2,2-difluoroglutaric anhydride | 79361-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 2,2-difluoroglutaric anhydride
• 英文别名: 3,3-difluorodihydro-2H-pyran-2,6(3H)-dione；3,3-difluorooxane-2,6-dione
• CAS: 79361-03-8
• 化学式: C₅H₄F₂O₃
• 分子量: 150.082
• InChiKey: JICFSEVPEYNTTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2-difluoroglutaric anhydride 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 5-(4-(4-(8-bromoquinoxalin-2-yl)-1H-pyrazol-1-yl)piperidin-1-yl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoro-5-oxopentanamide
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS OF TREATING CANCERS
  [FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE CANCERS

  摘要：

  本公开涉及GSPT1降解剂化合物（例如小分子化合物），包含一种或多种该化合物的组合物，以及使用该化合物治疗特定疾病的方法，适用于需要该治疗的个体。本公开还涉及识别这种化合物的方法。

  公开号：

  WO2022073469A1
• 作为产物：
  描述：

  2,2-二氟戊二酸 在 resulting solution 作用下， 以 乙酸酐 为溶剂， 反应 2.0h， 生成 2,2-difluoroglutaric anhydride
  参考文献：
  名称：

  Chemical synthesis

  摘要：

  以下位置中任意一个或多个被氟取代的前列腺素和前列环素化合物：4,4；7,7；10,10；和5。

  公开号：

  US04456768A1

文献信息

• Certain fluorine substituted PGI.sub.2 compounds
  申请人：The University of Chicago

  公开号：US04324730A1

  公开（公告）日：1982-04-13

  Prostaglandin and prostacyclin compounds which are fluorine substituted in any one or more of the following positions, 4,4; 7,7; 10,10; and 5.

  以下位置中任意一个或多个含氟取代的前列腺素和前列环素化合物，4,4；7,7；10,10；以及5。
• Synthesis of 2-aryl-3-hydroxymethyl-5,5-difluoropiperidines
  作者：Matthias Moens、Guido Verniest、Matthias De Schrijver、Peter ten Holte、Jan-Willem Thuring、Frederik Deroose、Norbert De Kimpe

  DOI：10.1016/j.tet.2012.08.049

  日期：2012.11

  A strategy toward the synthesis of functionalized 5,5-difluoropiperidines, a class of compounds with potential as building block in medicinal chemistry, was developed. In a three-step procedure 2,2-difluoroglutaric anhydride was synthesized starting from ethyl bromodifluoroacetate. This key intermediate reacts fluently with various imines to yield 5,5-difluoropiperidinone carboxylic acids. Subsequent esterification of the obtained carboxylic acids enabled the isolation of trans-substituted 5,5difluoro-2-arylpiperidinone-3-carboxylates as the major isomers. Reduction of the difluorinated piperidinonecarboxylates using borane gave rise to new trans-2-aryl-1-benzyl-5,5-difluoro-3-hydroxymethylpiperidines in excellent yields. (C) 2012 Elsevier Ltd. All rights reserved.
• Neuromuscular Blocking Activity and Therapeutic Potential of Mixed-Tetrahydroisoquinolinium Halofumarates and Halosuccinates in Rhesus Monkeys
  作者：Eric E. Boros、Vicente Samano、John A. Ray、James B. Thompson、David K. Jung、Istvan Kaldor、Cecilia S. Koble、Michael T. Martin、Virgil L. Styles、Robert A. Mook、Paul L. Feldman、John J. Savarese、Matthew R. Belmont、Eric C. Bigham、G. Evan Boswell、Mir A. Hashim、Sanjay S. Patel、James C. Wisowaty、Gary D. Bowers、Caroline L. Moseley、John S. Walsh、Mindy J. Reese、Randy D. Rutkowske、Andrea M. Sefler、Timothy D. Spitzer

  DOI：10.1021/jm020574+

  日期：2003.6.1

  Structure-activity relationships in rhesus monkeys for a novel mixed-onium class of ultra-short-acting nondepolarizing tetrahydroisoquinolinium neuromuscular blockers (NMBs) are described. Bis-onium chlorofumarate 20a with (1R,2S)-benzyltetrahydroisoquinolinium groups was a potent lead compound (ED95 = 0.079 mg/kg) with an ultra-short duration of NMB effect (7.1 min) and a selectivity index (SI: defined as a ratio of the cardiovascular threshold dose to the ED95) similar to that of mivacurium (3). The mean threshold dose for cardiovascular effects with 20a was ca. 20 times its ED95 value (SI = 20). A novel mixed-onium analogue of 20a was prepared by replacing the benzyltetrahydroisoquinolinium group distal to the fumarate chlorine atom with a (1S,2R)-phenyltetrahydroisoquinolinium moiety. The resulting mixed-onium chlorofumarate 24a displayed good NMB potency (ED95 = 0.063 mg/kg), ultra-short duration of action (5.6 min) and an improved selectivity index (SI = 57). Several other mixed-onium derivatives containing octanedioate (25a; ED95 = 0.103 mg/kg), difluorosuccinate (27c; ED95 = 0.056 mg/kg), and fluorofumarate (28a; ED95 = 0.137 mg/kg) linkers were also potent, ultra-short-acting NMBs with good to excellent selectivity index values (SI = 37-96). Octanedioate 25a was longer acting at higher doses compared to difluorosuccinate 27c and chlorofumarate 24a. Durations of NMB effect following a 0.4 mg/kg bolus dose (100% block) of 25a, 27c, and 24a were 16.9, 13.0, and 10.0 min, respectively. Recovery time for mixed-onium chlorofumarate 24a following a 1 h continuous infusion at 10-20 mug/kg/min (95-100% block) was ca. 5 min which is similar to that observed following a 0.2 mg/kg bolus dose of this compound and indicates a lack of cummulative effects. Preliminary studies with chlorofumarate 24a in whole human blood revealed that mixed-onium thiazolidine 29 was the major metabolite and that plasma cholinesterases do not play the primary role in duration of NMB effect. The NMB properties of 24a in rhesus monkeys led to its clinical evaluation as a possible alternative to succinylcholine.