6-cyano-3-fluoropyridin-2-yl acetate | 1189757-54-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-cyano-3-fluoropyridin-2-yl acetate
• 英文别名: (6-cyano-3-fluoropyridin-2-yl) acetate
• CAS: 1189757-54-7
• 化学式: C₈H₅FN₂O₂
• 分子量: 180.138
• InChiKey: FLCMDLBXJRJGQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  290.8±40.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• pKa：
  -5.99±0.22 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-cyano-3-fluoropyridin-2-yl acetate 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 (S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
  参考文献：
  名称：

  FT-2102（Olutasidenib）（一种有效的突变体选择性IDH1抑制剂）的基于结构的设计和鉴定。

  摘要：

  突变IDH1的抑制作用正在临床上作为肿瘤学的治疗选择进行评估。在这里，我们描述了基于喹啉化合物的结构设计和优化，以鉴定FT-2102，FT-2102是一种有效的，口服生物利用的，脑渗透剂和选择性mIDH1抑制剂。FT-2102具有出色的ADME / PK特性，并降低了mIDH1异种移植肿瘤模型中的2-羟基戊二酸水平。该化合物已被选为具有mIDH1的血液系统恶性肿瘤，实体瘤和神经胶质瘤临床开发的候选药物。

  DOI：

  10.1021/acs.jmedchem.9b01423
• 作为产物：
  描述：

  2-cyano-5-fluoropyridine 1-oxide 以60的产率得到6-cyano-3-fluoropyridin-2-yl acetate
  参考文献：
  名称：

  J. Med. Chem. 2020, 63, 1612−1623

  摘要：

  DOI：

文献信息

• TREATING PATIENTS HARBORING AN ISOCITRATE DEHYDROGENASE-1 (IDH-1) MUTATION
  申请人：FORMA Therapeutics, Inc.

  公开号：US20190350922A1

  公开（公告）日：2019-11-21

  Methods of treating patients diagnosed with AML or MDS harboring mutant IDH-1 include detecting an IDH1 mutation and the therapeutic administration of an inhibitor of a mutant IDH-1 as a single agent, or in combination with azacitidine (AZA) or cytarabine.

  治疗被诊断为携带突变IDH-1的AML或MDS患者的方法包括检测IDH1突变，并通过治疗给予突变IDH-1的抑制剂作为单一药物，或与阿扎胞苷（AZA）或环磷酰胺（cytarabine）联合使用。
• PYRIDIN-2(1H)-ONE QUINOLINONE DERIVATIVES AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS
  申请人：Forma Therapeutics, Inc.

  公开号：US20160083366A1

  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, U, W 1 , W 2 , W 3 , R 1 -R 6 , and R 9 are described herein.

  本发明涉及对突变异构己二酸脱氢酶（mt-IDH）蛋白的抑制剂，具有新型活性，可用于治疗细胞增殖障碍和癌症，其化学式为：其中A、U、W1、W2、W3、R1-R6和R9如本文所述。
• Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours
  作者：Valérie Weber、Lucie Arnaud、Sladjana Dukic-Stefanovic、Barbara Wenzel、Valérie Roux、Jean-Michel Chezal、Thu-Hang Lai、Rodrigo Teodoro、Klaus Kopka、Elisabeth Miot-Noirault、Winnie Deuther-Conrad、Aurélie Maisonial-Besset

  DOI：10.3390/molecules27123766

  日期：——

  Isocitrate dehydrogenases (IDHs) are metabolic enzymes commonly mutated in human cancers (glioma, acute myeloid leukaemia, chondrosarcoma, and intrahepatic cholangiocarcinoma). These mutated variants of IDH (mIDH) acquire a neomorphic activity, namely, conversion of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate involved in tumourigenesis. Thus, mIDHs have emerged as highly promising therapeutic targets, and several mIDH specific inhibitors have been developed. However, the evaluation of mIDH status, currently performed by biopsy, is essential for patient stratification and thus treatment and follow-up. We report herein the development of new radioiodinated and radiofluorinated analogues of olutasidenib (FT-2102) as tools for noninvasive single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging of mIDH1 up- and dysregulation in tumours. Nonradiolabelled derivatives 2 and 3 halogenated at position 6 of the quinolinone scaffold were synthesised and tested in vitro for their inhibitory potencies and selectivities in comparison with the lead compound FT-2102. Using a common organotin precursor, (S)-[125I]2 and (S)-[18F]3 were efficiently synthesised by radio-iododemetallation and copper-mediated radiofluorination, respectively. Both radiotracers were stable at room temperature in saline or DPBS solution and at 37 °C in mouse serum, allowing future planning of their in vitro and in vivo evaluations in glioma and chondrosarcoma models.

  异柠檬酸脱氢酶(IDHs)是常见突变的代谢酶，在人类肿瘤(如胶质瘤、急性髓性白血病、软骨肉瘤和肝内胆管癌)中突变。这些突变的IDH(mIDH)获得了新异构活性，即将α-酮戊二酸转化为参与肿瘤发生的致癌代谢物D-2-羟基戊二酸。因此，mIDH已成为极具前途的治疗靶点，已开发出多种mIDH特异性抑制剂。然而，目前通过活检评估mIDH状态对于患者分层、治疗和随访至关重要。我们在此报告了新型放射性碘化和放射性氟化物类似物的开发，作为非侵入性单光子发射计算机断层扫描(SPECT)或正电子发射断层扫描(PET)成像mIDH1在肿瘤中的上调和失调的工具。在萘酮骨架的6位卤代物基团上合成了非放射性衍生物2和3，并与引物化合物FT-2102进行比较，测试了它们的体外抑制效力和选择性。使用共同的有机锡前体，通过放射碘去金属化和铜介导的放射氟化反应，高效地合成了(S)-[125I]2和(S)-[18F]3。这两种放射性示踪剂在生理盐水或DPBS溶液中室温下和37℃的小鼠血清中稳定，允许未来计划在胶质瘤和软骨肉瘤模型中进行它们的体外和体内评价。
• Pyridin-2(1H)-one quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
  申请人：FORMA Therapeutics, Inc.

  公开号：US10414752B2

  公开（公告）日：2019-09-17

  The application relates to an inhibitor of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula (I-13):

  本申请涉及一种具有新变态活性的突变型异柠檬酸脱氢酶（mt-IDH）蛋白抑制剂，可用于治疗细胞增殖障碍和癌症，其分子式为 (I-13)：
• Solid forms of ((S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
  申请人：FORMA Therapeutics, Inc.

  公开号：US10959994B2

  公开（公告）日：2021-03-30

  The present disclosure reports solid forms of ((S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile.

  本公开报告了((S)-5-((1-(6-氯-2-氧代-1,2-二氢喹啉-3-基)乙基)氨基)-1-甲基-6-氧代-1,6-二氢吡啶-2-甲腈的固体形式。