(4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone | 136564-80-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone
• 英文别名: (4R,5S)-4-methyl-5-phenyl-3-(4,4,4-trifluorobutanoyl)oxazolidin-2-one；(4R,5S)-4-methyl-3-(4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone；(4R,5S)-4-methyl-5-phenyl-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one
• CAS: 136564-80-2
• 化学式: C₁₄H₁₄F₃NO₃
• 分子量: 301.265
• InChiKey: FMZWFDPFAJPDDD-BXKDBHETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone 以55的产率得到(4R,5S)-3-((2R)-2-methyl-1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone
  参考文献：
  名称：

  A process for the preparation of 2(R)-methyl-4,4,4-trifluorobutylamine, intermediates, and a process for the preparation of a derivative thereof

  摘要：

  公开号：

  EP0489548B1
• 作为产物：
  描述：

  (4R,5S)-(+)-4-甲基-5-苯基-2-恶唑啉酮 、 4,4,4-三氟丁酰氯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 生成 (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone
  参考文献：
  名称：

  Carbamoyl derivatives

  摘要：

  本发明涉及一种新的氨基甲酰衍生物，其化学式为I，该衍生物在此处列出，能拮抗被称为白三烯的花生四烯酸代谢产物的药理作用，使其在需要拮抗这种作用的情况下非常有用，例如在白三烯参与的疾病治疗中，例如在过敏性或炎症性疾病的治疗中，或在内毒素性或创伤性休克症状的治疗中。该发明还提供了含有这些新衍生物的药物组合物，用于进行这种治疗的方法，以及用于制造这些新衍生物的方法和中间体。

  公开号：

  US05286740A1

文献信息

• [EN] BETA-TETRAZOLYL-PROPIONIC ACIDS AS METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] ACIDES BÊTA-TÉTRAZOLYLE-PROPIONIQUES UTILES EN TANT QU'INHIBITEURS DES MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015171474A1

  公开（公告）日：2015-11-12

  The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及公式I的化合物，这些化合物是金属β-内酰胺酶抑制剂，以及这些化合物的合成和与β-内酰胺类抗生素一起使用以克服抗性的用途。
• Chemical process for the preparation of 3-alkylated indole
  申请人：Imperial Chemical Industries PLC

  公开号：US05280125A1

  公开（公告）日：1994-01-18

  A process for the preparation of a 3-alkylated indole, which comprises: a) reacting a N-(2-nitrostyryl) enamine with an alkylating agent to afford an imine salt, b) optionally reacting the imine salt with water to afford a (2-nitrophenyl)acetaldehyde, and c) reacting the imine salt or the (2-nitrophenyl)acetaldehyde with a reducing agent capable of selectively reducing the nitro group, to afford the desired 3-alkylated indole.

  制备3-烷基吲哚的方法包括：a) 将N-(2-硝基苯乙烯基)烯胺与烷基化试剂反应，形成亚胺盐，b) 可选地将亚胺盐与水反应，形成(2-硝基苯基)乙醛，以及c) 将亚胺盐或(2-硝基苯基)乙醛与能够选择性还原硝基的还原剂反应，形成所需的3-烷基吲哚。
• Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4
  作者：Robert T. Jacobs、Peter R. Bernstein、Laura A. Cronk、Edward P. Vacek、Lisa F. Newcomb、David Aharony、Carl K. Buckner、Edward J. Kusner

  DOI：10.1021/jm00035a008

  日期：1994.4

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.
• A process for the preparation of a 3-alkylated indole, intermediates, and a process for the preparation of a derivative thereof
  申请人：ZENECA LIMITED

  公开号：EP0489547B1

  公开（公告）日：1998-07-29
• BETA-TETRAZOLYL-PROPIONIC ACIDS AS METALLO-BETA-LACTAMASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3139918A1

  公开（公告）日：2017-03-15