(4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide | 2821793-99-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide
• 英文别名: KRAS G12D inhibitor 17；(2S,4R)-1-[(2S)-2-[4-[4-[[6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-(oxan-4-yloxy)quinazolin-8-yl]oxymethyl]phenyl]triazol-1-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
• CAS: 2821793-99-9
• 化学式: C₆₀H₆₅FN₁₂O₇S
• 分子量: 1117.32
• InChiKey: XXWMEQMGQNHRAF-WFJRNIGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  81
• 可旋转键数：
  17
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  259
• 氢给体数：
  5
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 以1.04 g的产率得到(4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methyl butanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide hydrochloric acid
  参考文献：
  名称：

  Ｇ１２Ｄ変異ＫＲＡＳタンパクの分解を誘導するためのキナゾリン化合物

  摘要：

  【課題】提供一种作为胰腺癌治疗药物组合物有效成分的有用化合物。 【解决方案】本发明人员研究了作为胰腺癌治疗药物组合物有效成分的有用化合物，发现了喹啉化合物具有诱导优良的G12D突变KRAS蛋白降解作用和G12D突变KRAS抑制活性，可以用作胰腺癌治疗药物，完成了本发明。本发明的喹啉化合物或其盐可用作胰腺癌的治疗药物。 【选定图】无

  公开号：

  JP2022191505A
• 作为产物：
  描述：

  tert-butyl (1S,4S)-5-{6-cyclopropyl-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-{[4-(1-{(2S)-1-[(2S,4R)-4-hydroxy-2-({(lR)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}carbamoyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yI}-1H-1,2,3-triazol-4-yl)phenyl]methoxy}-2-[(oxan-4-yl)oxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以3.01 g的产率得到(4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide
  参考文献：
  名称：

  [EN] COMBINATION OF ANTICANCER AGENTS COMPRISING A BIFUNCTIONAL COMPOUND WITH G12D MUTANT KRAS INHIBITORY ACTIVITY
  [FR] ASSOCIATION D'AGENTS ANTICANCÉREUX COMPRENANT UN COMPOSÉ BIFONCTIONNEL AYANT UNE ACTIVITÉ INHIBITRICE DE KRAS MUTANT G12D

  摘要：

  There is provided herein a combination of compound of formula (I), which is a bifunctional compound with G12D mutant KRAS inhibitory activity, or a pharmaceutically acceptable salt thereof, and an anti-cancer agent for use in the treatment of cancer, wherein the compound of formula (I) and the anti-cancer agent are as described in the description.

  公开号：

  WO2024033537A1

文献信息

• [EN] PHARMACEUTICAL COMPOSITION COMPRISING A QUINAZOLINE COMPOUND<br/>[FR] COMPOSITION PHARMACEUTIQUE COMPRENANT UN COMPOSÉ QUINAZOLINE
  申请人：[en]ASTELLAS PHARMA INC.

  公开号：WO2023119677A1

  公开（公告）日：2023-06-29

  The present invention has an object to provide a pharmaceutical composition for treating a cancer of colorectal cancer and/or lung cancer. The present inventors have studied about a compound that is useful as an active ingredient of a pharmaceutical composition for treating a cancer, and have found that a quinazoline compound has an excellent degradation-inducing action on a G12D mutant KRAS protein and a G12D mutant KRAS inhibition activity and that a pharmaceutical composition containing the compound as an active ingredient can be used as a therapeutic agent for a cancer, completing the present invention. The pharmaceutical composition of the present invention which contains a quinazoline compound or a salt thereof as an active ingredient can be used as a therapeutic agent for a cancer of colorectal cancer and/or lung cancer.