3-fluoro-N-methyl-4-nitrobenzamide | 658700-20-0

• 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-fluoro-N-methyl-4-nitrobenzamide
• CAS: 658700-20-0
• 化学式: C₈H₇FN₂O₃
• 分子量: 198.154
• InChiKey: NWCCVNYDXFXGOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 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：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330
• 危险性描述：
  H302,H315,H320,H335
• 储存条件：
  密封于干燥常温环境中

反应信息

• 作为反应物：
  描述：

  3-fluoro-N-methyl-4-nitrobenzamide 在 palladium 10% on activated carbon 、 水 、 甲酸铵 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 potassium carbonate 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 生成 ARN14494
  参考文献：
  名称：

  Inhibition of Serine Palmitoyltransferase by a Small Organic Molecule Promotes Neuronal Survival after Astrocyte Amyloid Beta 1–42 Injury

  摘要：

  Alzheimer's disease (AD) is a slow-progressing disease of the brain characterized by symptoms such as impairment of memory and other cognitive functions. AD is associated with an inflammatory process that involves astrocytes and microglial cells, among other components. Astrocytes are the most abundant type of glial cells in the central nervous system (CNS). They are involved in inducing neuroinflammation. The present study uses astrocyte-neuron cocultures to investigate how ARN14494, a serine palmitoyltransferase (SPT) inhibitor, affects the CNS in terms of anti inflammation and neuroprotection. SPT is the first rate limiting enzyme in the de novo ceramide synthesis pathway. Consistent evidence suggests that ceramide is increased in AD brain patients. After beta-amyloid 1-42 injury in an in vitro model of AD, ARN14494 inhibits SPT activity and the synthesis of long-chain ceramides and dihydroceramides that are involved in AD progression. In mouse primary cortical astrocytes, ARN14494 prevents the synthesis of proinflammatory cytokines TNF alpha and IL1 beta growth factor TGF beta 1, and oxidative stress-related enzymes iNOS and COX2. ARN14494 also exerts neuroprotective properties in primary cortical neurons. ARN14494 decreases neuronal death and caspase-3 activation in neurons, when the neuroinflammation is attenuated in astrocytes. These findings suggest that ARN14494 protects neurons from beta-amyloid 1-42 induced neurotoxicity through a variety of mechanisms, including antioxidation, antiapoptosis, and anti-inflammation. SPT inhibition could therefore be a safe therapeutic strategy for ameliorating the pathology of Alzheimer's disease.

  DOI：

  10.1021/acschemneuro.8b00556
• 作为产物：
  描述：

  3-氟-4-硝基苯甲酸 在 草酰氯 、 三乙胺 作用下， 以 水 为溶剂， 生成 3-fluoro-N-methyl-4-nitrobenzamide
  参考文献：
  名称：

  Inhibition of Serine Palmitoyltransferase by a Small Organic Molecule Promotes Neuronal Survival after Astrocyte Amyloid Beta 1–42 Injury

  摘要：

  Alzheimer's disease (AD) is a slow-progressing disease of the brain characterized by symptoms such as impairment of memory and other cognitive functions. AD is associated with an inflammatory process that involves astrocytes and microglial cells, among other components. Astrocytes are the most abundant type of glial cells in the central nervous system (CNS). They are involved in inducing neuroinflammation. The present study uses astrocyte-neuron cocultures to investigate how ARN14494, a serine palmitoyltransferase (SPT) inhibitor, affects the CNS in terms of anti inflammation and neuroprotection. SPT is the first rate limiting enzyme in the de novo ceramide synthesis pathway. Consistent evidence suggests that ceramide is increased in AD brain patients. After beta-amyloid 1-42 injury in an in vitro model of AD, ARN14494 inhibits SPT activity and the synthesis of long-chain ceramides and dihydroceramides that are involved in AD progression. In mouse primary cortical astrocytes, ARN14494 prevents the synthesis of proinflammatory cytokines TNF alpha and IL1 beta growth factor TGF beta 1, and oxidative stress-related enzymes iNOS and COX2. ARN14494 also exerts neuroprotective properties in primary cortical neurons. ARN14494 decreases neuronal death and caspase-3 activation in neurons, when the neuroinflammation is attenuated in astrocytes. These findings suggest that ARN14494 protects neurons from beta-amyloid 1-42 induced neurotoxicity through a variety of mechanisms, including antioxidation, antiapoptosis, and anti-inflammation. SPT inhibition could therefore be a safe therapeutic strategy for ameliorating the pathology of Alzheimer's disease.

  DOI：

  10.1021/acschemneuro.8b00556

文献信息

• Benzene compounds
  申请人：SUZUKI Nobuyasu

  公开号：US20070105899A1

  公开（公告）日：2007-05-10

  The present invention provides novel benzene compounds presented by the following formulas, and analogs thereof, that exert an ACC activity-inhibiting effect that is effective in the treatment of obesity, hyperlipemia, fatty liver, hyperglycemia, impaired glucose tolerance, diabetes, diabetic complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, and diabetic macroangiopathy, hypertension, arteriosclerosis), hypertension, and arteriosclerosis.

  本发明提供了以下公式所示的新型苯化合物及其类似物，具有ACC活性抑制作用，对肥胖、高脂血症、脂肪肝、高血糖、糖耐量受损、糖尿病、糖尿病并发症（糖尿病周围神经病变、糖尿病肾病、糖尿病视网膜病变和糖尿病大血管病变、高血压、动脉硬化）以及高血压和动脉硬化的治疗有效。
• [EN] SUBSTITUTED BENZIMIDAZOLE COMPOUNDS<br/>[FR] COMPOSES BENZIMIDAZOLE SUBSTITUES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2004014905A1

  公开（公告）日：2004-02-19

  Disclosed are substituted benzimidazole compounds of formula (I) wherein R1, R2, R3, R4 and Xa are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and the pharmaceutical compositions comprising these compounds.

  揭示了一种化学式（I）中的取代苯并咪唑化合物，其中R1、R2、R3、R4和Xa在此处定义。该发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫紊乱和过敏性疾病的疾病和病理状况。还揭示了制备这些化合物的方法以及包含这些化合物的药物组合物。
• 一种芳基并咪唑类衍生物及其用途
  申请人：江苏先声药业有限公司

  公开号：CN113004252B

  公开（公告）日：2023-06-09

  本发明涉及一种芳基并咪唑类衍生物及其用途，其为式(I)化合物或其药学上可接受的盐。本发明保护上述的芳基并咪唑类衍生物在制备用于治疗癌症的药物中的应用。本发明保护上述的芳基并咪唑类衍生物在制备用于治疗EGFR突变导致的疾病的药物中的应用。
• Substituted benzimidazole compounds
  申请人：Bentzien Martin Joerg

  公开号：US20050203158A1

  公开（公告）日：2005-09-15

  Disclosed are substituted benzimidazole compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 and X a are defined herein. The compounds of the invention inhibit Itk kinase and are therefore useful for treating diseases and pathological conditions involving inflammation, immunological disorders and allergic disorders. Also disclosed are processes for preparing these compounds and to pharmaceutical compositions comprising these compounds.

  本发明涉及一种式为(I)的取代苯并咪唑化合物：其中R1、R2、R3、R4和Xa如本文所定义。本发明的化合物抑制Itk激酶，因此可用于治疗涉及炎症、免疫性疾病和过敏性疾病的疾病和病理状态。还公开了制备这些化合物的方法和包含这些化合物的制药组合物。
• Discovery of Highly Potent and BMPR2-Selective Kinase Inhibitors Using DNA-Encoded Chemical Library Screening
  作者：Ram K. Modukuri、Diana Monsivais、Feng Li、Murugesan Palaniappan、Kurt M. Bohren、Zhi Tan、Angela F. Ku、Yong Wang、Chandrashekhar Madasu、Jian-Yuan Li、Suni Tang、Gabriella Miklossy、Stephen S. Palmer、Damian W. Young、Martin M. Matzuk

  DOI：10.1021/acs.jmedchem.2c01886

  日期：2023.2.9

  receptor-specific kinase inhibitors hinders therapeutic options for skeletal defects and cancer as a result of an overactivated BMP signaling pathway. By screening 4.17 billion “unbiased” and “kinase-biased” DNA-encoded chemical library molecules, we identified hits CDD-1115 and CDD-1431, respectively, that were low-nanomolar selective kinase inhibitors of BMPR2. Structure–activity relationship studies addressed

  为患者发现单激酶选择性抑制剂具有挑战性，因为人类基因组编码的 500 多种激酶共享高度保守的催化结构域。迄今为止，尚未报道针对单一转化生长因子 β (TGFβ) 家族跨膜受体激酶（包括骨形态发生蛋白受体 2 型 (BMPR2)）的独特选择性抑制剂。由于 BMP 信号通路过度激活，受体特异性激酶抑制剂的缺乏阻碍了骨骼缺陷和癌症的治疗选择。通过筛选 41.7 亿个“无偏向”和“激酶偏向”DNA 编码化学库分子，我们分别鉴定了命中CDD-1115和CDD-1431，它们是 BMPR2 的低纳摩尔选择性激酶抑制剂。结构-活性关系研究解决了代谢不稳定性和高分子量问题，分别产生了有效的 BMPR2 选择性抑制剂类似物CDD-1281 (IC 50 = 1.2 nM) 和CDD-1653 (IC 50 = 2.8 nM)。我们的工作表明，DNA 编码化学技术 (DEC-Tec) 对于识别新型一流、高效、选择性激酶抑制剂是可靠的。