N-(5-{2-[(1S)-1-cyclopropylethyl]-7-[(methylsulfonyl)amino]-1-oxo-2,3-dihydro-1H-isoindol-5-yl}-4-methyl-1,3-thiazol-2-yl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(5-{2-[(1S)-1-cyclopropylethyl]-7-[(methylsulfonyl)amino]-1-oxo-2,3-dihydro-1H-isoindol-5-yl}-4-methyl-1,3-thiazol-2-yl)acetamide
• 英文别名: N-[5-[2-[(1S)-1-cyclopropylethyl]-7-(methanesulfonamido)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]acetamide
• 化学式: C₂₀H₂₄N₄O₄S₂
• 分子量: 448.567
• InChiKey: RMZMULPZUXWJGE-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-乙酰氨基-4-甲基噻唑 在 palladium diacetate 、 caesium carbonate 、 sodium t-butanolate 、 tri tert-butylphosphoniumtetrafluoroborate 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 N-(5-{2-[(1S)-1-cyclopropylethyl]-7-[(methylsulfonyl)amino]-1-oxo-2,3-dihydro-1H-isoindol-5-yl}-4-methyl-1,3-thiazol-2-yl)acetamide
  参考文献：
  名称：

  高度同工型选择性口服生物利用性磷酸肌醇3-激酶（PI3K）-γ抑制剂的发现。

  摘要：

  在本文中，我们描述了同工型选择性PI3Kγ抑制剂的新型化学型的发现和优化。从命中率开始，药效和理化性质可以得到改善，以得到化合物15等，这是一种有效且显着选择性的PI3Kγ抑制剂，具有适合口服的ADME特性。化合物15进入体内研究，显示口服给药时大鼠对LPS诱导的气道中性粒细胞减少的剂量依赖性抑制。

  DOI：

  10.1021/acs.jmedchem.8b00447

文献信息

• [EN] NOVEL INHIBITORS OF PHOSPHATIDYLINOSITOL 3-KINASE GAMMA<br/>[FR] NOUVEAUX INHIBITEURS DE LA PHOSPHATIDYLINOSITOL 3-KINASE GAMMA
  申请人：ASTRAZENECA AB

  公开号：WO2017153527A1

  公开（公告）日：2017-09-14

  There are disclosed certain novel compounds (including pharmaceutically acceptable salts thereof), that inhibit phosphatidylinositol 3-kinase gamma (ΡΒΚγ) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

  已披露某些新颖化合物（包括其药用盐），这些化合物抑制磷脂酰肌醇3-激酶γ（PI3Kγ）的活性，用于治疗和/或预防临床疾病，包括呼吸道疾病，如哮喘和慢性阻塞性肺病（COPD），以及它们在治疗中的用途，包含它们的药物组合物和制备这些化合物的过程。
• Inhibitors of phosphatidylinositol 3-kinase gamma
  申请人：AstraZeneca AB

  公开号：US10858355B2

  公开（公告）日：2020-12-08

  There are disclosed certain novel compounds (including pharmaceutically acceptable salts thereof), that inhibit phosphatidylinositol 3-kinase gamma (PI3Kδ) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

  本文公开了某些新型化合物（包括其药学上可接受的盐）、 抑制磷脂酰肌醇 3- 激酶γ（PI3Kδ）活性的化合物，它们在治疗和/或预防包括呼吸系统疾病（如哮喘和慢性阻塞性肺病（COPD））在内的临床疾病中的用途，它们在治疗中的使用，含有它们的药物组合物，以及制备此类化合物的工艺。
• NOVEL INHIBITORS OF PHOSPHATIDYLINOSITOL 3-KINASE GAMMA
  申请人：Astrazeneca AB

  公开号：EP3426652B1

  公开（公告）日：2021-12-01
• INHIBITORS OF PHOSPHATIDYLINOSITOL 3-KINASE GAMMA
  申请人：AstraZeneca AB

  公开号：US20210047312A1

  公开（公告）日：2021-02-18

  There are disclosed certain novel compounds (including pharmaceutically acceptable salts thereof), that inhibit phosphatidylinositol 3-kinase gamma (PI3Kδ) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.
• PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
  申请人：NANJING ZHENGXIANG PHARMACEUTICALS CO., LTD.

  公开号：US20220220113A1

  公开（公告）日：2022-07-14

  The present disclosure provides selective phosphoinositide 3-kinase gamma inhibitors of Formula (I) including (I-a), (I-b), (I-c), and (I-d), or pharmaceutically acceptable salts thereof. These compounds are useful for the treatment of conditions mediated by one or more PI3K isoforms, such as PI3K gamma (PI3Kγ). The present disclosure further provides methods of inhibiting phosphoinositide 3-kinase gamma using these compounds for treatment of disorders related to phosphatidylinositol 3-kinase gamma activity.