3-(p-tolyl)azetidine | 7215-06-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: 3-(p-tolyl)azetidine
• 英文别名: 3-p-Tolyl-azetidin；AZETIDINE, 3-p-TOLYL-；3-(4-methylphenyl)azetidine
• CAS: 7215-06-7
• 化学式: C₁₀H₁₃N
• 分子量: 147.22
• InChiKey: BZYJWDPMIYLNOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(p-tolyl)azetidine 、 5-amino-3,4-dimethylthieno[2,3-c]pyridazine-6-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (5-Amino-3,4-dimethylthieno[2,3-c]pyridazin-6-yl)-[3-(4-methylphenyl)azetidin-1-yl]methanone
  参考文献：
  名称：

  Challenges in the development of an M 4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides

  摘要：

  Herein we describe the continued optimization of M-4 positive allosteric modulators (PAMs) within the 5-amino-thieno[2,3-c] pyridazine series of compounds. In this letter, we disclose our studies on tertiary amides derived from substituted azetidines. This series provided excellent CNS penetration, which had been challenging to consistently achieve in other amide series. Efforts to mitigate high clearance, aided by metabolic softspot analysis, were unsuccessful and precluded this series from further consideration as a preclinical candidate. In the course of this study, we found that potassium tetrafluoroborate salts could be engaged in a tosyl hydrazone reductive cross coupling reaction, a previously unreported transformation, which expands the synthetic utility of the methodology. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.053
• 作为产物：
  描述：

  tert-butyl 3-(p-tolyl)azetidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-(p-tolyl)azetidine
  参考文献：
  名称：

  发现新型联苯衍生物作为雄激素受体降解剂，用于治疗恩杂鲁胺耐药性前列腺癌

  摘要：

  第二代AR拮抗剂，例如恩杂鲁胺，是晚期前列腺癌的主要治疗药物。然而，原发性和继发性耐药性的发展导致治疗失败和患者死亡。同时拮抗和降解 AR 的双功能药物可以更完全地阻断 AR 信号通路，并对野生型和耐药性前列腺癌细胞表现出优异的抗增殖活性。在这里，我们报道了一系列作为雄激素受体拮抗剂和降解剂的联苯衍生物的发现和优化。这些联苯衍生物对 LNCaP 和 22Rv1 细胞表现出有效的抗增殖活性。我们的发现丰富了小分子 AR 降解剂的多样性，并为开发用于治疗恩杂鲁胺耐药性前列腺癌的新型 AR 降解剂提供了见解。

  DOI：

  10.1016/j.bioorg.2024.107433

文献信息

• 6-HYDROXY-4-OXO-1,4-DIHYDROPYRIMIDINE-5-CARBOXAMIDES AS APJ AGONISTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20170275272A1

  公开（公告）日：2017-09-28

  The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

  本发明提供了式（I）的化合物：其中所有变量如规范中所定义，并包括任何此类新化合物的组合物。这些化合物是APJ激动剂，可用作药物。
• NICOTINAMIDES AS JAK KINASE MODULATORS
  申请人：PORTOLA PHARMACEUTICALS, INC.

  公开号：US20150353495A1

  公开（公告）日：2015-12-10

  The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of JAK kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition JAK kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by JAK kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

  本发明涉及式I化合物及其药学上可接受的盐、酯和前药，它们是JAK激酶抑制剂。本发明还涉及用于制备这种化合物的中间体，制备这种化合物的方法，含有这种化合物的药物组合物，抑制JAK激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗至少部分由JAK激酶活性介导的多种疾病，如不良血栓形成和非霍奇金淋巴瘤的方法。
• 6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as APJ agonists
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10106528B2

  公开（公告）日：2018-10-23

  The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

  本发明提供了式 (I) 的化合物： 其中所有变量如说明书中所定义，以及包含任何此类新型化合物的组合物。这些化合物是可用作药物的 APJ 激动剂。
• NOVEL ARYL ETHANE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Daegu-Gyeongbuk Medical Innovation Foundation

  公开号：EP3459936B1

  公开（公告）日：2022-04-27
• NOVEL ARYL ETHENE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：NovMetaPharma Co., Ltd.

  公开号：EP3480186B1

  公开（公告）日：2022-06-15