tert-butyl (4-methyl-5-nitropyridin-2-yl)carbamate | 1062134-46-6

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: tert-butyl (4-methyl-5-nitropyridin-2-yl)carbamate
• 英文别名: tert-butyl N-(4-methyl-5-nitropyridin-2-yl)carbamate
• CAS: 1062134-46-6
• 化学式: C₁₁H₁₅N₃O₄
• 分子量: 253.258
• InChiKey: FUSNDLJLKPSLJG-UHFFFAOYSA-N

物化性质

• 熔点：
  186 °C(Solv: ethyl ether (60-29-7); pentane (109-66-0))
• 沸点：
  338.3±42.0 °C(Predicted)
• 密度：
  1.267±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-methyl-5-nitropyridin-2-yl)carbamate 在 四氢吡咯 、 palladium 10% on activated carbon 、 氢气 、 叔丁基锂 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 正戊烷 为溶剂， -78.0~70.0 ℃ 、4.0 MPa 条件下， 反应 3.0h， 生成 tert-butyl (2-(5-(benzyloxy)benzofuran-2-carbonyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)carbamate
  参考文献：
  名称：

  A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia

  摘要：

  Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clinical trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the co-targeting of other RTKs which are required for normal hematopoiesis. This is observed quite frequently. Therefore, novel drugs are necessary to treat AML effectively and safely. Recently bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. In order to optimize these agents we synthesized novel derivatives of these methanones with various substituents. Methanone 16 and its carbamate derivative 17b inhibit FLT3-ITD at least as potently as the TKi AC220 (quizartinib). Models indicate corresponding interactions of 16 and quizartinib with FLT3. The activity of 16 is accompanied by a high selectivity for FLT3-ITD. (c) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112232
• 作为产物：
  描述：

  2-氨基-4-甲基-5-硝基吡啶 、 二碳酸二叔丁酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 tert-butyl (4-methyl-5-nitropyridin-2-yl)carbamate
  参考文献：
  名称：

  5-取代吡唑并[3,4-c]吡啶衍生物的核磁共振研究

  摘要：

  取代的吡唑并吡啶是磷酸二酯酶和细胞周期蛋白依赖性激酶的有效抑制剂。在本研究中，NMR 用于研究 5-取代的吡唑并[3,4-c]吡啶衍生物的潜在 N1-H 和 N2-H 互变异构现象。通过使用 1H、13C 和 15N 化学位移以及间接 1H13C 和 1H15N 偶联常数，对六种化合物进行了全面表征。1H NMR 光谱是在很宽的温度范围内测量的。所有化合物均显示主要以 N1-H 互变异构形式存在。化学屏蔽和间接自旋-自旋耦合的互补量子化学计算支持得出的结构结论。版权所有 © 2008 John Wiley & Sons, Ltd.

  DOI：

  10.1002/mrc.2226

文献信息

• [EN] SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] COMPOSÉS CYCLOPROPYLE SUBSTITUÉS, COMPOSITIONS CONTENANT DE TELS COMPOSÉS ET PROCÉDÉS DE TRAITEMENT
  申请人：MERCK SHARP & DOHME

  公开号：WO2011019538A1

  公开（公告）日：2011-02-17

  Substituted cyclopropyl compounds of the formula I: are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

  取代的环丙基化合物公式I：被披露为用于治疗或预防2型糖尿病和类似病症的有用物质。药物可接受的盐也包括在内。这些化合物作为G蛋白偶联受体GPR-119的激动剂是有用的。
• [EN] SYNTHESIS, PHARMACOLOGY AND USE OF NEW AND SELECTIVE FMS-LIKE TYROSINE KINASE 3 (FLT3) FLT3 INHIBITORS<br/>[FR] SYNTHÈSE, PHARMACOLOGIE ET UTILISATION DE NOUVEAUX INHIBITEURS SÉLECTIFS DE LA TYROSINE KINASE 3 DE TYPE FMS FLT3 (FLT3)
  申请人：UNIV REGENSBURG

  公开号：WO2019034538A1

  公开（公告）日：2019-02-21

  The present invention relates to small molecule compounds of formula (I) and their use as FLT3 inhibitors for the treatment of various diseases, such as acute myeloid leukemia (AML). The present invention further relates to methods of synthesizing the compounds and methods of treatment.

  本发明涉及式(I)的小分子化合物及其作为FLT3抑制剂用于治疗各种疾病，如急性髓系白血病（AML）。本发明还涉及合成这些化合物的方法和治疗方法。
• Synthesis and Antiviral Activity Evaluation of some Novel Acyclic C-Nucleosides
  作者：Nikolaos Lougiakis、Panagiotis Marakos、Nicole Poul、Jan Balzarini

  DOI：10.1248/cpb.56.775

  日期：——

  The preparation of novel 5-amino or 7-hydroxy substituted pyrazolo[4,3-b]pyridine and pyrazolo[3,4-c]pyridine acyclic C-nucleosides is described. Their synthesis was carried out by condensation of suitably substituted lithiated picolines with 2-benzyloxyethoxymethylchloride followed by pyrazole ring annulation. The compounds were evaluated for their antiviral activity against a wide panel of viruses

  描述了新颖的5-氨基或7-羟基取代的吡唑并[4，3-b]吡啶和吡唑并[3，4-c]吡啶无环C-核苷的制备。它们的合成是通过适当取代的锂甲基吡啶与2-苄氧基乙氧基甲基氯化物的缩合，然后进行吡唑环环化来进行的。评估了这些化合物对多种病毒的抗病毒活性，但发现它们在亚毒性浓度下无活性。
• SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
  申请人：Wood Harold B.

  公开号：US20120142706A1

  公开（公告）日：2012-06-07

  Substituted cyclopropyl compounds of the formula I: are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

  本发明公开了化学式I的取代环丙基化合物，其可用于治疗或预防2型糖尿病和类似疾病。其中也包括药学上可接受的盐。这些化合物可用作G蛋白偶联受体GPR-119的激动剂。
• Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment
  申请人：Wood Harold B.

  公开号：US08552022B2

  公开（公告）日：2013-10-08

  Substituted cyclopropyl compounds of the formula I: are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

  公开了式I的替代环丙基化合物，作为治疗或预防2型糖尿病和类似疾病的有用药物。还包括药学上可接受的盐。这些化合物作为G蛋白偶联受体GPR-119的激动剂是有用的。