3-[(2S)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[(2S)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid
• 英文别名: 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(2-carboxylethyl)-1,3-thiazolidin-4-one；2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-(2-carboxyethyl)-1,3-thiazolidin-4-one；3-[2-(3,5-ditert-butyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid
• 化学式: C₂₀H₂₉NO₄S
• 分子量: 379.521
• InChiKey: UIMHPDNTBDMNOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[(2S)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid 在 sodium tetrahydroborate 、 锂硼氢 、 potassium carbonate 、 三乙胺 、 sodium iodide 、 calcium chloride 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 21.25h， 生成 (-)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-[3-[N-methyl-N-[2-[3,4-(methylenedioxy)phenoxy]ethyl]amino]propyl]-1,3-thiazolidin-4-one hydrogen fumarate salt
  参考文献：
  名称：

  Practical Synthesis of Novel Cardioprotective Drug, CP-060S

  摘要：

  A practical synthesis of a novel cardioprotective drug, CP-060S, is described. Key intermediate (S)-7, a chiral carboxylic acid, was prepared from 3,5-di-tert-butyl-4-hydroxybenzaldehyde 2 by employing thiazolidinone cyclocondensation followed by selective crystallization from a diastereomeric salt mixture which was prepared by treating racemic 7 with (S)-(-)-N-benzyl-alpha -methylbenzylamine 11. Racemization of the (R)-7-rich mixture, obtained from the mother liquid, by treatment with NaOH solution and subsequent resolution gave a second crop of (S) 7. Resolving agent 11 was efficiently recovered from the resolution process and pure enough for recycling use. Chiral acid (S)-7 was converted to the corresponding methyl ester (S)-1.4, which was reduced with NaBH4-CaCl2 to give alcohol intermediate (S)-4. Subsequent mesylation, amination, and salt formation with fumaric acid afforded CP-060S as pure enantiomer (99.8% ee) without any column chromatography.

  DOI：

  10.1021/op000096h
• 作为产物：
  描述：

  3-[(S)-2-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-4-oxo-thiazolidin-3-yl]-propionic acid 在 氘氧化钠 、 diclazuril 作用下， 以 氘代甲醇 、 重水 为溶剂， 反应 2.0h， 以77 mg的产率得到3-[(2S)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid
  参考文献：
  名称：

  Mechanistic Studies on Racemization of Chiral 2-Arylthiazolidinons

  摘要：

  Mechanistic studies on racemization of chiral 3-[(2S)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid is described. This racemization is triggered by deprotonation of phenolic hydroxyl group. We propose that the racemization proceeds via a novel mechanism involving ring opening-closure equilibrium of the thiazolidinone ring.

  DOI：

  10.3987/com-01-9175

文献信息

• BENZENE DERIVATIVE USEFUL FOR ISCHEMIC DISEASES
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP0705816A1

  公开（公告）日：1996-04-10

  Compounds represented by formula (I): wherein, for example, R₁, R₂, R₃, and R₄ each represents a hydrogen atom; R₆ and R₇ each represent a substituted or unsubstituted lower alkyl group; A represents a group represented by formula (II): wherein R₅ represents, for example, a hydrogen atom; and n represents an integer of 2 to 6, or a possible stereoisomer or optical isomer thereof and a pharmaceutically acceptable salt thereof. The compounds represented by formula (I) have an inhibitory action on calcium overload in addition to a vasorelaxing activity (calcium antagonism) and an inhibitory action on lipid peroxidation and are useful as a preventive or treating agent for ischemic diseases and a hypertension.

  式 (I) 所代表的化合物： 其中，R₁、R₂、R₃ 和 R₄ 各自代表氢原子；R₆ 和 R₇ 各自代表取代或未取代的低级烷基；A 代表式 (II) 所代表的基团： 其中 R₅ 代表例如氢原子；n 代表 2 至 6 的整数，或其可能的立体异构体或光学异构体及其药学上可接受的盐。式 (I) 所代表的化合物除了具有血管舒张活性（钙离子拮抗作用）和脂质过氧化抑制作用外，还具有抑制钙超载的作用，可用作缺血性疾病和高血压的预防或治疗药物。
• REMEDY FOR ISCHEMIC DISEASES
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0799614A1

  公开（公告）日：1997-10-08

  A compound represented by general formula (I), possible stereoisomer and optical isomer thereof, and pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 represent each hydrogen, etc.; R6 and R7 represent each optionally substituted lower alkyl; A represents a group of general formula (II) (wherein R5 represents hydrogen, etc.); and n is an integer of from 2 to 6. These compounds can suppress the formation of active oxygen and an increase in intracellular calcium and thus are useful as a remedy for ischemic diseases.

  通式（I）代表的化合物、其可能的立体异构体和光学异构体及其药学上可接受的盐，其中 R1、R2、R3 和 R4 分别代表氢等；R6 和 R7 分别代表任选取代的低级烷基；A 代表通式（II）的基团（其中 R5 代表氢等）；n 为 2 至 6 的整数。这些化合物可抑制活性氧的形成和细胞内钙的增加，因此可用于治疗缺血性疾病。
• US5998452
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• EP799614
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• US05998452
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  公开（公告）日：——