Keap1）之间的蛋白相互作用是控制涉及氧化应激疾病的潜在治疗策略。在这里，在基于片段的解构重建（FBDR）研究中，将六类已知的小分子Keap1-Nrf2 PPI抑制剂分解为77个片段，并在四个正交试验中进行了测试。这给出了17个片段命中，其中X射线晶体学显示其中6个在Keap1 Kelch结合袋中结合。相对于亲本片段，两个命中片段以220-380倍的亲和力（K i = 16μM）被合并到化合物8中。系统优化产生了一些与K i有关的新颖类似物值0.04–0.5μM，通过X射线晶体学测定的结合模式，以及增强的微粒体稳定性。这证明了FBDR如何可用于发现新的片段片段，阐明重要的配体-蛋白质相互作用以及鉴定Keap1-Nrf2 PPI的新有效抑制剂。
• Denitrogenative Pd/Cu‐catalyzed Suzuki‐type Cross‐coupling of Aryltrifluoroborates with Arylhydrazine Hydrochlorides in Water under Room Temperature
  作者：Guofang Wang、Mengting Meng、Liping Deng、Kai Cheng、Chenze Qi

  DOI：10.1002/aoc.4203

  日期：2018.3

  A water‐soluble palladium‐catalyzed Suzuki‐type cross‐coupling of aryltrifluoroborates with arylhydrazide hydrochlorides was efficiently developed under mild and environmentally benign conditions, in water without any ligand. The newly developed Pd/Cu co‐catalyzed denitrogenative reaction gave a range of structurally diverse substituted biaryls with good to excellent yields, in which the byproduct

  在温和，无害于环境的条件下，在没有任何配体的水中，水溶性钯催化的三氟硼酸芳基酯与芳酰肼盐酸盐的水溶性钯催化交叉偶联反应得到了有效开发。新开发的Pd / Cu共催化脱氮反应产生了一系列结构多样的取代联芳基，其收率良好至极佳，其中副产品为氮。
• Nitrogen containing heteroaromatics as factor Xa inhibitors
  申请人：DuPont Pharmaceuticals Company

  公开号：US06020357A1

  公开（公告）日：2000-02-01

  The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: ##STR1## or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is N or NH and D may be C(.dbd.NH)NH.sub.2, which are useful as inhibitors of factor Xa.

  本申请描述了具有以下式I的含氮杂芳烃及其衍生物：##STR1##或其药用可接受的盐或前药形式，其中J为N或NH，D可以是C(.dbd.NH)NH.sub.2，这些化合物可用作因子Xa的抑制剂。