3-N-(methylamino)-4-nitrobenzonitrile | 64910-48-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-N-(methylamino)-4-nitrobenzonitrile
• 英文别名: 3-methylamino-4-nitrobenzonitrile；3-methylamino-4-nitro-benzonitrile；3-Methylamino-4-nitro-benzonitril；3-(methylamino)-4-nitrobenzonitrile；3-Methylamino-4-nitrobenzonitril
• CAS: 64910-48-1
• 化学式: C₈H₇N₃O₂
• 分子量: 177.162
• InChiKey: NEYPCGNVBGKPTF-UHFFFAOYSA-N

物化性质

• 熔点：
  213-214 °C
• 沸点：
  364.2±37.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-N-(methylamino)-4-nitrobenzonitrile 在 盐酸 、 铁粉 作用下， 以 乙醇 、 水 为溶剂， 生成 4-氨基-3-甲基氨基苯甲腈
  参考文献：
  名称：

  Cu催化苯并咪唑与艾伦的C-H烯丙基化

  摘要：

  已经描述了 CuH 催化的苯并咪唑与丙二烯的分子内环化和分子间烯丙基化。在Cu(OAc) 2 /Xantphos的催化体系和催化量的(MeO) 2 MeSiH的作用下，反应顺利进行。该协议具有温和的反应条件和对带有吸电子、给电子或电子中性基团的底物的良好耐受性。针对该氢化铜催化体系提出了一种新的催化机理。

  DOI：

  10.1021/acs.orglett.1c02346
• 作为产物：
  描述：

  3-甲氧基-4-硝基苯甲酰氯 在 氨 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 3.0h， 生成 3-N-(methylamino)-4-nitrobenzonitrile
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638

文献信息

• Substituted Fused Imidazole Derivatives, Pharmaceutical Compositions, and Methods of Use Thereof
  申请人：Mjalli Adnan M. M.

  公开号：US20110201604A1

  公开（公告）日：2011-08-18

  Substituted fused imidazole derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted fused imidazole derivative, and methods of use in treating inflammation are provided. The substituted fused imidazole derivatives may control the activity or the amount or both the activity and the amount of heme-oxygenase.

  提供了替代融合咪唑衍生物、其制备方法、包含替代融合咪唑衍生物的药物组合物，以及在治疗炎症中使用的方法。这些替代融合咪唑衍生物可能控制血红素氧合酶的活性或数量，或者同时控制活性和数量。
• [EN] ALDOSTERONE SYNTHASE INHIBITORS<br/>[FR] INHIBITEURS DE L'ALDOSTÉRONE SYNTHASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012012478A1

  公开（公告）日：2012-01-26

  The invention involves compounds of structural Formula (I) and the pharmaceutically acceptable salts thereof. The compounds of the invention are effective at selectively inhibiting CYP11B2, and are therefore useful for the treatment or prophylaxis of disorders that are associated with elevated aldosterone levels, including, but not limited to, hypertension and heart failure.

  该发明涉及结构式（I）的化合物及其药用盐。该发明的化合物在选择性抑制CYP11B2方面具有有效性，因此可用于治疗或预防与升高醛固酮水平相关的疾病，包括但不限于高血压和心力衰竭。
• N-substituted benzimidazole acrylonitriles as in vitro tubulin polymerization inhibitors: Synthesis, biological activity and computational analysis
  作者：N. Perin、L. Hok、A. Beč、L. Persoons、E. Vanstreels、D. Daelemans、R. Vianello、M. Hranjec

  DOI：10.1016/j.ejmech.2020.113003

  日期：2021.2

  antiproliferative activity in vitro on eight human cancer cell lines and one reference non-cancerous assay. N,N-dimethylamino substituted acrylonitriles 30 and 41, bearing N-isobutyl and cyano substituents placed on the benzimidazole nuclei, showed strong and selective antiproliferative activity in the submicromolar range of inhibitory concentrations (IC50 0.2 – 0.6 μM), while being significantly less

  我们提出了新型的N-取代的苯并咪唑基丙烯腈作为微管蛋白聚合的潜在抑制剂的设计，合成和生物活性。它们的合成是使用经典的线性有机和微波辅助技术完成的，从芳香醛和N-取代的2-氰基甲基苯并咪唑类化合物开始。所有新制备的化合物均在八种人类癌细胞系中进行了体外抗增殖活性的测试，并在一项非癌性参考测定中进行了测试。N，N-二甲基氨基取代的丙烯腈30和41，含N苯并咪唑核上的-异丁基和氰基取代基在亚微摩尔浓度的抑制浓度下（IC 50 0.2 – 0.6μM）显示出强而有选择性的抗增殖活性，但毒性明显低于参考系统多西他赛和星形孢菌素，因此促进它们作为铅化合物。作用机理研究表明，两种活性最高的化合物抑制微管蛋白的聚合。计算分析证实所用的苯并咪唑-丙烯腈骨架适合于微管蛋白中秋水仙碱结合位点内的结合，从而使观察到的抗肿瘤活性合理化，并证明了E-异构体是活性物质。它还提供了影响结合位置和匹配亲和力的结构决定因素，确定了附着的NMe
• [EN] NOVEL CHEMICAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005082901A1

  公开（公告）日：2005-09-09

  This invention relates to newly identified compounds for inhibiting hYAK3 proteins and methods for treating diseases associated with the imbalance or inappropriate activity of hYAK3 proteins.

  这项发明涉及新识别的化合物，用于抑制hYAK3蛋白，并用于治疗与hYAK3蛋白不平衡或不适当活性相关的疾病的方法。
• Substituted Aryloxymethyl Bicyclicmethyl Acetamide Compounds
  申请人：Inoue Tadashi

  公开号：US20060270682A1

  公开（公告）日：2006-11-30

  This invention provides a compound of the formula (I): wherein A=B=D represents NR 10 —C(O)—NR 9 , S—C(O)—NR 9 , NR 9 —C(O)—S, NR 9 —C(O)—O, CR 10 —C(O)—NR 9 , O—C(O)—NR 9 , NR 10 —C(O)—CR 9 , NR 10 —NR 9 —C(O), C(O)—NR 9 —NR 10 , NR 10 —N═CR 9 , N═N—CR 9 , NR 10 —CR 9 ═N, N═CR 9 —NR 10 , NR 10 —N═N, N═N—NR 10 , S—CR 9 ═N or N═CR 9 —S; X 1 represents CR 1 or N; X 2 and X 3 each independently represents CR 8 or N; R 1 , R 6 , R 8 , R 9 and R 10 each independently represents hydrogen, halogen, hydroxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthio, (C 1 -C 6 )alkylsulfinyl or (C 1 -C 6 )alkylsulfonyl; R 2 , R 3 , R 4 , and R 5 each independently represents hydrogen, (C 1 -C 6 )alkyl, halogen, halo(C 1 -C 6 )alkyl, or hydroxy(C 1 -C 6 )alkyl; and R 7 represents halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkoxy, [(C 1 -C 6 )alkyl]NH— or [(C 1 -C 6 )alkyl] 2 N—; or a pharmaceutically acceptable salt thereof, provided that: (i) when A=B=D represents NR 10 —N═N or N═N—NR 10 , then R 2 represents (C 1 -C 6 )alkyl, halogen, halo(C 1 -C 6 )alkyl or hydroxy(C 1 -C 6 )alkyl; or (ii) when A=B=D represents NR 10 —N═N or N═N—NR 10 , and R 2 represents (C 1 -C 6 )alkyl, then R 7 represents halogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, hydroxy(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy-(C 1 -C 6 )alkoxy, [(C 1 -C 6 )alkyl]NH— or [(C 1 -C 6 )alkyl] 2 N—. These compounds are useful for the treatment of disease conditions caused by overactivation of VR1 receptor such of pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.

  本发明提供了式（I）的化合物：其中A = B = D表示NR10-C（O）-NR9，S-C（O）-NR9，NR9-C（O）-S，NR9-C（O）-O，CR10-C（O）-NR9，O-C（O）-NR9，NR10-C（O）-CR9，NR10-NR9-C（O），C（O）-NR9-NR10，NR10-N═CR9，N═N-CR9，NR10-CR9═N，N═CR9-NR10，NR10-N═N，N═N-NR10，S-CR9═N或N═CR9-S; X1表示CR1或N; X2和X3分别独立地表示CR8或N; R1，R6，R8，R9和R10分别独立地表示氢，卤素，羟基，（C1-C6）烷基，（C1-C6）烷氧基，羟基（C1-C6）烷氧基，（C1-C6）烷氧基-（C1-C6）烷基，（C1-C6）烷氧基-（C1-C6）烷氧基，卤代（C1-C6）烷基，（C1-C6）烷基硫醇，（C1-C6）烷基亚砜基或（C1-C6）烷基磺酰基; R2，R3，R4和R5分别表示氢，（C1-C6）烷基，卤素，卤代（C1-C6）烷基或羟基（C1-C6）烷基; R7表示卤素，（C1-C6）烷基，卤代（C1-C6）烷基，（C1-C6）烷氧基，羟基（C1-C6）烷氧基，（C1-C6）烷氧基-（C1-C6）烷基，（C1-C6）烷氧基-（C1-C6）烷氧基，[(C1-C6)烷基]NH-或[(C1-C6)烷基]2N-;或其药学上可接受的盐，前提是：（i）当A = B = D表示NR10-N═N或N═N-NR10时，R2表示（C1-C6）烷基，卤素，卤代（C1-C6）烷基或羟基（C1-C6）烷基;或（ii）当A = B = D表示NR10-N═N或N═N-NR10，并且R2表示（C1-C6）烷基时，R7表示卤素，（C1-C6）烷基，（C1-C6）烷氧基，羟基（C1-C6）烷氧基，（C1-C6）烷氧基-（C1-C6）烷基，（C1-C6）烷氧基-（C1-C6）烷氧基，[(C1-C6)烷基]NH-或[(C1-C6)烷基]2N-。这些化合物对于治疗哺乳动物中由VR1受体过度激活引起的疾病状况，例如疼痛等，具有用途。本发明还提供了包含上述化合物的制药组合物。