4-nitrophenyl (5-(tert-butyl)isoxazol-3-yl)carbamate | 685533-79-3

• 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: 4-nitrophenyl (5-(tert-butyl)isoxazol-3-yl)carbamate
• 英文别名: (5-t-butyl-3-isoxazolyl)carbamic acid 4-nitrophenyl ester；4-Nitrophenyl N-[5-(1,1-dimethylethyl)-3-isoxazolyl]carbamate；(4-nitrophenyl) N-(5-tert-butyl-1,2-oxazol-3-yl)carbamate
• CAS: 685533-79-3
• 化学式: C₁₄H₁₅N₃O₅
• 分子量: 305.29
• InChiKey: ACVATSRJIDQPTH-UHFFFAOYSA-N

物化性质

• 沸点：
  440.2±45.0 °C(Predicted)
• 密度：
  1.333±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-nitrophenyl (5-(tert-butyl)isoxazol-3-yl)carbamate 、 C₁₉H₂₃N₇S 在 吡啶 作用下， 反应 2.0h， 生成 N-[5-(tert-butyl)-3-isoxazolyl]-N'-[4-(2-[2-methyl-6-(4-methylpiperazino)-4-pyrimidinyl]amino-1,3-thiazol-4-yl)phenyl]urea
  参考文献：
  名称：

  Identification of a potent 5-phenyl-thiazol-2-ylamine-based inhibitor of FLT3 with activity against drug resistance-conferring point mutations

  摘要：

  Numerous FLT3 inhibitors have been explored as a viable therapy for the treatment of acute myeloid leukemia (AML). However, clinical data have been underwhelming due to incomplete inhibition of FLT3 or the emergence of resistant mutations treated with these older agents. We previously developed a series of 3-phenyl-1H-5-pyrazolylamine derivatives as highly potent and selective FLT3 inhibitors with good in vivo efficacy using an intravenous (IV) route. However, the poor bioavailability of these pyrazole compounds limits the development of these promising antileukemic compounds for clinical use. Herein, we describe a novel class of 5-phenyl-thiazol-2-ylamine compounds that are multi-targeted FLT3 inhibitors. From this class of compounds, compound 7h was very potent against AML cell lines and exhibited excellent oral efficacy in AML xenograft models. In addition, further studies demonstrated that compound 7h exhibited potent in vitro and in vivo activities against clinically relevant AC220 (3)-resistant kinase domain mutants of FLT3-ITD. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.05.008
• 作为产物：
  描述：

  3-氨基-5-叔丁基异唑 、 对硝基苯基氯甲酸酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以90%的产率得到4-nitrophenyl (5-(tert-butyl)isoxazol-3-yl)carbamate
  参考文献：
  名称：

  [EN] METHYLENE UREA DERIVATIVES AS RAF-KINASE INHIBITORS
  [FR] DERIVES DE METHYLENE UREE

  摘要：

  公开号：

  WO2004037789A3

文献信息

• NOVEL IMIDAZOPYRIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT FOR PREVENTING OR TREATING CANCER
  申请人：DAEGU-GYEONGBUK MEDICAL INNOVATION FOUNDATION

  公开号：US20190315738A1

  公开（公告）日：2019-10-17

  The present invention relates to a novel imidazopyridine derivative, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating cancer. The novel imidazopyridine derivative according to the present invention, a stereoisomer thereof and a pharmaceutically acceptable salt thereof can effectively inhibit cancer-related kinases, are excellent in inhibiting proliferation of cancer cells in a cancer cell line, and effectively inhibit proliferation of cancer cells (cancer cell apoptosis) in a cancer cell heterograft model, and thus can be useful as a pharmaceutical composition containing the same as an active ingredient for preventing or treating cancer. Also, the novel imidazopyridine derivative according to the present invention, the stereoisomer thereof, and the pharmaceutically acceptable salt thereof can effectively inhibit Src and Fyn, thereby being useful as a pharmaceutical composition for preventing or treating the Src and Fyn related diseases, and in particular, have been confirmed to be useful in diabetic nephropathy in animal model experiments. Therefore, the compound of the present invention can be effective as a pharmaceutical composition containing the same as an active ingredient for preventing or treating diabetic nephropathy.

  本发明涉及一种新的咪唑吡啶衍生物，一种制备该衍生物的方法，以及含有该衍生物作为活性成分用于预防或治疗癌症的药物组合物。根据本发明的新的咪唑吡啶衍生物及其立体异构体和药学上可接受的盐可以有效抑制与癌症相关的激酶，在癌细胞系中抑制癌细胞增殖方面表现出优异，有效抑制癌细胞在癌细胞异种移植模型中的增殖（癌细胞凋亡），因此可以作为含有该衍生物作为活性成分的药物组合物用于预防或治疗癌症。此外，根据本发明的新的咪唑吡啶衍生物、其立体异构体和药学上可接受的盐可以有效抑制Src和Fyn，因此可用作预防或治疗与Src和Fyn相关疾病的药物组合物，特别在动物模型实验中已确认在糖尿病肾病中有用。因此，本发明的化合物可以作为含有该衍生物作为活性成分的药物组合物，有效预防或治疗糖尿病肾病。
• Pyrazolylamine Derivatives Reveal the Conformational Switching between Type I and Type II Binding Modes of Anaplastic Lymphoma Kinase (ALK)
  作者：Chih-Hsiang Tu、Wen-Hsing Lin、Yi-Hui Peng、Tsu Hsu、Jian-Sung Wu、Chun-Yu Chang、Cheng-Tai Lu、Ping-Chiang Lyu、Chuan Shih、Weir-Torn Jiaang、Su-Ying Wu

  DOI：10.1021/acs.jmedchem.6b00106

  日期：2016.4.28

  anaplastic lymphoma kinase (ALK) inhibitors adopt a type I binding mode, but only limited type II ALK structural studies are available. Herein, we present the structure of ALK in complex with N1-(3-4-[([5-(tert-butyl)-3-isoxazolyl]aminocarbonyl)amino]-3-methylphenyl-1H-5-pyrazolyl)-4-[(4-methylpiperazino)methyl]benzamide (5a), a novel ALK inhibitor adopting a type II binding mode. It revealed binding

  大多数变性间变性淋巴瘤激酶（ALK）抑制剂采用I型结合模式，但仅有有限的II型ALK结构研究可用。在这里，我们介绍了与N 1-（3-4-[（[[（5-（叔丁基）-3-异恶唑基]氨基羰基）氨基] -3-甲基苯基-1 H -5-吡唑基）形成的ALK的结构。-4-[（4-甲基哌嗪子基）甲基]苯甲酰胺（5a），一种新型的ALK抑制剂，采用II型结合模式。揭示了5a的结合导致激活环，αC-螺旋和近膜结构域的构象变化和重新定位，它们都是ALK的自抑制机制和下游信号通路调控的重要结构域。结构-活性关系研究表明，对5a结构的修饰导致ALK效能显着不同，并改变了ALK的蛋白质结构。据我们所知，这是第一个直接观察小分子结构变化如何调节I型和II型结合模式之间的转换并诱导剧烈构象变化的结构生物学研究。
• Methylene urea derivative as RAF kinasse inhibitors
  申请人：Merck Patent GmbH

  公开号：EP2426122A1

  公开（公告）日：2012-03-07

  The present invention relates to methylene urea derivatives of formula I, the use of the compounds of formula I as inhibitors of raf-kinase, the use of the compounds of formula I for the manufacture of a pharmaceutical composition and a method of treatment, comprising administering said pharmaceutical composition to a patient.

  本发明涉及式 I 的亚甲基脲衍生物、式 I 化合物作为雷夫激酶抑制剂的用途、式 I 化合物用于制造药物组合物的用途以及治疗方法，包括将所述药物组合物施用给患者。
• Imidazopyridine derivative, method for preparing same, and pharmaceutical composition containing same as active ingredient for preventing or treating cancer
  申请人：DAEGU-GYEONGBUK MEDICAL INNOVATION FOUNDATION

  公开号：US10870647B2

  公开（公告）日：2020-12-22

  The present invention relates to a novel imidazopyridine derivative, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating cancer. The novel imidazopyridine derivative according to the present invention, a stereoisomer thereof and a pharmaceutically acceptable salt thereof can effectively inhibit cancer-related kinases, are excellent in inhibiting proliferation of cancer cells in a cancer cell line, and effectively inhibit proliferation of cancer cells (cancer cell apoptosis) in a cancer cell heterograft model, and thus can be useful as a pharmaceutical composition containing the same as an active ingredient for preventing or treating cancer. Also, the novel imidazopyridine derivative according to the present invention, the stereoisomer thereof, and the pharmaceutically acceptable salt thereof can effectively inhibit Src and Fyn, thereby being useful as a pharmaceutical composition for preventing or treating the Src and Fyn related diseases, and in particular, have been confirmed to be useful in diabetic nephropathy in animal model experiments. Therefore, the compound of the present invention can be effective as a pharmaceutical composition containing the same as an active ingredient for preventing or treating diabetic nephropathy.

  本发明涉及一种新型咪唑吡啶衍生物、其制备方法以及一种含有该衍生物作为有效成分的预防或治疗癌症的药物组合物。根据本发明的新型咪唑吡啶衍生物、其立体异构体和其药学上可接受的盐可有效抑制癌症相关激酶，在抑制癌细胞系中的癌细胞增殖方面表现出色，并可有效抑制癌细胞异种移植模型中的癌细胞增殖（癌细胞凋亡），因此可作为含有其作为活性成分的药物组合物用于预防或治疗癌症。 另外，根据本发明的新型咪唑吡啶衍生物、其立体异构体及其药学上可接受的盐可以有效抑制 Src 和 Fyn，从而可作为药物组合物用于预防或治疗与 Src 和 Fyn 相关的疾病，特别是已在动物模型实验中证实可用于糖尿病肾病。因此，本发明的化合物作为一种含有相同活性成分的药物组合物，可有效预防或治疗糖尿病肾病。
• METHYLENE UREA DERIVATIVES
  申请人：Buchstaller Hans-Peter

  公开号：US20090298885A1

  公开（公告）日：2009-12-03

  The present invention relates to methylene urea derivatives of formula (I), the use of the compounds of formula (I) as inhibitors of raf-kinase, the use of the compounds of formula (I) for the manufacture of a pharmaceutical composition and a method of treatment, comprising administering said pharmaceutical composition to a patient.