1-benzhydryl-3-hydroxyazetidine-3-carboxamide | 934665-18-6

• 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: 1-benzhydryl-3-hydroxyazetidine-3-carboxamide
• 英文别名: 1-(diphenylmethyl)-3-hydroxyazetidine-3-carboxamide
• CAS: 934665-18-6
• 化学式: C₁₇H₁₈N₂O₂
• 分子量: 282.342
• InChiKey: WDLNDYAKLKYVKA-UHFFFAOYSA-N

物化性质

• 沸点：
  481.7±45.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzhydryl-3-hydroxyazetidine-3-carboxamide 在 氢气 、 palladium(II) hydroxide 作用下， 以 甲醇 为溶剂， 30.0 ℃ 、310.27 kPa 条件下， 反应 5.0h， 生成 3-hydroxyazetidine-3-carboxamide
  参考文献：
  名称：

  [EN] ISOXAZOLE CARBOXAMIDE COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS D'ISOXAZOLE CARBOXAMIDE ET LEURS UTILISATIONS

  摘要：

  提供了一个化合物的化学式（I）或其药用盐，已被证明对治疗听力损失或平衡障碍有用：化学式（I），其中R1和Y的定义如下。

  公开号：

  WO2020058913A1
• 作为产物：
  描述：

  1-二苯甲基-3-羟基氮杂环丁烷盐酸盐 在 N-甲基吗啉 、 四丙基高钌酸铵 、 硫酸 、 N-甲基吗啉氧化物 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 28.0h， 生成 1-benzhydryl-3-hydroxyazetidine-3-carboxamide
  参考文献：
  名称：

  Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)

  摘要：

  The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and is constitutively activated or highly upregulated in many tumor types. Mutations associated with upstream pathway components RAS and Raf occur frequently and contribute to the oncogenic phenotype through activation of MEK and then ERK. Inhibitors of MEK have been shown to effectively block upregulated ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated early evidence of efficacy in the clinic for the treatment of cancer. Guided by structural insight, a strategy aimed at the identification of an optimal diphenylamine-based MEK inhibitor with an improved metabolism and safety profile versus PD-0325901 led to the discovery of development candidate 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo in preclinical models with sustained duration of action and is currently in early stage clinical trials. potency and efficacy in preclinical models with sustained duration of action and is currently in early stage clinical trials.

  DOI：

  10.1021/ml300049d

文献信息

• Synthesis and biological evaluation of α- and β-hydroxy substituted amino acid derivatives as potential mGAT1–4 inhibitors
  作者：Janina C. Andreß、Michael C. Böck、Georg Höfner、Klaus T. Wanner

  DOI：10.1007/s00044-020-02548-x

  日期：2020.8

  In this study, we report the synthesis and biological evaluation of a variety of α- and β-hydroxy substituted amino acid derivatives as potential amino acid subunits in inhibitors of GABA uptake transporters (GATs). In order to ensure that the test compounds adopt a binding pose similar to that presumed for related larger GAT inhibitors, lipophilic residues were introduced either at the amino nitrogen

  在这项研究中，我们报告了各种α-和β-羟基取代的氨基酸衍生物作为GABA吸收转运蛋白（GAT）抑制剂的潜在氨基酸亚基的合成和生物学评估。为了确保测试化合物具有与相关的较大的GAT抑制剂所假定的相似的结合姿势，在氨基氮原子或在醇官能团处引入了亲脂性残基。与参考N-丁基己二酸相比，发现几种合成的化合物分别对GAT亚型mGAT2，mGAT3和mGAT4表现出相似的抑制活性。因此，这些化合物可作为更复杂的GAT抑制剂未来开发的起点。
• Methods of using MEK inhibitors
  申请人：Lamb Peter

  公开号：US20080166359A1

  公开（公告）日：2008-07-10

  The present invention provides methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, in combination with other cancer treatments.

  本发明提供了一种通过给予I式化合物或其药学上可接受的盐或溶剂与其他癌症治疗相结合的方法来治疗癌症的方法。
• S1P receptor modulating compounds and use thereof
  申请人：Burli Roland

  公开号：US20080027036A1

  公开（公告）日：2008-01-31

  The present invention relates to compounds of the general formula (I) that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds may be used as immunomodulators, e.g., for treating or preventing diseases such as autoimmune and related immune disorders including systemic lupus erythematosus, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, type I diabetes, uveitis, psoriasis, myasthenia gravis, rheumatoid arthritis, non-glomerular nephrosis, hepatitis, Behçet's disease, glomerulonephritis, chronic thrombocytopenic purpura, hemolytic anemia, hepatitis and Wegner's granuloma; and for treating other conditions.

  本发明涉及一般式（I）的化合物，其具有作为S1P受体调节剂的活性，以及使用这种化合物来治疗与不适当的S1P受体活性相关的疾病。这些化合物可以用作免疫调节剂，例如，用于治疗或预防自身免疫和相关免疫紊乱疾病，包括系统性红斑狼疮、炎症性肠病，如克隆病和溃疡性结肠炎、1型糖尿病、葡萄膜炎、牛皮癣、重症肌无力、类风湿性关节炎、非肾小球性肾病、肝炎、Behçet病、肾小球肾炎、慢性血小板减少性紫癜、溶血性贫血、肝炎和Wegner肉芽肿；以及用于治疗其他疾病。
• S1P Receptor Modulating Compounds and Use Thereof
  申请人：Burli Roland

  公开号：US20110212940A1

  公开（公告）日：2011-09-01

  The present invention relates to compounds of the general formula (I) that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds may be used as immunomodulators, e.g., for treating or preventing diseases such as autoimmune and related immune disorders including systemic lupus erythematosus, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, type I diabetes, uveitis, psoriasis, myasthenia gravis, rheumatoid arthritis, non-glomerular nephrosis, hepatitis, Behçet's disease, glomerulonephritis, chronic thrombocytopenic purpura, hemolytic anemia, hepatitis and Wegner's granuloma; and for treating other conditions.

  本发明涉及一般式（I）的化合物，该化合物具有作为S1P受体调节剂的活性，以及使用这种化合物治疗与不适当的S1P受体活性相关的疾病。这些化合物可以用作免疫调节剂，例如，用于治疗或预防自身免疫和相关免疫性疾病，包括全身性红斑狼疮、炎症性肠病（如克罗恩病和溃疡性结肠炎）、1型糖尿病、葡萄膜炎、银屑病、重症肌无力、类风湿性关节炎、非肾小球性肾病、肝炎、Behçet病、肾小球肾炎、慢性血小板减少性紫癜、溶血性贫血、肝炎和Wegner肉芽肿；以及用于治疗其他疾病。
• Azetidines as MEK Inhibitors for the Treatment of Proliferative Diseases
  申请人：Aay Naing

  公开号：US20100249096A1

  公开（公告）日：2010-09-30

  Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof. Such compounds are MEK inhibitors and are useful in the treatment of proliferative diseases, such as cancer. Also disclosed are pharmaceutical compositions containing such compounds as well as methods of using the compounds and compositions of the invention in the treatment of cancer.

  本发明公开了式(I)的化合物及其药学上可接受的盐和溶剂化物。这些化合物是MEK抑制剂，可用于治疗增生性疾病，如癌症。本发明还公开了含有这些化合物的制药组合物，以及使用本发明的化合物和组合物治疗癌症的方法。