6-(4-bromophenyl)-2-methylnicotinohydrazide

• 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: 6-(4-bromophenyl)-2-methylnicotinohydrazide
• 英文别名: 6-(4-Bromophenyl)-2-methylpyridine-3-carbohydrazide
• 化学式: C₁₃H₁₂BrN₃O
• 分子量: 306.162
• InChiKey: CVOFCRFWHGUTFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-bromophenyl)-2-methylnicotinohydrazide 在 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 0.25h， 生成 2-({5-[6-(4-bromophenyl)-2-methylpyridin-3-yl]-1,3,4-oxadiazol-2-yl}thio)-1-(p-tolyl)ethan-1-one
  参考文献：
  名称：

  新型基于芳基吡啶的1,3,4-恶二唑：合成，抗菌和抗炎评估

  摘要：

  鉴于开发新型生物活性化合物，一系列2-（5- [2-甲基-6-芳基吡啶3-3-基] -1,3,4-恶二唑-2-基硫基）-1-芳酮（6a–n ）的设计和合成，收率很高。对新型化合物的抗菌和抗炎活性进行了评估。筛选所有合成的化合物对金黄色葡萄球菌，枯草芽孢杆菌，大肠埃希氏菌和铜绿假单胞菌菌株的抗菌活性。化合物6a，6b，6c，6h和6i与标准环丙沙星相比，它具有最高的抗菌活性，最小抑菌浓度（MIC）值在6.25–12.5μg/ mL之间。角叉菜胶诱发的足垫浮肿测定的抗炎活性结果表明，受试化合物在3小时后表现出显着的抗炎活性，抑制百分比为63.9–70.1％（消炎痛活性的96.8–106.20％）。特别是，发现6c – e和6j – l是出色的炎症抑制剂，其潜力比标准消炎痛高。

  DOI：

  10.1002/jccs.201800248
• 作为产物：
  描述：

  1-(4-bromophenyl)-3-(dimethylamino)prop-2-en-1-one 在 ammonium acetate 、 一水合肼 作用下， 以 溶剂黄146 为溶剂， 反应 8.0h， 生成 6-(4-bromophenyl)-2-methylnicotinohydrazide
  参考文献：
  名称：

  Design, Synthesis and Antitubercular Activity of Certain Nicotinic Acid Hydrazides

  摘要：

  合成了三系列6-芳基-2-甲基烟碱酰肼4a–i、N'-芳亚甲基-6-(4-溴苯基)-2-甲基烟碱酰肼7a–f和N'-(未/取代的2-氧代吲哚啉-3-亚甲基)-6-(4-氟苯基)-2-甲基烟碱酰肼8a–c，并评估了它们对结核杆菌的体外抗菌活性。结果显示，靛红酰肼8a–c相较于母体酰肼4c活性显著更高。酰肼8b和8c在所有测试化合物中显示出最高的活性（MIC分别为12.5和6.25 µg/mL）。化合物8b和8c对HT-29、PC-3、A549、HepG2和MCF-7癌细胞系也无明显细胞毒性。此外，8b和8c显示出良好的类药性得分，分别为0.62和0.41。这两个靛红酰肼为未来开发更强效的抗结核药物提供了极佳的基础。SAR研究表明，合成衍生物的亲脂性是影响其抗结核活性的关键因素。最后，建立了理论动力学研究来预测活性衍生物的ADME。

  DOI：

  10.3390/molecules20058800

文献信息

• Novel 6-Phenylnicotinohydrazide Derivatives: Design, Synthesis and Biological Evaluation as a Novel Class of Antitubercular and Antimicrobial Agents
  作者：Dalia Hussein Soliman、Wagdy Mohamed Eldehna、Hazem Ahmed Ghabbour、Maha Mamdouh Kabil、Marwa Mostafa Abdel-Aziz、Hatem Abdel-Kader Abdel-Aziz

  DOI：10.1248/bpb.b17-00361

  日期：——

  In our ongoing efforts to develop potent antitubercular agents based on the 6-phenylnicotinohydrazide, herein we report the design, synthesis and biological evaluation of three sets of 6-phenylnicotinohydrazide derivatives 8a–g, 12 and 16a, b. The designed compounds were synthesized and in vitro evaluated for their antitubercular activity. In addition, their antifungal and antibacterial activities were evaluated as well. The nicotinohydrazide class displayed different levels of antimicrobial activity and possessed a distinctive pattern of selectivity against the tested microorganisms. However, the 2,6-dichlorobenzylidene counterpart 8b emerged as the most active one in this study, with superior antimycobacterial activity (minimum inhibitory concentration (MIC)=3.90 µg/mL) and potent broad-spectrum antimicrobial activities with MIC range of 0.24–1.95 µg/mL. The structure–activity relationship for such nicotinohydrazides has been established. Further, the cytotoxicity of the most active antitubercular compounds 8b, d and g were tested against the normal breast cells WI-38; none of them displayed significant cytotoxic effect, thereby providing a good therapeutic index.

  在我们不断努力开发基于6-苯基烟酰肼的强效抗结核药物的过程中，本文报道了三组6-苯基烟酰肼衍生物8a–g、12和16a,b的设计、合成及生物学评价。所设计的化合物被合成，并在体外评估了它们的抗结核活性。此外，还评估了它们的抗真菌和抗细菌活性。烟酰肼类显示出不同程度的抗微生物活性，并对测试的微生物具有独特的选择性模式。然而，2,6-二氯苯亚甲基衍生物8b在本研究中表现出最强的活性，具有优异的抗分枝杆菌活性（最低抑制浓度(MIC)=3.90µg/mL）和强效的广谱抗微生物活性，MIC范围为0.24-1.95µg/mL。建立了这类烟酰肼的构效关系。进一步地，对活性最强的抗结核化合物8b、d和g进行了正常乳腺细胞WI-38的细胞毒性测试；它们均未显示出显著的细胞毒性效应，从而提供了良好的治疗指数。
• Design, Synthesis and Antitubercular Activity of Certain Nicotinic Acid Hydrazides
  作者：Wagdy Eldehna、Mohamed Fares、Marwa Abdel-Aziz、Hatem Abdel-Aziz

  DOI：10.3390/molecules20058800

  日期：——

  Three series of 6-aryl-2-methylnicotinohydrazides 4a–i, N′-arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a–f, and N′-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a–c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M. tuberculosis. The results showed that isatin hydrazides 8a–c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 µg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.

  合成了三系列6-芳基-2-甲基烟碱酰肼4a–i、N'-芳亚甲基-6-(4-溴苯基)-2-甲基烟碱酰肼7a–f和N'-(未/取代的2-氧代吲哚啉-3-亚甲基)-6-(4-氟苯基)-2-甲基烟碱酰肼8a–c，并评估了它们对结核杆菌的体外抗菌活性。结果显示，靛红酰肼8a–c相较于母体酰肼4c活性显著更高。酰肼8b和8c在所有测试化合物中显示出最高的活性（MIC分别为12.5和6.25 µg/mL）。化合物8b和8c对HT-29、PC-3、A549、HepG2和MCF-7癌细胞系也无明显细胞毒性。此外，8b和8c显示出良好的类药性得分，分别为0.62和0.41。这两个靛红酰肼为未来开发更强效的抗结核药物提供了极佳的基础。SAR研究表明，合成衍生物的亲脂性是影响其抗结核活性的关键因素。最后，建立了理论动力学研究来预测活性衍生物的ADME。
• Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase
  作者：Chang-bo Deng、Juan Li、Lu-yi Li、Feng-jie Sun

  DOI：10.1016/j.bmcl.2016.04.031

  日期：2016.7

  In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 +/- 2.5 mu M). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury. (C) 2016 Elsevier Ltd. All rights reserved.
• Novel arylpyridine‐based 1,3,4‐oxadiazoles: Synthesis, antibacterial, and anti‐inflammatory evaluation
  作者：Sowmya Padejjar Vasantha、Boja Poojary、Revanasiddappa Bistuvalli Chandrashekarappa

  DOI：10.1002/jccs.201800248

  日期：2019.6

  developing novel bioactive compounds, a series of 2‐(5‐[2‐methyl‐6‐arylpyridin‐3‐yl]‐1,3,4‐oxadiazol‐2‐ylthio)‐1‐arylethanones (6a–n) were designed and synthesized in good yield. Novel compounds were evaluated for their antibacterial and anti‐inflammatory activities. All synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bascillus subtilis, Eschericia coli,

  鉴于开发新型生物活性化合物，一系列2-（5- [2-甲基-6-芳基吡啶3-3-基] -1,3,4-恶二唑-2-基硫基）-1-芳酮（6a–n ）的设计和合成，收率很高。对新型化合物的抗菌和抗炎活性进行了评估。筛选所有合成的化合物对金黄色葡萄球菌，枯草芽孢杆菌，大肠埃希氏菌和铜绿假单胞菌菌株的抗菌活性。化合物6a，6b，6c，6h和6i与标准环丙沙星相比，它具有最高的抗菌活性，最小抑菌浓度（MIC）值在6.25–12.5μg/ mL之间。角叉菜胶诱发的足垫浮肿测定的抗炎活性结果表明，受试化合物在3小时后表现出显着的抗炎活性，抑制百分比为63.9–70.1％（消炎痛活性的96.8–106.20％）。特别是，发现6c – e和6j – l是出色的炎症抑制剂，其潜力比标准消炎痛高。
• Novel 1,3,5‐triazine‐nicotinohydrazide derivatives induce cell arrest and apoptosis in osteosarcoma cancer cells and inhibit osteosarcoma in a patient‐derived orthotopic xenograft mouse model
  作者：Qing Su、Baolin Xu、Zhoubin Tian、Ziling Gong

  DOI：10.1111/cbdd.13986

  日期：2022.2

  AbstractThe present study deals with developing novel 1,3,5‐triazine‐nicotinohydrazide derivatives as potent CDK9 inhibitors in a straightforward synthetic route with potent anti‐osteosarcoma activity. The most potent CDK9 inhibitor compound 5k inhibits proliferation of MG‐63 cells via induction of apoptosis and G2/M cell cycle arrest. It reduces tumor progression in the patient‐derived orthotopic xenograft (PDOX) mouse model with significant antioxidant and anti‐inflammatory activity. In tumor tissue homogenates, it caused significant inhibition of CDK9 and inhibited the phosphorylation of RNAPII ser2 and reduced MCL‐1 expression in Western blot analysis. Compound 5k also showed considerable bioavailability in SD mice. Our results demonstrated that compound 5k inhibits growth of OS in vitro and in vivo via inhibition of CDK9 which attenuated the downstream phosphorylation of RNAPII ser2 and represses expression of the anti‐apoptotic protein, MCL‐1 for the induction of apoptosis in OS.