MeOCO-Gly-DL-N(Ph(3-F))Phg(2-Me)-NHcHex | 1355327-34-2

• 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: MeOCO-Gly-DL-N(Ph(3-F))Phg(2-Me)-NHcHex
• 英文别名: methyl N-[2-(N-[2-(cyclohexylamino)-1-(2-methylphenyl)-2-oxoethyl]-3-fluoroanilino)-2-oxoethyl]carbamate
• CAS: 1355327-34-2
• 化学式: C₂₅H₃₀FN₃O₄
• 分子量: 455.529
• InChiKey: HUFPYGZRRXUWKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  、 氯甲酸甲酯 在 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 MeOCO-Gly-DL-N(Ph(3-F))Phg(2-Me)-NHcHex
  参考文献：
  名称：

  Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.7b00421

文献信息

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

  公开号：US20130184222A1

  公开（公告）日：2013-07-18

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

  提供了一种治疗癌症的方法，其特征在于存在IDH1基因突变等位基因，包括向需要此类治疗的受试者施用此处所述的化合物。