4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde
• 英文别名: 4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2-hydroxy-5-methylbenzaldehyde；4-((3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde；4-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy]-2-hydroxy-5-methylbenzaldehyde
• 化学式: C₂₄H₂₂O₅
• 分子量: 390.436
• InChiKey: ZKWKWQMIJMPBDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde 在 sodium cyanoborohydride 、 caesium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (2R)-2-[({2-[(3-cyanophenyl)methoxy]-4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-5-methylphenyl}methyl)amino]-3-hydroxypropanoic acid hydrochloride
  参考文献：
  名称：

  Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1

  摘要：

  Blockade of the PD-1/PD-L1 immune checkpoint pathway with monoclonal antibodies has provided significant advances in cancer treatment. The antibody-based immunotherapies carry a number of disadvantages such as the high cost of the antibodies, their limited half-life, and immunogenicity. Development of small-molecule PD-1/PD-L1 inhibitors that could overcome these drawbacks is slow because of the incomplete structural information for this pathway. The first chemical PD-1/PD-L1 inhibitors have been recently disclosed by Bristol-Myers Squibb. Here we present NMR and X-ray characterization for the two classes of these inhibitors. The X-ray structures of the PD-L1/inhibitor complexes reveal one inhibitor molecule located at the center of the PD-L1 homodimer, filling a deep hydrophobic channel-like pocket between two PD-L1 molecules. Derivatives of (2-methyl-3-biphenylyl)methanol exhibit the structures capped on one side of the channel, whereas the compounds based on [3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methanol induce an enlarged interaction interface that results in the open face-back tunnel through the PD-L1 dimer.

  DOI：

  10.1021/acs.jmedchem.7b00293
• 作为产物：
  描述：

  3-溴-2-甲基苯甲醇 在 potassium phosphate 、 偶氮二甲酸二异丙酯 、 XPhos Pd G2 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 生成 4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde
  参考文献：
  名称：

  Compounds Useful as Immunomodulators

  摘要：

  本公开涉及一般用作免疫调节剂的化合物。提供的是包含这些化合物的化合物、组合物以及它们的使用方法。本公开还涉及包含至少一种根据本公开的化合物的药物组合物，用于治疗各种疾病，包括癌症和传染病。

  公开号：

  US20150291549A1
• 作为试剂：
  描述：

  三苯基膦 、 (3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylphenyl)methanol 、 2,4-dihydroxy-5-methylbenzaldehyde 、 偶氮二甲酸二异丙酯 在 silica gel 、 4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde 作用下， 以 四氢呋喃 为溶剂， 反应 16.25h， 以to give a white solid as the final product 4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde (85 mg, 0.218 mmol, 33.1% yield)的产率得到4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-hydroxy-5-methylbenzaldehyde
  参考文献：
  名称：

  Compounds Useful as Immunomodulators

  摘要：

  本公开涉及通常用作免疫调节剂的化合物。本文提供了包含这些化合物的组合物以及它们的使用方法。本公开进一步涉及包括至少一种根据本公开的化合物的制药组合物，用于治疗各种疾病，包括癌症和传染病。

  公开号：

  US20150291549A1

文献信息

• [EN] COMPOUND WITH BENZYLOXY AROMATIC RING STRUCTURE, PREPARATION METHOD AND USE THEREOF<br/>[FR] COMPOSÉ AYANT UNE STRUCTURE BENZYLOXY CYCLIQUE AROMATIQUE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 一种具有苄氧基芳环结构的化合物，其制备方法和用途
  申请人：SHANGHAI INST MATERIA MEDICA CAS

  公开号：WO2020244518A1

  公开（公告）日：2020-12-10

  本发明提供了一种通式(I)所示的苄氧基芳环结构的化合物，其立体异构体、对映体或其药学上可接受的盐，其制备方法，包含其的药物组合物及其用途。所述通式(I)所示的化合物可用于制备PD1/PD-L1相互作用的小分子抑制剂，其可用于预防和/或治疗与PD1/PD-L1相互作用相关的疾病，尤其是癌症，例如，尤其是非小细胞肺癌、小细胞肺癌、黑色素瘤、头颈癌、肾癌、膀胱癌、局部晚期或转移性尿路上皮癌、乳腺癌、宫颈癌、转移性默克尔细胞癌、前列腺癌、肝癌、肠癌、胃癌、多发性骨髓瘤、套细胞淋巴癌、弥漫性大B细胞淋巴瘤肝癌、霍奇金淋巴瘤、慢性淋巴细胞白血病、鳞状细胞癌等癌症。
• COMPOUNDS USEFUL AS IMMUNOMODULATORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP3131876A2

  公开（公告）日：2017-02-22
• US9850225B2
  申请人：——

  公开号：US9850225B2

  公开（公告）日：2017-12-26
• [EN] COMPOUNDS USEFUL AS IMMUNOMODULATORS<br/>[FR] COMPOSÉS UTILES COMME IMMUNOMODULATEURS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015160641A2

  公开（公告）日：2015-10-22

  The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.
• Compounds Useful as Immunomodulators
  申请人：Bristol-Myers Squibb Company

  公开号：US20150291549A1

  公开（公告）日：2015-10-15

  The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

  本公开涉及一般用作免疫调节剂的化合物。提供的是包含这些化合物的化合物、组合物以及它们的使用方法。本公开还涉及包含至少一种根据本公开的化合物的药物组合物，用于治疗各种疾病，包括癌症和传染病。