(4S)-3-[(4-fluorophenyl)acetyl]-4-isopropyl-1,3-oxazolidin-2-one | 762297-72-3

• 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: (4S)-3-[(4-fluorophenyl)acetyl]-4-isopropyl-1,3-oxazolidin-2-one
• 英文别名: (S)-3-(2-(4-fluorophenyl)acetyl)-4-isopropyloxazolidin-2-one；(4S)-3-[(4-fluorophenyl)acetyl]4-isopropyl-1,3-oxazolidin-2-one；(4S)-3-[2-(4-fluorophenyl)acetyl]-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 762297-72-3
• 化学式: C₁₄H₁₆FNO₃
• 分子量: 265.284
• InChiKey: ZWLNCTBDMYQMFG-GFCCVEGCSA-N

物化性质

• 沸点：
  411.2±28.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 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：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-3-[(4-fluorophenyl)acetyl]-4-isopropyl-1,3-oxazolidin-2-one 在 lithium hydroxide 、 双氧水 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 (2S)-2-(4-氟苯基)丙酸
  参考文献：
  名称：

  Synthesis and SAR Investigations for Novel Melanin-Concentrating Hormone 1 Receptor (MCH₁) Antagonists Part 1. The Discovery of Arylacetamides as Viable Replacements for the Dihydropyrimidinone Moiety of an HTS Hit

  摘要：

  Melanin-concentrating hormone (MCH) is involved in the regulation of feeding, water balance, energy metabolism, general arousal and attention state, memory, cognitive functions, and psychiatric disorders. Herein, two new chemical series exemplified by N-[5-(1-{3-[2,2-bis-(4-fluoro-phenyl)-acetylamino]-propyl}-piperidin-4-yl)-2,4-difluoro-phenyl]-isobutyramide (SNAP 102739, 5m) and N-[3-(l-{3-[(S)-2-(4-fluorophenyl)-propionylamino]-propyl}-piperidin-4-yl)-4-methylphenyl]-isobutyramide ((S)-6b) are reported. These compounds were designed to improve the pharmacokinetic properties of the high-throughput screening lead compound 1 (SNAP 7941). The MCH, receptor antagonists 5m and (S)-6b show reasonable pharmacokinetic profiles (rat bioavailability = 48 and 81%, respectively). Compounds 5m and (S)-6b demonstrated the inhibition of a centrally administered MCH-evoked drinking effect, and compound 5m exhibited oral in vivo efficacy in the rat social interaction model of anxiety, with a minimum effective dose = 0.3 mg/kg.

  DOI：

  10.1021/jm060381c
• 作为产物：
  描述：

  (S)-4-异丙基-2-唑烷酮 、 对氟苯乙酰氯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 以69%的产率得到(4S)-3-[(4-fluorophenyl)acetyl]-4-isopropyl-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Synthesis and SAR Investigations for Novel Melanin-Concentrating Hormone 1 Receptor (MCH₁) Antagonists Part 1. The Discovery of Arylacetamides as Viable Replacements for the Dihydropyrimidinone Moiety of an HTS Hit

  摘要：

  Melanin-concentrating hormone (MCH) is involved in the regulation of feeding, water balance, energy metabolism, general arousal and attention state, memory, cognitive functions, and psychiatric disorders. Herein, two new chemical series exemplified by N-[5-(1-{3-[2,2-bis-(4-fluoro-phenyl)-acetylamino]-propyl}-piperidin-4-yl)-2,4-difluoro-phenyl]-isobutyramide (SNAP 102739, 5m) and N-[3-(l-{3-[(S)-2-(4-fluorophenyl)-propionylamino]-propyl}-piperidin-4-yl)-4-methylphenyl]-isobutyramide ((S)-6b) are reported. These compounds were designed to improve the pharmacokinetic properties of the high-throughput screening lead compound 1 (SNAP 7941). The MCH, receptor antagonists 5m and (S)-6b show reasonable pharmacokinetic profiles (rat bioavailability = 48 and 81%, respectively). Compounds 5m and (S)-6b demonstrated the inhibition of a centrally administered MCH-evoked drinking effect, and compound 5m exhibited oral in vivo efficacy in the rat social interaction model of anxiety, with a minimum effective dose = 0.3 mg/kg.

  DOI：

  10.1021/jm060381c

文献信息

• Substituted alkyl amido piperidines
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US20040186103A1

  公开（公告）日：2004-09-23

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety.

  这项发明涉及选择性拮抗黑色素浓缩激素-1（MCH1）受体的化合物。该发明提供了一种包括该发明化合物的治疗有效量和药学上可接受的载体的药物组合物。该发明提供了一种由结合本发明化合物的治疗有效量和药学上可接受的载体制成的药物组合物。该发明还提供了一种制备药物组合物的方法，包括结合本发明化合物的治疗有效量和药学上可接受的载体。该发明还提供了一种减少受试者体重的方法，包括向受试者施用本发明化合物的有效量以减少受试者的体重。该发明还提供了一种治疗患有抑郁症和/或焦虑症的受试者的方法，包括向受试者施用本发明化合物的有效量以治疗受试者的抑郁症和/或焦虑症。
• [EN] INDANE DERIVATIVES AS MGLUR7 MODULATORS<br/>[FR] DÉRIVÉS D'INDANE UTILISÉS COMME MODULATEURS DE MGLUR7
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017131221A1

  公开（公告）日：2017-08-03

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4a and R4b are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds of formula (I) are mGluR7 modulators.

  本发明提供了式（I）的化合物及其药学上可接受的盐，其中R1、R2、R3、R4a和R4b如规范中定义，其制备方法，含有它们的药物组合物以及它们在治疗中的用途。式（I）的化合物是mGluR7调节剂。
• Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain
  作者：Guan-Sheng Jiao、Seongjin Kim、Mahtab Moayeri、Devorah Crown、April Thai、Lynne Cregar-Hernandez、Linda McKasson、Banumathi Sankaran、Axel Lehrer、Teri Wong、Lisa Johns、Stephen A. Margosiak、Stephen H. Leppla、Alan T. Johnson

  DOI：10.1016/j.bmcl.2012.01.095

  日期：2012.3

  Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography. (C) 2012 Elsevier Ltd. All rights reserved.
• SUBSTITUTED ALKYL AMIDO PIPERIDINES
  申请人：H. LUNDBECK A/S

  公开号：EP1590326A2

  公开（公告）日：2005-11-02
• EP1590326A4
  申请人：——

  公开号：EP1590326A4

  公开（公告）日：2008-04-30