2-hydroxy-2-trifluoromethylbutanoic acid | 72114-82-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-hydroxy-2-trifluoromethylbutanoic acid
• 英文别名: 2-hydroxy-2-trifluoromethylbutyric acid；2-Hydroxy-2-(trifluoromethyl)butyric acid；2-hydroxy-2-(trifluoromethyl)butanoic acid
• CAS: 72114-82-0
• 化学式: C₅H₇F₃O₃
• mdl: MFCD00190638
• 分子量: 172.104
• InChiKey: HPUAIGRGCRIKGO-UHFFFAOYSA-N

物化性质

• 沸点：
  257.5±35.0 °C(Predicted)
• 密度：
  1.438±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 安全说明：
  SR26

反应信息

• 作为反应物：
  描述：

  2-hydroxy-2-trifluoromethylbutanoic acid 在 甲醇 、 硫酸 作用下， 反应 4.0h， 生成 (S)-2-hydroxy-2-(trifluoromethyl)butyric acid methyl ester
  参考文献：
  名称：

  The synthesis of (R)- and (S)-α-trifluoromethyl-α-hydroxycarboxylic acids via enzymatic resolutions

  摘要：

  Kinetic resolution of 1,1,1-trifluoro-2-alkanone cyanohydrin acyl derivatives with Candida rugosa lipase afforded the remaining (R)-enantiomer in high selectivity (E from 30 to >200). Candida rugosa lipases from several suppliers were compared and found to differ remarkably in their selectivity. The (R)-enantiomer was hydrolyzed in one step to yield optically pure (R)-alpha-trifluoromethyl-alpha-hydroxycarboxylic acids in excellent yield. The (S)-acids were obtained in good e.e. by subtilisin-catalyzed resolution of the corresponding racemic esters followed by chemical hydrolysis of the remaining (S)-esters. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00017-8
• 作为产物：
  描述：

  2-hydroxy-2-(trifluoromethyl)butyric acid methyl ester 在 盐酸 作用下， 反应 10.0h， 以76%的产率得到2-hydroxy-2-trifluoromethylbutanoic acid
  参考文献：
  名称：

  Soloshonok, V. A.; Gerus, I. I.; Yagupol'skii, Yu. L., Journal of Organic Chemistry USSR (English Translation), 1987, vol. 23, # 7, p. 1298 - 1303

  摘要：

  DOI：

文献信息

• Secondary Amides of (<i>R</i>)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionic Acid as Inhibitors of Pyruvate Dehydrogenase Kinase
  作者：Thomas D. Aicher、Robert C. Anderson、Jiaping Gao、Suraj S. Shetty、Gary M. Coppola、James L. Stanton、Douglas C. Knorr、Donald M. Sperbeck、Leonard J. Brand、Christine C. Vinluan、Emma L. Kaplan、Carol J. Dragland、Hollis C. Tomaselli、Amin Islam、Robert J. Lozito、Xilin Liu、Wieslawa M. Maniara、William S. Fillers、Dominick DelGrande、R. Eric Walter、William R. Mann

  DOI：10.1021/jm990358+

  日期：2000.1.1

  6-tetrahydropyridine)thiourea, SDZ048-619 (1), is a modest inhibitor (IC(50) = 180 microM) of pyruvate dehydrogenase kinase (PDHK). In an optimization of the N-methylcarbothioamide moiety of 1, it was discovered that amides with a small acyl group, in particular appropriately substituted amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, are inhibitors of PDHK. Utilizing this acyl moiety, herein is

  N'-甲基-N-（4-叔丁基-1,2,5,6-四氢吡啶）硫脲SDZ048-619（1）是丙酮酸脱氢酶激酶的适度抑制剂（IC（50）= 180 microM） （PDHK）。在最优化1的N-甲基碳硫酰胺部分时，发现具有小的酰基的酰胺，特别是（R）-3,3,3-三氟-2-羟基-2-甲基-2-丙酸的适当取代的酰胺，是PDHK的抑制剂。本文报道了利用该酰基部分的原理，其导致一系列酰化哌嗪衍生物的优化。哌嗪在2和5位上的甲基取代（具有S和R绝对立体化学）显着提高了前导化合物的效价（> 1,000倍）。当哌嗪的4位被电子贫乏的苯甲酰基部分取代时，该系列化合物的口服生物利用度良好且最佳（通过AUC测定）。（+）-1-N- [2,5-（S，R）-二甲基-4-N-（4-氰基苯甲酰基）哌嗪]-（R）-3,3，3-三氟-2-羟基-2 -甲基丙酰胺（14e）抑制PDHK在主要酶促测定中的IC（50）为16 +/-
• The Discovery of Setileuton, a Potent and Selective 5-Lipoxygenase Inhibitor
  作者：Yves Ducharme、Marc Blouin、Christine Brideau、Anne Châteauneuf、Yves Gareau、Erich L. Grimm、Hélène Juteau、Sébastien Laliberté、Bruce MacKay、Frédéric Massé、Marc Ouellet、Myriam Salem、Angela Styhler、Richard W. Friesen

  DOI：10.1021/ml100029k

  日期：2010.7.8

  The discovery of novel and selective inhibitors of human 5-lipoxygenase (5-LO) is described. These compounds are potent, orally bioavailable, and active at inhibiting leukotriene biosynthesis in vivo in a dog PK/PD model. A major focus of the optimization process was to reduce affinity for the human ether-a-go-go gene potassium channel while preserving inhibitory potency on 5-LO. These efforts led

  描述了人类 5-脂肪氧化酶 (5-LO) 的新型选择性抑制剂的发现。这些化合物是有效的、口服生物可利用的，并且在狗 PK/PD 模型中在体内抑制白三烯生物合成方面具有活性。优化过程的一个主要焦点是降低对人类 ether-a-go-go 基因钾通道的亲和力，同时保持对 5-LO 的抑制效力。这些努力导致了抑制剂 ( S ) -16（MK-0633，setileuton）的鉴定，该化合物被选为临床开发用于治疗呼吸系统疾病的化合物。
• Chemical compounds and their use to elevate pyruvate dehydrogenase activity
  申请人：AstraZeneca AB

  公开号：US06369273B1

  公开（公告）日：2002-04-09

  The use of a compound of the formula (I): wherein: ring C is phenyl or carbon-linked heteroaryl selected from pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl; and wherein said phenyl or heteroaryl is substituted as defined herein; A—B is selected from NHCO, OCH2, SCH2, NHCH2, trans-vinylene, and ethynylene; R1 is linked to ring C at a carbon ortho to the position of A—B attachment and is defined herein; n is 1 or 2; R2 and R3 are alkyl, haloalkyl or together from cycloalkyl or halocycloalkyl as defined herein; in the manufacture of a medicament for use in the elevation of PDH activity in warm-blooded animals such as humans is described. Salts and esters of compounds of formula (I) are also described.

  该化合物的使用公式（I）：其中：环C为苯基或碳链杂环芳基，选择自吡啶基、吡嗪基、嘧啶基和吡啶并吡嗪基；所述苯基或杂环芳基如本文所定义被取代；A—B选择自NHCO、OCH2、SCH2、NHCH2、反式乙烯基和乙炔基；R1与环C连接在与A—B连接位置的邻位碳上，如本文所定义；n为1或2；R2和R3为烷基、卤代烷基或如本文所定义的环烷基或卤代环烷基；描述了制造用于提高温血动物（如人类）PDH活性的药物。还描述了公式（I）化合物的盐和酯。
• SOLOSHONOK, V. A.;GERUS, I. I.;YAGUPOLSKIJ, YU. L.;KUXAR, V. P., ZH. ORGAN. XIMII, 23,(1987) N 7, 1441-1447
  作者：SOLOSHONOK, V. A.、GERUS, I. I.、YAGUPOLSKIJ, YU. L.、KUXAR, V. P.

  DOI：——

  日期：——
• Soloshonok, V. A.; Gerus, I. I.; Yagupol'skii, Yu. L., Journal of Organic Chemistry USSR (English Translation), 1987, vol. 23, # 7, p. 1298 - 1303
  作者：Soloshonok, V. A.、Gerus, I. I.、Yagupol'skii, Yu. L.、Kukhar', V. P.

  DOI：——

  日期：——