N-methyl-2-(p-tolyl)acetamide | 98245-60-4

• 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: N-methyl-2-(p-tolyl)acetamide
• 英文别名: N-methyl-2-(4-methylphenyl)acetamide
• CAS: 98245-60-4
• 化学式: C₁₀H₁₃NO
• mdl: MFCD03033750
• 分子量: 163.219
• InChiKey: XVBDNKODNGFLTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-methyl-2-(p-tolyl)acetamide 在 2,4,6-三甲基吡啶 、 1H-咪唑-1-磺酰叠氮 、 硼烷四氢呋喃络合物 、 bis{rhodium[3,3'-(1,3-phenylene)bis(2,2-dimethylpropanoic acid)]} 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 28.0h， 生成 C₁₃H₁₄N₂O
  参考文献：
  名称：

  α-Diazo-β-ketonitriles: Uniquely Reactive Substrates for Arene and Alkene Cyclopropanation

  摘要：

  An investigation of the intramolecular cyclopropanation reactions of alpha-diazo-beta-ketonitriles is reported. These studies reveal that alpha-diazo-beta-ketonitriles exhibit unique reactivity in their ability to undergo arene cyclopropanation reactions; other similar acceptor acceptor-substituted diazo substrates instead produce mixtures of C-H insertion and dimerization products. alpha-Diazo-beta-ketonitriles also undergo highly efficient intramolecular cyclopropanation of tri- and tetrasubstituted alkenes. In addition, the alpha-cyano-alpha-ketocyclopropane products are demonstrated to serve as substrates for S(N)2, S(N)2', and aldehyde cycloaddition reactions.

  DOI：

  10.1021/ja401610p
• 作为产物：
  描述：

  对甲基苯乙酸 在 草酰氯 、 碳酸氢钠 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 19.0h， 生成 N-methyl-2-(p-tolyl)acetamide
  参考文献：
  名称：

  Copper‐Catalyzed C−H (Phenylsulfonyl)difluoromethylation of Acrylamides: Scope, Mechanism, and Critical Role of Additives

  摘要：

  摘要我们在此报告了铜络合物催化、原生官能团辅助和 TFA/NMF 添加剂促进的丙烯酰胺乙烯基 C(sp2)-H键（苯磺酰基）二氟甲基化反应。利用我们自行设计的试剂，该反应可在温和的反应条件下，通过铜催化从简单的 C-H 键活化生成 C(sp2)-CF2SO2Ph 键，并具有完全的 Z 选择性。利用氟化基团将其转化为高附加值的 CF2 分子以及显著的 =CHF 残基，说明了氟化基团的多功能性。通过实验和计算机理研究，确定了活性催化剂和底物的真正性质，并确定了反式脂肪酸和 NMF 添加剂的关键作用。在这一反应中，反式脂肪酸对急需的 CuII/CuII→CuIII/CuI 歧化起到了促进作用，而 NMF 则促进了接下来的配体交换和 C-C 偶联过程。我们排除了自由基中间产物的产生，并确定 C-H 活化是不可逆的，而且是整个过程的速率决定步骤。

  DOI：

  10.1002/chem.202303362

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20190151295A1

  公开（公告）日：2019-05-23

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为白细胞介素-1受体相关激酶4（IRAK-4；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合E3泛素连接酶的Von Hppel-Lindau、cereblon配体的双功能化合物，另一端结合目标蛋白的部分，使得目标蛋白靠近泛素连接酶以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。
• Derivatives Of Pentose Monosaccharides As Anti-Inflammatory Compounds
  申请人：Sattigeri Viswajanani Jitendra

  公开号：US20090075909A1

  公开（公告）日：2009-03-19

  The present invention relates to monosaccharide derivatives as anti-inflammatory agents. The compounds of this invention can be useful for inhibition and prevention of inflammation and associated pathologies, including inflammatory and autoimmune diseases, for example, bronchial asthma, rheumatoid arthritis, type I diabetes, multiple sclerosis, allograft rejection or psoriasis. The present invention also relates to pharmacological compositions containing these monosaccharide derivatives, as well as methods of treating bronchial asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple sclerosis, type I diabetes, psoriasis, allograft rejection, and other inflammatory and/or auto immune disorders.

  本发明涉及单糖衍生物作为抗炎药剂。本发明的化合物可用于抑制和预防炎症及相关病理，包括炎症性和自身免疫性疾病，例如支气管哮喘、类风湿关节炎、I 型糖尿病、多发性硬化症、移植排斥或牛皮癣。本发明还涉及含有这些单糖衍生物的药物组合物，以及治疗支气管哮喘、慢性阻塞性肺病、类风湿关节炎、多发性硬化症、I 型糖尿病、牛皮癣、移植排斥和其他炎症和/或自身免疫性疾病的方法。
• Growth Hormone Conjugate with Increased Stability
  申请人：Johansen Nils Langeland

  公开号：US20110263501A1

  公开（公告）日：2011-10-27

  Novel growth hormone conjugates comprising a growth hormone compound (GH) and a growth hormone binding protein (GHBP) are disclosed. The invention also encompasses a novel derivatization method for producing stable, long-lasting conjugate (hGH-GHBP) by site specific conjugation. The novel GH-GHBP conjugates have an extended half-life in circulation that facilitates therapeutic use of the protein. The GH-GHBP conjugates exhibit pharmacological properties such as increased functional in vivo half-life, improved renal filtration, improved protease protection and albumin binding.

  揭示了包括生长激素化合物（GH）和生长激素结合蛋白（GHBP）的新型生长激素共轭物。该发明还涵盖了一种用于通过位点特异性结合制备稳定、持久的共轭物（hGH-GHBP）的新型衍生化方法。新型GH-GHBP共轭物在循环中具有延长的半衰期，有助于蛋白质的治疗应用。GH-GHBP共轭物表现出诸如增加的体内功能半衰期、改善的肾脏过滤、改善的蛋白酶保护和结合白蛋白等药理特性。
• C-Terminally Pegylated Growth Hormones
  申请人：Zundel Magali

  公开号：US20090105134A1

  公开（公告）日：2009-04-23

  Conjugated growth hormones of the structure (I) are provided together with methods for manufacturing said conjugates. The conjugates are useful in therapy.

  提供具有结构（I）的共轭生长激素以及制造所述共轭物的方法。这些共轭物在治疗中很有用。
• CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
  申请人：Arvinas, Inc.

  公开号：US20180215731A1

  公开（公告）日：2018-08-02

  The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。