(S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one | 1429180-81-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one
• 英文别名: (4S)-3-(2-chloropyrimidin-4-yl)-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 1429180-81-3
• 化学式: C₁₀H₁₂ClN₃O₂
• 分子量: 241.677
• InChiKey: CMYCIRFZJKISNU-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 生成 (S)-3-(2-((1-(4-aminobenzyl)piperidin-4-yl)amino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one
  参考文献：
  名称：

  [EN] INHIBITORS OF MUTANT ISOCITRATE DEHYDROGENASES AND COMPOSITIONS AND METHODS THEREOF
  [FR] INHIBITEURS D'ISOCITRATE DÉSHYDROGÉNASES MUTANTES, COMPOSITIONS ET PROCÉDÉS CORRESPONDANTS

  摘要：

  该发明提供了用于治疗癌症或相关疾病或障碍的新型化合物，以及其制备和使用的药物组合物和方法。

  公开号：

  WO2018118793A1
• 作为产物：
  描述：

  2,4-二氯嘧啶 以 mineral oil 为溶剂， 生成 (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one
  参考文献：
  名称：

  EP3964508

  摘要：

  公开号：

文献信息

• 3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES AS INHIBITORS OF MUTANT IDH
  申请人：VESTAS WIND SYSTEMS A/S

  公开号：US20140235620A1

  公开（公告）日：2014-08-21

  The invention is directed to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 -R 6 are defined herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

  该发明涉及公式（I）的化合物或其药用盐，其中R1-R6在此处定义。该发明还涉及含有公式（I）化合物的组合物，以及利用这些化合物抑制具有新型活性的突变IDH蛋白。该发明还涉及利用公式（I）的化合物治疗与这些突变IDH蛋白相关的疾病或紊乱，包括但不限于细胞增殖紊乱，如癌症。
• QUINOLINONE PYRIMIDINES COMPOSITIONS AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS
  申请人：Forma Therapeutics, Inc.

  公开号：US20160083365A1

  公开（公告）日：2016-03-24

  The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, B, W 1 , W 2 , W 3 , and R 1 -R 6 are described herein.

  这项发明涉及对突变异构异柠檬酸脱氢酶（mt-IDH）蛋白的抑制剂，具有新陈代谢活性，可用于治疗细胞增殖紊乱和癌症，其化学式为：其中A、B、W1、W2、W3和R1-R6如本文所述。
• [EN] MUTANT IDH1 INHIBITORS<br/>[FR] INHIBITEURS DE LA IDH1 MUTANTE
  申请人：LILLY CO ELI

  公开号：WO2017213910A1

  公开（公告）日：2017-12-14

  The present application provides compounds of Formula I: Formula (I) that are useful as inhibitors of mutant IDH1, pharmaceutical compositions, and uses for the treatment of cancer.

  本申请提供了化合物的化学式I: 化学式(I)，这些化合物可用作突变IDH1的抑制剂，制药组合物，并用于治疗癌症。
• Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1
  作者：Julian R. Levell、Thomas Caferro、Gregg Chenail、Ina Dix、Julia Dooley、Brant Firestone、Pascal D. Fortin、John Giraldes、Ty Gould、Joseph D. Growney、Michael D. Jones、Raviraj Kulathila、Fallon Lin、Gang Liu、Arne Mueller、Simon van der Plas、Kelly Slocum、Troy Smith、Remi Terranova、B. Barry Touré、Viraj Tyagi、Trixie Wagner、Xiaoling Xie、Ming Xu、Fan S. Yang、Liping X. Zhou、Raymond Pagliarini、Young Shin Cho

  DOI：10.1021/acsmedchemlett.6b00334

  日期：2017.2.9

  throughput screening and subsequent hit validation identified 4-isopropyl-3-(2-((1-phenylethyl)amino)pyrimidin-4-yl)oxazolidin-2-one as a potent inhibitor of IDH1R132H. Synthesis of the four separate stereoisomers identified the (S,S)-diastereomer (IDH125, 1f) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs IDH1wt. Initial structure-activity relationship

  高通量筛选和随后的命中验证确定了4-异丙基-3-（2-（（（1-苯乙基）氨基）嘧啶-4-基）恶唑烷-2--2-酮是IDH1R132H的有效抑制剂。四种单独的立体异构体的合成确定了（S，S）-非对映异构体（IDH125，1f）是最有效的异构体。与IDH1wt相比，这也显示出合理的细胞活性和出色的选择性。初步的结构-活性关系探索确定了关键的公差和优化的潜力。X射线晶体学确定了一种适合抑制剂的功能相关的变构结合位点，该位点可以穿透血脑屏障，并有助于合理优化。增强效力并调节已鉴定的理化性质（S，
• [EN] 3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES AS INHIBITORS OF MUTANT IDH<br/>[FR] 3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES COMME INHIBITEURS D'IDH MUTANTE
  申请人：NOVARTIS AG

  公开号：WO2013046136A1

  公开（公告）日：2013-04-04

  The invention is directed to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1-R6 are defined herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formual (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

  该发明涉及公式(I)的化合物或其药学上可接受的盐，其中R1-R6在此处被定义。该发明还涉及含有公式(I)化合物的组合物，以及利用这些化合物抑制具有新型活性的突变IDH蛋白。该发明还涉及利用公式(I)的化合物治疗与这些突变IDH蛋白相关的疾病或紊乱，包括但不限于细胞增殖紊乱，如癌症。