(S)-2,4-diamino-6-(((5-chloro-8-fluoro-4-oxo-3-(pyridin-3-yl)-3,4-dihydroquinazolin-2-yl) (cyclopropyl)methyl)amino)pyrimidine-5-carbonitrile | 1640247-87-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (S)-2,4-diamino-6-(((5-chloro-8-fluoro-4-oxo-3-(pyridin-3-yl)-3,4-dihydroquinazolin-2-yl) (cyclopropyl)methyl)amino)pyrimidine-5-carbonitrile
• 英文别名: Gs-9901；2,4-diamino-6-[[(S)-(5-chloro-8-fluoro-4-oxo-3-pyridin-3-ylquinazolin-2-yl)-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile
• CAS: 1640247-87-5
• 化学式: C₂₂H₁₇ClFN₉O
• 分子量: 477.888
• InChiKey: XDSXYMOZKDUASY-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  Boc-L-环丙基甘氨酸 在 吡啶 、 potassium fluoride 、 diphenyl phosphite 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 吡啶 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 (S)-2,4-diamino-6-(((5-chloro-8-fluoro-4-oxo-3-(pyridin-3-yl)-3,4-dihydroquinazolin-2-yl) (cyclopropyl)methyl)amino)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Discovery of Orally Efficacious Phosphoinositide 3-Kinase δ Inhibitors with Improved Metabolic Stability

  摘要：

  Aberrant signaling of phosphoinositide 3-kinase delta (PI3K delta) has been implicated in numerous pathologies including hematological malignancies and rheumatoid arthritis. Described in this manuscript are the discovery, optimization, and in vivo evaluation of a novel series of pyridine-containing PI3K delta inhibitors. This work led to the discovery of 35, a highly selective inhibitor of PI3K delta which displays an excellent pharmacokinetic profile and is efficacious in a rodent model of rheumatoid arthritis.

  DOI：

  10.1021/acs.jmedchem.6b01169

文献信息

• PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
  申请人：Gilead Sciences, Inc.

  公开号：US20140371246A1

  公开（公告）日：2014-12-18

  The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts or isomers thereof, in which n, m, R 1 , R 2 , R 4 , and R 3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts or isomers thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.

  本公开提供了式（I）的磷脂酰肌醇3-激酶（PI3K）抑制剂，或其药用盐或异构体，其中n、m、R1、R2、R4和R3如本文所定义。这些化合物可用于治疗由一个或多个PI3K同工酶介导的疾病，如PI3Kδ。本公开还提供了包括式（I）的化合物、药用盐或异构体的药物组合物，以及使用这些化合物和组合物治疗由一个或多个PI3K同工酶介导的疾病，如PI3Kδ的方法。
• FORMULATION OF SYK INHIBITORS
  申请人：Gilead Connecticut, Inc.

  公开号：US20150038504A1

  公开（公告）日：2015-02-05

  Disclosed are pharmaceutical compositions comprising a compound having the formula: or a pharmaceutically acceptable salt thereof, or a hydrate of thereof, and at least one pharmaceutically acceptable polymer. The pharmaceutically acceptable salt of the compound of Formula I, or a hydrate thereof, can be a mesylate salt, including, for example, a mono-mesylate or a bis-mesylate salt, or a hydrate thereof. Also disclosed are methods of use for the pharmaceutical composition.

  本发明涉及一种药物组合物，包括下列化合物之一：或其药学上可接受的盐，或其水合物，以及至少一种药学上可接受的聚合物。化合物I的药学上可接受的盐或其水合物可以是甲磺酸盐，例如单甲磺酸盐或双甲磺酸盐，或其水合物。本发明还涉及该药物组合物的使用方法。
• POLYMORPH OF SYK INHIBITORS
  申请人：Gilead Connecticut, Inc.

  公开号：US20150038505A1

  公开（公告）日：2015-02-05

  Polymorphs of a bis-mesylate salt of a compound of Formula I: or a hydrate thereof, are provided. The bis-mesylate salt may also be depicted as a compound of Formula IA: Provided herein are also compositions thereof, methods for their preparation and methods for such polymorphs.

  本文提供了化合物I的双甲磺酸盐的多态性或其水合物。双甲磺酸盐也可表示为化合物IA。本文还提供了其组合物、制备方法和多晶形态的制备方法。
• [EN] PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHATIDYLINOSITOL 3-KINASE
  申请人：GILEAD SCIENCES INC

  公开号：WO2014201409A1

  公开（公告）日：2014-12-18

  The present disclosure provides phosphatidylinositol 3 -kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts or isomers thereof, in which n, m, R1, R2, R4, and R3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts or isomers thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.

  本公开提供式(I)的磷脂酰肌醇3-激酶（PI3K）抑制剂，或其药学上可接受的盐或异构体，其中n，m，R1，R2，R4和R3如本文所定义。这些化合物可用于治疗由一个或多个PI3K亚型介导的疾病，例如PI3Kδ。本公开还提供包括式(I)的化合物或其药学上可接受的盐或异构体的制药组合物，以及使用这些化合物和组合物治疗由一个或多个PI3K亚型介导的疾病，例如PI3Kδ的方法。
• Polymorph of Syk inhibitors
  申请人：Gilead Connecticut, Inc.

  公开号：US10266539B2

  公开（公告）日：2019-04-23

  Polymorphs of a bis-mesylate salt of a compound of Formula I: or a hydrate thereof, are provided. The bis-mesylate salt may also be depicted as a compound of Formula IA: Provided herein are also compositions thereof, methods for their preparation and methods for such polymorphs.

  式 I 化合物的双甲磺酸盐的多晶型： 或其水合物的多晶型。双甲磺酸盐也可描述为式 IA 的化合物： 本文还提供了其组合物、其制备方法以及此类多晶体的制备方法。