异噁唑-5-甲胺 | 401647-18-5

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 异噁唑-5-甲胺
• 中文别名: 5-氨甲基异噁唑；C-异恶唑-5-甲胺；异恶唑-5-基甲胺
• 英文名称: isoxazol-5-ylmethanamine
• 英文别名: 5-(aminomethyl)isoxazole；1,2-oxazol-5-ylmethanamine
• CAS: 401647-18-5
• 化学式: C₄H₆N₂O
• mdl: MFCD06738818
• 分子量: 98.1044
• InChiKey: OYNWFDBANWIYDA-UHFFFAOYSA-N

物化性质

• 沸点：
  207.0±15.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  异噁唑-5-甲胺 、 以 二氯甲烷 为溶剂， 生成 2,4-dimethylpentan-3-yl N-[(3S)-1-(1,2-oxazol-5-ylmethylamino)-1,2-dioxoheptan-3-yl]carbamate
  参考文献：
  名称：

  Orally bioavailable small molecule ketoamide-based inhibitors of cathepsin K

  摘要：

  An orally available series of ketoamide-based inhibitors of cathepsin K has been identified. Starting from a potent inhibitor with poor oral bioavailability, modifications to P-1 and P-1' elements led to enhancements in solubility and permeability. These improvements resulted in orally available cathepsin K inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.085
• 作为产物：
  描述：

  5-Azidomethyl-isoxazole 在 水 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以77%的产率得到异噁唑-5-甲胺
  参考文献：
  名称：

  基于BnIm和Radamide支架的葡萄糖调节蛋白94选择性抑制剂的开发。

  摘要：

  葡萄糖调节蛋白94（Grp94）是分子伴侣蛋白的热休克蛋白90 kDa（Hsp90）家族的内质网居民。Grp94与许多参与细胞黏附和信号传导的蛋白质相关，包括整联蛋白，Toll样受体，免疫球蛋白和突变型myocilin。Grp94被认为是包括青光眼，癌症转移和多发性骨髓瘤在内的多个治疗领域的靶标。虽然与其他Hsp90同工型具有85％的相同性，但Grp94的N末端ATP结合位点具有一个独特的疏水性口袋，该口袋用于设计同工型选择性抑制剂。合并顺式-酰胺生物甾体进入radamide支架导致了最初的Grp94选择性抑制剂BnIm的开发。现在已经对BnIm的芳基侧链进行了结构-活性关系研究，从而得到了改进的类似物，对Grp94表现出了更好的效价和选择性。与BnIm相比，这些类似物在转移模型中还表现出优异的抗迁移活性，并且在青光眼模型中还表现出增强的突变型肌球蛋白降解。

  DOI：

  10.1021/acs.jmedchem.6b00085

文献信息

• [EN] 5-SULFAMOYL-2-HYDROXYBENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE 5-SULFAMOYL-2-HYDROXYBENZAMIDE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017153952A1

  公开（公告）日：2017-09-14

  The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代水杨酰胺衍生物。具体而言，本发明涉及根据公式(I)的化合物：其中R、R1和R2如本文所述，或其药用可接受的盐。本发明的化合物是CD73的抑制剂，可用于治疗癌症、前癌症综合症以及与CD73抑制相关的疾病，例如艾滋病、治疗HIV、自身免疫疾病、感染、动脉粥样硬化和缺血再灌注损伤。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制CD73活性和治疗与之相关的疾病的方法。
• Tetrahydroisoquinolines as Orexin Receptor Antagonists: Strategies for Lead Optimization by Solution-Phase Chemistry
  作者：Ralf Koberstein、Alexander Treiber、Thierry Sifferlen、Oliver Nayler、Celia Mueller、François Jenck、Walter Fischli、Martine Clozel、Daniel Bur、Hamed Aissaoui、Thomas Weller

  DOI：10.2533/000942903777679361

  日期：——

  Different techniques can be applied for the automated production of small and large compound collections. Large libraries that are often generated and tested during the lead-finding stage of a project are typically produced by solid-phase chemistry. Libraries that are significantly smaller in size are often synthesized in solution. Chemistry in solution is rather versatile, offers numerous advantages and is therefore often the method of choice for generating small libraries during a lead optimization process. Fast and reliable purification procedures are required to yield compounds of high quality that can be immediately used in biological as well as pharmacological assays. Solution-phase chemistry combined with automated purification was applied to optimize initial lead inhibitors for the two human orexin receptors OX1 and OX2. Starting from a submicro-molar OX1 selective lead compound, low nanomolar analogues with improved physico-chemical properties were synthesized that antagonize either one or both orexin receptors.

  不同的技术可以应用于自动生产小型和大型化合物集合。通常在项目的引导发现阶段生成和测试的大型文库通常由固相化学产生。大小明显较小的文库通常在溶液中合成。溶液中的化学反应非常灵活，具有许多优势，因此通常是在引导优化过程中生成小型文库的首选方法。需要快速可靠的纯化程序，以产生高质量的化合物，可以立即用于生物学和药理学实验。将溶液相化学与自动纯化相结合，用于优化两种人类促觉素受体OX1和OX2的初始引导抑制剂。从次微摩尔的OX1选择性引导化合物开始，合成了具有改进的物理化学性质的低纳摩尔类似物，这些类似物拮抗了促觉素受体中的一个或两个。
• P2–P3 conformationally constrained ketoamide-based inhibitors of cathepsin K
  作者：David G. Barrett、Virginia M. Boncek、John G. Catalano、David N. Deaton、Anne M. Hassell、Cynthia H. Jurgensen、Stacey T. Long、Robert B. McFadyen、Aaron B. Miller、Larry R. Miller、J. Alan Payne、John A. Ray、Vicente Samano、Lisa M. Shewchuk、Francis X. Tavares、Kevin J. Wells-Knecht、Derril H. Willard、Lois L. Wright、Hui-Qiang Q. Zhou

  DOI：10.1016/j.bmcl.2005.05.062

  日期：2005.8

  An orally bioavailable series of ketoamide-based cathepsin K inhibitors with good pharmacokinetic properties has been identified. Starting from a potent inhibitor endowed with poor drug properties, conformational constraint of the P(2)-P(3) linker and modifications to P(1') elements led to an enhancement in potency, solubility, clearance, and bioavailability. These optimized inhibitors attenuated bone resorption in a rat TPTX hypocalcemic bone resorption model.
• Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy
  作者：Ying Huang、Jeff Zhang、Zhengtian Yu、Hailong Zhang、Youzhen Wang、Andreas Lingel、Wei Qi、Justin Gu、Kehao Zhao、Michael D. Shultz、Long Wang、Xingnian Fu、Yongfeng Sun、Qiong Zhang、Xiangqing Jiang、Jiangwei Zhang、Chunye Zhang、Ling Li、Jue Zeng、Lijian Feng、Chao Zhang、Yueqin Liu、Man Zhang、Lijun Zhang、Mengxi Zhao、Zhenting Gao、Xianghui Liu、Douglas Fang、Haibing Guo、Yuan Mi、Tobias Gabriel、Michael P. Dillon、Peter Atadja、Counde Oyang

  DOI：10.1021/acs.jmedchem.6b01576

  日期：2017.3.23

  Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2(MUT) preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.
• Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABA_A Receptor Negative Allosteric Modulators
  作者：György Szabó、Olivér Éliás、Péter Erdélyi、Attila Potor、György I. Túrós、Benedek I. Károlyi、Gábor Varró、Ágnes Gy. Vaskó、Imre Bata、Gábor L. Kapus、Zoltán Dohányos、Amrita Á. Bobok、László Fodor、Márta Thán、Mónika Vastag、Zsolt Komlódi、Rita É. Soukupné Kedves、Éva Makó、Brigitta Süveges、István Greiner

  DOI：10.1021/acs.jmedchem.2c00414

  日期：2022.6.9