(4S)-4-(Propan-2-yl)-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one

• 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: (4S)-4-(Propan-2-yl)-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one
• 英文别名: (4S)-4-propan-2-yl-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one
• 化学式: C₁₀H₁₄F₃NO₃
• 分子量: 253.221
• InChiKey: DAGPYFHPIILCIF-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  tert-butyl 5,5,5-trifluoropentanoate 、 (4S)-4-(Propan-2-yl)-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one 在 lithium chloride 、 lithium diisopropyl amide 、 copper(II) 2-ethylhexanoate 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 1.16h， 以28%的产率得到tert-Butyl (3R)-5,5,5-trifluoro-3-(((4S)-2-oxo-4-(propan-2-yl)-1,3-oxazolidin-3-yl)carbonyl)-2-(3,3,3-trifluoropropyl)pentanoate
  参考文献：
  名称：

  合成 2,3-二取代琥珀酸酯中对映和非对映控制的实用方法：泛缺口抑制剂 BMS-906024 的合成

  摘要：

  氧化分子间烯醇杂偶联反应用于合成抗 2,3-二取代琥珀酸单和差异保护的二酯。讨论了获取所有非对映异构体的战术方法。该方法用于合成一种有效的抗癌剂 BMS-906024。

  DOI：

  10.1055/s-0035-1561636
• 作为产物：
  描述：

  4,4,4-三氟丁酰氯 、 (S)-4-异丙基-2-唑烷酮 在 正丁基锂 作用下， 生成 (4S)-4-(Propan-2-yl)-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00035a008

文献信息

• BISFLUOROALKYL-1,4-BENZODIAZEPINONE COMPOUNDS
  申请人：GAVAI ASHVINIKUMAR V.

  公开号：US20120245151A1

  公开（公告）日：2012-09-27

  Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R 1 is —CH 2 CF 3 or —CH 2 CH 2 CF 3 ; R 2 is —CH 2 CF 3 , —CH 2 CH 2 CF 3 , or —CH 2 CH 2 CH 2 CF 3 ; R 3 is H or —CH 3 ; each R a is independently F, Cl, —CN, —OCH 3 , and/or —NHCH 2 CH 2 OCH 3 ; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  揭示了Formula (I)的化合物或其前药；其中：R1为—CH2CF3或—CH2CH2CF3；R2为—CH2CF3，—CH2CH2CF3，或—CH2CH2CH2CF3；R3为H或—CH3；每个Rai独立地为F，Cl，—CN，—OCH3，和/或—NHCH2CH2OCH3；z为零，1或2。还揭示了使用这些化合物来抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或障碍方面是有用的，比如癌症。
• [EN] BIS(FLUOROALKYL)-1,4-BENZODIAZEPINONE COMPOUNDS<br/>[FR] COMPOSÉS BIS(FLUOROALKYL)-1,4-BENZODIAZÉPINONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012129353A1

  公开（公告）日：2012-09-27

  Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R1 is CH2CF3 or CH2CH2CF3; R2 is CH2CF3, CH2CH2CF3, or CH2CH2CH2CF3; R3 is H or CH3; each Ra is independently F, Cl, -CN, -OCH3, and/or NHCH2CH2OCH3; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  本文披露了式（I）的化合物或其前药，其中：R1为CH2CF3或CH2CH2CF3；R2为CH2CF3，CH2CH2CF3或CH2CH2CH2CF3；R3为H或CH3；每个Ra独立地为F，Cl，-CN，-OCH3和/或NHCH2CH2OCH3；z为零，1或2。还披露了使用这些化合物抑制Notch受体的方法和包含这些化合物的药物组合物。这些化合物在多种治疗领域中用于治疗、预防或减缓疾病或障碍的进展，例如癌症。
• BIS(FLUOROALKYL)-1,4-BENZODIAZEPINONE COMPOUNDS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20140357605A1

  公开（公告）日：2014-12-04

  Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R 1 is —CH 2 CF 3 or —CH 2 CH 2 CF 3 ; R 2 is —CH 2 CF 3 , —CH 2 CH 2 CF 3 , or —CH 2 CH 2 CH 2 CF 3 ; R 3 is H or —CH 3 ; each R a is independently F, Cl, —CN, —OCH 3 , and/or —NHCH 2 CH 2 OCH 3 ; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  本发明公开了式（I）的化合物或其前药；其中：R1是—CH2CF3或—CH2CH2CF3；R2是—CH2CF3，—CH2CH2CF3或—CH2CH2CH2CF3；R3是H或—CH3；每个Ra独立地是F，Cl，—CN，—OCH3和/或—NHCH2CH2OCH3；z为零，1或2。本发明还公开了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物在治疗癌症等多种治疗领域中用于治疗、预防或减缓疾病或障碍的进展。
• Bisfluoroalkyl-1,4-benzodiazepinone compounds
  申请人：Bristol-Myers Squibb Company

  公开号：US08822454B2

  公开（公告）日：2014-09-02

  Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R1 is —CH2CF3 or —CH2CH2CF3; R2 is —CH2CF3, —CH2CH2CF3, or —CH2CH2CH2CF3; R3 is H or —CH3; each Ra is independently F, Cl, —CN, —OCH3, and/or —NHCH2CH2OCH3; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  本发明涉及式（I）化合物或其前药；其中：R1为—CH2CF3或—CH2CH2CF3；R2为—CH2CF3，—CH2CH2CF3或—CH2CH2CH2CF3；R3为H或—CH3；每个Ra独立地为F、Cl、—CN、—OCH3和/或—NHCH2CH2OCH3；且z为零、1或2。本发明还涉及使用这些化合物抑制Notch受体的方法，以及包含这些化合物的制药组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病进展方面是有用的，例如癌症。
• US8629136B2
  申请人：——

  公开号：US8629136B2

  公开（公告）日：2014-01-14