塞尔帕替尼 | 2222755-14-6

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 塞尔帕替尼
• 英文名称: 4-(5-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyrazin-2-yl)-6-(((R)-morpholin-2-yl)methoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile
• 英文别名: LOXO-292；Ret-IN-1；4-[5-[6-[(6-methoxypyridin-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]pyrazin-2-yl]-6-[[(2R)-morpholin-2-yl]methoxy]pyrazolo[1,5-a]pyridine-3-carbonitrile
• CAS: 2222755-14-6
• 化学式: C₂₉H₃₁N₉O₃
• 分子量: 553.624
• InChiKey: GTQISTQEBXXLPC-UBVWURDFSA-N

物化性质

• 密度：
  1.49±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  11

制备方法与用途

简介

近日，美国食品和药物管理局(FDA)受理塞尔帕替尼(LOXO-292)的新药申请(NDA)并授予了优先审查，该靶向药是一种口服RET激酶抑制剂，用于治疗晚期RET融合阳性非小细胞肺癌(NSCLC)患者、RET突变型甲状腺髓样癌(MTC)患者、RET融合阳性甲状腺癌患者。

用途

塞尔帕替尼(LOXO-292)是一种强效、口服、高度选择性转染期间重排(RET)激酶抑制剂，用于治疗RET异常的癌症患者。RET基因是一个在转染过程中发生重排的原癌基因，并因此而得名，该基因编码一种细胞膜受体酪氨酸激酶，其异常是多种类型肿瘤的罕见驱动因素。

文献信息

• [EN] SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS SUBSTITUÉS DE PYRAZOLO[1,5-A]PYRIDINE EN TANT QU'INHIBITEURS DE LA KINASE RET
  申请人：ANDREWS STEVEN W

  公开号：WO2018071447A1

  公开（公告）日：2018-04-19

  Provided herein are compounds of the Formula I and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, X1, X2, X3, X4, Ring D, and E 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.

  本文件提供了公式I的化合物以及立体异构体和药用可接受的盐或溶剂化物，其中A、B、X1、X2、X3、X4、环D和E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，包括与RET相关疾病和失调。
• Substituted pyrazolo[1,5-a]pyridine compounds as RET kinase inhibitors
  申请人：Array BioPharma, Inc.

  公开号：US10137124B2

  公开（公告）日：2018-11-27

  Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, X1, X2, X3, X4, Ring D, and E 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.

  本文提供了公式I的化合物，其立体异构体和药学上可接受的盐或溶剂，其中A、B、X1、X2、X3、X4、环D和E在规范中给出的含义，它们是RET激酶的抑制剂，并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相关的疾病和障碍。
• Substituted pyrazolo[1,5-A]pyridine compounds as RET kinase inhibitors
  申请人：Array BioPharma, Inc.

  公开号：US10112942B2

  公开（公告）日：2018-10-30

  Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, X1, X2, X3, X4, Ring D, and E 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.

  本文提供的是式 I 的化合物： 及其立体异构体和药学上可接受的盐或溶液，其中 A、B、X1、X2、X3、X4、环 D 和 E 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以用 RET 激酶抑制剂治疗的疾病，包括 RET 相关疾病和紊乱。
• SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
  申请人：Array Biopharma Inc.

  公开号：EP3523301B1

  公开（公告）日：2020-05-27
• TREATMENT OF CANCERS HAVING DRIVING ONCOGENIC MUTATIONS
  申请人：G1 Therapeutics, Inc.

  公开号：US20210030758A1

  公开（公告）日：2021-02-04

  Methods and compositions are described to treat a cancer having a specific oncogenic driving mutation by administering a CDK4/6 inhibitor in combination with an additional kinase inhibitor, wherein the specific combination provides advantageous or synergistic inhibitory activity, delays acquired resistance to the additional kinase inhibitor, and/or extends the efficacy of the kinase inhibitor.