2-(4-isopropyl-1,4-diazepan-1-yl)-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine | 1320288-45-6

• 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: 2-(4-isopropyl-1,4-diazepan-1-yl)-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine
• 英文别名: 6-methoxy-7-(3-piperidin-1-ylpropoxy)-2-(4-propan-2-yl-1,4-diazepan-1-yl)-N-(1-propan-2-ylpiperidin-4-yl)quinazolin-4-amine
• CAS: 1320288-45-6
• 化学式: C₃₃H₅₅N₇O₂
• 分子量: 581.845
• InChiKey: PMHNIDJCQQOZAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  69.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  苯甲酸,4-(3-氯丙氧基)-3-甲氧基-,甲基酯 在 ammonium acetate 、 水 、 硝酸 、 乙酸酐 、 四丁基碘化铵 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N,N-二乙基苯胺 、 sodium iodide 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 异丙醇 、 乙腈 为溶剂， 反应 10.25h， 生成 2-(4-isopropyl-1,4-diazepan-1-yl)-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine
  参考文献：
  名称：

  Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines

  摘要：

  Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.

  DOI：

  10.1021/jm200903z

文献信息

• [EN] SUBSTITUTED PYRAZOLYL[4,3-C]PYRIDINECOMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRAZOLYL[4,3-C]PYRIDINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2019143994A1

  公开（公告）日：2019-07-25

  Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2 and R3 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.

  提供以下式I的化合物：及其互变异构体和药用可接受的盐和溶剂化物，其中R1、R2和R3具有说明书中给出的含义，它们是RET激酶的抑制剂，可用于治疗和预防可通过RET激酶抑制剂治疗的疾病，包括RET相关疾病和失调。
• [EN] SUBSTITUTED PYRAZOLO[3,4-d]PYRIMIDINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRAZOLO[3,4-D]PYRIMIDINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2019143991A1

  公开（公告）日：2019-07-25

  Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R1 and R2 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.

  本文提供的是Formula I的化合物，以及其互变异构体和药学上可接受的盐和溶剂化合物，其中R1和R2具有规范中给定的含义，它们是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括与RET相关的疾病和疾病。
• Compositions and methods for the treatment of Prader-Willi syndrome
  申请人：Duke University

  公开号：US11278550B2

  公开（公告）日：2022-03-22

  The invention provides pharmaceutical compositions and methods of use thereof for treating Prader-Willi syndrome. More specifically, the invention provides pharmaceutical compositions that when administered inhibit the G9a driven methylation of histone H3 lysine 9.

  本发明提供了治疗普拉德-威利综合征的药物组合物及其使用方法。更具体地说，本发明提供的药物组合物给药后可抑制组蛋白 H3 赖氨酸 9 的 G9a 驱动的甲基化。
• Substituted pyrazolyl[4,3-c]pyridine compounds as RET kinase inhibitors
  申请人：Array BioPharma Inc.

  公开号：US11472802B2

  公开（公告）日：2022-10-18

  Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2 and R3 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.

  本文提供了式 I：及其同系物和药学上可接受的盐和溶液的化合物，其中 R1、R2 和 R3 具有说明书中给出的含义，它们是 RET 激酶的抑制剂，可用于治疗和预防可使用 RET 激酶抑制剂治疗的疾病，包括 RET 相关疾病和紊乱。
• Substituted pyrazolo[3,4-d]pyrimidines as RET kinase inhibitors
  申请人：Array Biopharma Inc.

  公开号：US11524963B2

  公开（公告）日：2022-12-13

  Provided herein are compounds of the Formula I: and tautomers and pharmaceutically acceptable salts and solvates thereof, wherein R 1 and R 2 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.

  本文提供了式 I 的化合物：及其同系物和药学上可接受的盐和溶剂，其中 R 1 和 R 2 具有说明书中给出的含义，它们是 RET 激酶的抑制剂，可用于治疗和预防可用 RET 激酶抑制剂治疗的疾病，包括 RET 相关疾病和紊乱。