5-[8,9-二氢-6,6-二甲基-4-(4-吗啉基)-6H-[1,4]恶嗪并[4,3-e]嘌呤-2-基]-2-嘧啶胺 | 1382979-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 5-[8,9-二氢-6,6-二甲基-4-(4-吗啉基)-6H-[1,4]恶嗪并[4,3-e]嘌呤-2-基]-2-嘧啶胺
• 中文别名: 5-[8,9-二氢-6,6-二甲基-4-(4-吗啉基)-6H-[1,4]恶嗪并[4,3-E]嘌呤-2-基]-2-嘧啶胺；PI3K和MTOR抑制剂(GDC-0084)；PI3K和MTOCHEMICALBOOKR抑制剂(GDC-0084)；5-(6,6-二甲基-4-吗啉-8,9-二氢-6H-[1,4]恶嗪并[4,3-E]嘌呤-2-基)嘧啶-2-胺
• 英文名称: 5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine
• 英文别名: paxalisib；GDC-0084；5-(6,6-dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[3,4-e]purin-2-yl)pyrimidin-2-amine；5-(6,6-dimethyl-4-morpholin-4-yl-8,9-dihydropurino[8,9-c][1,4]oxazin-2-yl)pyrimidin-2-amine
• CAS: 1382979-44-3
• 化学式: C₁₈H₂₂N₈O₂
• 分子量: 382.425
• InChiKey: LGWACEZVCMBSKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-chloro-6-(morpholin-4-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 在 盐酸 、 正丁基锂 、 potassium phosphate monohydrate 、 XPhos Pd G2 、 异丙基氯化镁 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 为溶剂， 反应 20.5h， 生成 5-[8,9-二氢-6,6-二甲基-4-(4-吗啉基)-6H-[1,4]恶嗪并[4,3-e]嘌呤-2-基]-2-嘧啶胺
  参考文献：
  名称：

  Development of an Efficient, Safe, and Environmentally Friendly Process for the Manufacture of GDC-0084

  摘要：

  An improved, efficient process with a significantly reduced process mass intensity (PMI) led to the multikilogram synthesis of a brain penetrant PI3K inhibitor GDC-0084. Highlights of the synthesis include a phase transfer catalyzed annulation in water, an efficient Suzuki-Miyaura cross-coupling of a chloropyrimidine with an arylboronic acid using a low palladium catalyst loading, and the development of a controlled crystallization to provide the API. The process delivered GDC-0084 with low levels of both impurities and residual metals.

  DOI：

  10.1021/acs.oprd.6b00011

文献信息

• [EN] TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS TRICYCLIQUES INHIBITEURS DE PI3K ET PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012082997A1

  公开（公告）日：2012-06-21

  Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti- inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

  具有抗癌活性、抗炎活性或免疫调节特性的Formula I的三环PI3K抑制剂化合物被描述。描述了使用Formula I的三环PI3K抑制剂化合物进行体外、原位和体内诊断或治疗哺乳动物细胞、生物体或相关病理条件的方法。Formula I化合物包括立体异构体、几何异构体、互变异构体和其药用可接受盐。虚线表示可选的双键，至少有一条虚线是双键。取代基如所述。
• COMPOUNDS FOR THE TREATMENT OF BRAF-ASSOCIATED DISEASES AND DISORDERS
  申请人：Array BioPharma Inc.

  公开号：US20200407344A1

  公开（公告）日：2020-12-31

  Provided herein are compounds of the Formula I: and pharmaceutically acceptable salts, solvates and polymorphs thereof, wherein L, X 1 , R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined herein, for the treatment of BRAF-associated diseases and disorders, including BRAF-associated tumors, including malignant and benign BRAF-associated tumors of the CNS and malignant extracranial BRAF-associated tumors.

  本文提供了式I的化合物及其药用可接受的盐、溶剂合物和多晶形式，其中L、X1、R1、R2、R3、R4、R5和R6如本文所定义，用于治疗与BRAF相关的疾病和紊乱，包括BRAF相关的肿瘤，包括中枢神经系统的恶性和良性BRAF相关肿瘤以及恶性的颅外BRAF相关肿瘤。
• [EN] 4-OXO-3,4-DIHYDROQUINAZOLINON COMPOUNDS FOR THE TREATMENT OF BRAF-ASSOCIATED DISEASES AND DISORDERS<br/>[FR] COMPOSÉS DE 4-OXO-3,4-DIHYDROQUINAZOLINONE POUR LE TRAITEMENT DE MALADIES ET D'AFFECTIONS ASSOCIÉES À BRAF
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2021250521A1

  公开（公告）日：2021-12-16

  Provided herein is a compound of the Formula I: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7 and L are as defined herein, for the treatment of BRAF-associated diseases and disorders, including BRAF-associated tumors.

  本文提供了一种化合物，其化学式为I：或其药用可接受的盐，其中R1、R2、R3、R4、R5、R6、R7和L的定义如本文所述，用于治疗与BRAF相关的疾病和紊乱，包括与BRAF相关的肿瘤。
• TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Dotson Jennafer

  公开号：US20120171199A1

  公开（公告）日：2012-07-05

  Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

  本文描述了具有抗癌活性、抗炎活性或免疫调节特性的公式I的三环PI3k抑制剂化合物，更具体地具有PI3激酶调控或抑制活性。本文还描述了使用公式I的三环PI3K抑制剂化合物进行哺乳动物细胞、生物体或相关病理条件的体外、原位和体内诊断或治疗的方法。公式I化合物包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐。虚线表示可选的双键，至少有一条虚线是双键。取代基如所述。
• TRICYCLIC P13K INHIBITOR COMPOUNDS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：US20150079081A1

  公开（公告）日：2015-03-19

  Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

  本文描述了具有抗癌活性、抗炎活性或免疫调节特性，更具体地具有PI3激酶调节或抑制活性的公式I的三环PI3k抑制剂化合物。本文还描述了使用公式I的三环PI3K抑制剂化合物用于哺乳动物细胞、生物体或相关病理条件的体外、体内诊断或治疗的方法。公式I化合物包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐。虚线表示一个可选的双键，至少有一条虚线是双键。取代基如所述。