(S)-(9H-fluoren-9-yl)methyl 2-(((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclo-butylamino)-2-oxoethyl)(3-fluorophenyl)carbamoyl)pyrrolidine-1-carboxylate | 1448310-12-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-(9H-fluoren-9-yl)methyl 2-(((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclo-butylamino)-2-oxoethyl)(3-fluorophenyl)carbamoyl)pyrrolidine-1-carboxylate
• 英文别名: (S)-(9H-fluoren-9-yl)methyl 2-(N-((S)-(3,3-difluoro-cyclobutylcarbamoyl)(2-chlorophenyl)methyl)-N-(3-fluorophenyl)carbamoyl)pyrrolidine-1-carboxylate；9H-fluoren-9-ylmethyl (2S)-2-[[(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl]-(3-fluorophenyl)carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1448310-12-0
• 化学式: C₃₈H₃₃ClF₃N₃O₄
• 分子量: 688.146
• InChiKey: SQQQFYGZZBNAGT-HEVIKAOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  49
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-(9H-fluoren-9-yl)methyl 2-(((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclo-butylamino)-2-oxoethyl)(3-fluorophenyl)carbamoyl)pyrrolidine-1-carboxylate 在 哌啶 作用下， 以 乙腈 为溶剂， 以57%的产率得到(S)-N-((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclobutylamino)-2-oxoethyl)-N-(3-fluorophenyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  [EN] THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
  [FR] COMPOSÉS THÉRAPEUTIQUEMENT ACTIFS ET LEURS MÉTHODES D'UTILISATION

  摘要：

  提供了一种治疗具有IDH1/2突变等特征的癌症的方法，包括向需要的受试者施用本处描述的化合物。

  公开号：

  WO2013107405A1
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 生成 (S)-(9H-fluoren-9-yl)methyl 2-(((S)-1-(2-chlorophenyl)-2-(3,3-difluorocyclo-butylamino)-2-oxoethyl)(3-fluorophenyl)carbamoyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
  [FR] COMPOSÉS THÉRAPEUTIQUEMENT ACTIFS ET LEURS MÉTHODES D'UTILISATION

  摘要：

  提供了一种治疗具有IDH1/2突变等特征的癌症的方法，包括向需要的受试者施用本处描述的化合物。

  公开号：

  WO2013107405A1

文献信息

• THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE
  申请人：Popovici-Muller Janeta

  公开号：US20150087600A1

  公开（公告）日：2015-03-26

  Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

  提供了一种治疗具有IDH1/2突变等特征的癌症的方法，包括向需要的受试者施用本文描述的化合物。
• Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers
  作者：Janeta Popovici-Muller、René M. Lemieux、Erin Artin、Jeffrey O. Saunders、Francesco G. Salituro、Jeremy Travins、Giovanni Cianchetta、Zhenwei Cai、Ding Zhou、Dawei Cui、Ping Chen、Kimberly Straley、Erica Tobin、Fang Wang、Muriel D. David、Virginie Penard-Lacronique、Cyril Quivoron、Véronique Saada、Stéphane de Botton、Stefan Gross、Lenny Dang、Hua Yang、Luke Utley、Yue Chen、Hyeryun Kim、Shengfang Jin、Zhiwei Gu、Gui Yao、Zhiyong Luo、Xiaobing Lv、Cheng Fang、Liping Yan、Andrew Olaharski、Lee Silverman、Scott Biller、Shin-San M. Su、Katharine Yen

  DOI：10.1021/acsmedchemlett.7b00421

  日期：2018.4.12

  Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of D-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired Mutant cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.
• [EN] THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE<br/>[FR] COMPOSÉS THÉRAPEUTIQUEMENT ACTIFS ET LEURS MÉTHODES D'UTILISATION
  申请人：AGIOS PHARMACEUTICALS INC

  公开号：WO2013107405A1

  公开（公告）日：2013-07-25

  Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

  提供了一种治疗具有IDH1/2突变等特征的癌症的方法，包括向需要的受试者施用本处描述的化合物。