3β-azido-5-cholestene | 1433-82-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3β-azido-5-cholestene
• 英文别名: 3beta-Azido-5-cholestene；(3S,8S,9S,10R,13R,14S,17R)-3-azido-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene
• CAS: 1433-82-5
• 化学式: C₂₇H₄₅N₃
• 分子量: 411.674
• InChiKey: AHNXVAQNMFHKPJ-DPAQBDIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  14.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3β-azido-5-cholestene 在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 4.0h， 生成 N-cholesteryl-2-nitrobenzenesulfonamide
  参考文献：
  名称：

  Synthetic Mimics of Small Mammalian Cell Surface Receptors

  摘要：

  Receptors on the surface of mammalian cells promote the uptake of cell-impermeable ligands by receptor-mediated endocytosis. To mimic this process, we synthesized small molecules designed to project anti-dinitrophenyl antibody-binding motifs from the surface of living Jurkat lymphocytes. These synthetic receptors comprise N-alkyl derivatives of 3beta-cholesterylamine as the plasma membrane anchor linked to 2,4-dinitrophenyl (DNP) and structurally similar fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) headgroups. Insertion of two beta-alanine subunits between a DNP derivative and 3beta-cholesterylamine yielded a receptor that avidly associates with cell surfaces (cellular t(1/2) similar to 20 h). When added to Jurkat cells at 10 muM, this receptor enhanced uptake of an anti-DNP IgG ligand by similar to200-fold in magnitude and similar to400-fold in rate within 4 h (ligand internalization t(1/2) similar to 95 min at 37 degreesC). This non-natural receptor mimics many natural receptors by dynamically cycling between plasma membranes and intracellular endosomes (recycling t(1/2) similar to 3 min), targeting of protein ligands to proposed cholesterol and sphingolipid-enriched lipid raft membrane microdomains, and delivery of protein ligands to late endosomes/lysosomes. Quantitative dithionite quenching of fluorescent extracellular NBD headgroups demonstrated that other 3beta-cholesterylamine derivatives bearing fewer beta-alanines in the linker region or N-acyl derivatives of 3beta-cholesterylamine were less effective receptors due to more extensive trafficking to internal membranes. Synthetic cell surface receptors have potential applications as cellular probes, tools for drug delivery, and methods to deplete therapeutically important extracellular ligands.

  DOI：

  10.1021/ja046663o
• 作为产物：
  描述：

  胆固醇 在 叠氮基三甲基硅烷 、 三氟化硼乙醚 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 3β-azido-5-cholestene
  参考文献：
  名称：

  1,5,7-三氮杂双环[4.4.0]dec-5-ene：内酯氨解形成酰胺的有效催化剂

  摘要：

  酰胺是天然和工程化学领域最普遍的官能团之一。在构建酰胺键的各种方法中，内酯氨解仍然是最经济的原子经济方法之一。在此，我们报道了 1,5,7-三氮杂双环[4.4.0]dec-5-ene (TBD) 作为温和条件下内酯氨解的有效催化剂。该方法与多种内酯和胺（> 50 个示例）兼容，包括各种天然产物和药物，并且适用于生物活性分子的合成。在综合相关条件下的详细机理研究，包括反应进程动力学分析和可变时间归一化分析，揭示了涉及酰基-TBD作为反应中间体的该反应的可能机制。

  DOI：

  10.1021/acs.joc.3c00913

文献信息

• [EN] CELLULAR SIGNALLING INHIBITORS, THEIR FORMULATIONS AND METHODS THEREOF<br/>[FR] INHIBITEURS DE SIGNALISATION CELLULAIRE, LEURS FORMULES ET LEURS PROCÉDÉS
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2017137958A1

  公开（公告）日：2017-08-17

  The present disclosure relates generally to Cellular Signalling inhibitors of compound of Formula (I), compositions and formulations comprising the same, methods, processes, and uses thereof. In particular, the present disclosure provides CSF-1R inhibitors demonstrating sustained inhibition of CSF/CSF1R signalling pathway with decreased toxicity. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a CSF-1R inhibitor is combined with one or more of a chemotherapeutic agent, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid. The present disclosure also provides a method for treating cancer, allergy, Systemic lupus erythematosus, nephritis, Chronic Obstructive Pulmonary Disease, and abnormal macrophage functions or any combinations thereof.

  本公开涉及一般细胞信号传导抑制剂，涉及式(I)的化合物、包含该化合物的组合物和制剂、以及它们的方法、过程和使用。特别是，本公开提供了CSF-1R抑制剂，它们表现出对CSF/CSF1R信号通路的持续抑制，并且毒性降低。本公开还提供了超分子组合疗法，其中CSF-1R抑制剂与一个或多个化疗剂、激酶抑制剂和免疫调节剂结合，其中每个可选地与脂质偶联。本公开还提供了一种治疗癌症、过敏、系统性红斑狼疮、肾炎、慢性阻塞性肺病和异常巨噬细胞功能或其任何组合的方法。
• Carboxylate-Assisted Iridium-Catalyzed C−H Amination of Arenes with Biologically Relevant Alkyl Azides
  作者：Tao Zhang、Xuejiao Hu、Zhen Wang、Tiantian Yang、Hao Sun、Guigen Li、Hongjian Lu

  DOI：10.1002/chem.201504880

  日期：2016.2.24

  wide substrate scope is reported. Benzamides with electron‐donating and ‐withdrawing groups and linear, branched, and cyclic alkyl azides are all applicable. Cesium carboxylate is crucial for both reactivity and regioselectivity of the reactions. Many biologically relevant molecules, such as amino acid, peptide, steroid, sugar, and thymidine derivatives can be introduced to arenes with high yields and

  据报道，铱催化的芳烃CHH胺化具有广泛的底物范围。具有给电子和吸电子基团以及线性，支化和环状烷基叠氮化物的苯甲酰胺均适用。羧酸铯对于反应的反应性和区域选择性都至关重要。许多生物学上相关的分子，例如氨基酸，肽，类固醇，糖和胸苷衍生物，都可以高收率和100％手性保留率引入芳烃。
• Click Chemistry: An Efficient Synthesis of Heterocycles Substituted with Steroids, Saponins, and Digitalis Analogues
  作者：Márcio Paixão、Anna Deobald、Leandro Camargo、Diego Alves、Julio Zukerman-Schpector、Arlene Corrêa

  DOI：10.1055/s-0031-1289606

  日期：2011.12

  partner allowed the synthesis of a privileged class of natural product analogues. The versatility of this protocol makes this chemistry a useful attractive approach for the synthesis of target molecules. click chemistry - 1,2,3-triazole - sugars - steroids - saponins - digitalis

  铜催化的叠氮化物-炔烃环加成反应（CuAAC）已用于高产，高产的含1,2,3-三唑类固醇的构建。炔丙基糖苷和甾类叠氮化物作为反应伴侣的组合允许合成一类特权的天然产物类似物。该方案的多功能性使该化学成为合成目标分子的有用的有吸引力的方法。 点击化学-1,2,3-三唑-糖-类固醇-皂苷-洋地黄
• Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners
  作者：Mohamed Ramadan El Sayed Aly、Hosam Ali Saad、Shams Hashim Abdel-Hafez

  DOI：10.3762/bjoc.11.208

  日期：——

  3β-Azidocholest-5-ene (3) and (3β)-3-(prop-2-yn-1-yloxy)cholest-5-ene (10) were prepared as substrates to synthesize a variety of three-motif pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro.

  3β-氮杂胆甾-5-烯（3）和（3β）-3-(丙-2-炔-1-氧基)胆甾-5-烯（10）被制备为底物，以合成各种三基团药效团结合物通过CuAAC。基本上，这些结合物包括胆固醇和1,2,3-三唑基团，而第三个药效团则是香豆素、疏水残基或碳水化合物标记中的一个。这些化合物以良好的产率成功制备，并通过NMR、MS和IR光谱技术进行表征。香豆素结合物6c显示出最佳的抗微生物活性，而乳糖苷结合物27在体外显示出最佳的细胞毒作用。
• Redox-Neutral P(O)–N Coupling between P(O)–H Compounds and Azides via Dual Copper and Photoredox Catalysis
  作者：Yanan Wu、Ken Chen、Xia Ge、Panpan Ma、Zhiyuan Xu、Hongjian Lu、Guigen Li

  DOI：10.1021/acs.orglett.0c02207

  日期：2020.8.7

  We report a redox-neutral P(O)–N coupling reaction of P(O)–H compounds with azides via photoredox and copper catalysis, providing new access to useful phosphinamides, phosphonamides, and phosphoramides. This transformation tolerates a wide range of nucleophilic functionalities including alcohol and amine nucleophiles, which makes up for the deficiency of classical nitrogen nucleophilic substitution

  我们报道了P（O）-H化合物与叠氮化物通过光氧化还原和铜催化的氧化还原中性P（O）-N偶联反应，提供了获得有用的次膦酰胺，膦酰胺和磷酰胺的新途径。这种转化可耐受多种亲核功能，包括醇和胺亲核，这弥补了传统氮亲核取代反应的不足。为了证明这种新方法的广泛潜在应用，已开发了多种含叠氮基天然产物和药物分子的后期功能化，初步的不对称反应和连续的可见光光流过程。