2-甲基-2-丙基[1-(4-氟苯基)-1-氧代-2-丙基]氨基甲酸酯 | 211242-48-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-甲基-2-丙基[1-(4-氟苯基)-1-氧代-2-丙基]氨基甲酸酯
• 英文名称: 2-N-tert-butoxycarbonylamino-1-(4-fluorophenyl)-1-propanone
• 英文别名: tert-butyl (1-(4-fluorophenyl)-1-oxopropan-2-yl)carbamate；tert-butyl [1-(4-fluorophenyl)-1-oxopropan-2-yl]carbamate；tert-butyl N-[1-(4-fluorophenyl)-1-oxopropan-2-yl]carbamate
• CAS: 211242-48-7
• 化学式: C₁₄H₁₈FNO₃
• 分子量: 267.3
• InChiKey: OZFLADPELOCPRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基[1-(4-氟苯基)-1-氧代-2-丙基]氨基甲酸酯 在 盐酸 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 2-amino-1-(4-fluorophenyl)propan-1-ol
  参考文献：
  名称：

  Discovery of 3,5-Diphenyl-4-methyl-1,3-oxazolidin-2-ones as Novel, Potent, and Orally Available Δ-5 Desaturase (D5D) Inhibitors

  摘要：

  The discovery and optimization of Delta-5 desaturase (D5D) inhibitors are described. Investigation of the 1,3-oxazolidin-2-one scaffold was inspired by a pharmacophore model constructed from the common features of several hit compounds, resulting in the identification of 3,5-diphenyl-1,3-oxazolidin-2-one Sh as a novel lead showing potent in vitro activity. Subsequent optimization focused on the modification of two metabolic sites, which provided (4S,5S)-5i, a derivative with improved metabolic stability. Moreover, adding a substituent into the upper phenyl moiety further enhanced the intrinsic activity, which led to the discovery of 5-[(4S,5S)-5-(4fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzene-1,3-clicarbonitrile (4S,5S)-5n, endowed with excellent DSD binding affinity, cellular activity, and high oral bioavailability in a mouse. It exhibited robust in vivo hepatic arachidonic acid/dihomo-gamma-linolenic acid ratio reduction (a target engagement marker) in an atherosclerosis mouse model. Finally, an asymmetric synthetic procedure for this compound was established.

  DOI：

  10.1021/acs.jmedchem.7b01210
• 作为产物：
  描述：

  4'-氟苯丙酮 在 盐酸 、 sodium azide 、 溴 、 三乙胺 、 亚磷酸三乙酯 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 5.0h， 生成 2-甲基-2-丙基[1-(4-氟苯基)-1-氧代-2-丙基]氨基甲酸酯
  参考文献：
  名称：

  N.C.A.18F-labelled norephedrine derivatives via α-aminopropiophenones

  摘要：

  N-protected 2-anlino-1-([F-18]fluorophenyl)-1-propanones are interesting fluorine-18 labelled intermediates to synthesize potential PET-tracers for mapping the adrenergic nervous system of the heart. Several N-protected alpha -aminoalkylarylketones were prepared to examine the direct nucleophilic n.c.a. F-18-fluorination of these carbonyl activated precursors. The influence of different protecting groups, the kind of leaving group and the stereoselective reduction of the keto function have been investigated in order to optimize the radiotracer production. It was shown that the F-18-substitution of the para-trimethylammonium group, e.g. of N-dibenzylated propiophenone, leads to radiochemical yields of up to 60%. The stereoselective reduction of the carbonyl function with formation of the n.c.a. erythro 2-N,N-dibenzylamino-1-(4-[F-18]fluorophenyl)-1-propanol was performed using BH3. THF. The diastereomeric excess was about 80%. Hydrogenolytical debenzylation was achieved with ammonium formiate in presence of palladium on charcoal to give the 4-[F-18]fluoronorephedrine with a radiochemical yield of 15-20% within a total time of 60 min.

  DOI：

  10.1002/1099-1344(200012)43:14<1345::aid-jlcr424>3.0.co;2-n

文献信息

• [EN] METALLOENZYME INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE MÉTALLOENZYMES
  申请人：VPS 3 INC

  公开号：WO2018165520A1

  公开（公告）日：2018-09-13

  Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.

  提供具有HDAC6调节活性的化合物，以及通过HDAC6介导的治疗疾病、疾病或症状的方法。
• Metalloenzyme inhibitor compounds
  申请人：Selenity Therapeutics (Bermuda), Ltd.

  公开号：US10357493B2

  公开（公告）日：2019-07-23

  Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.

  本文提供了具有 HDAC6 调节活性的化合物，以及治疗由 HDAC6 介导的疾病、失调或症状的方法。
• METALLOENZYME INHIBITOR COMPOUNDS
  申请人：Viiamet Pharmaceuticals Holdings, LLC

  公开号：US20200171028A1

  公开（公告）日：2020-06-04

  Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.
• Discovery of 3,5-Diphenyl-4-methyl-1,3-oxazolidin-2-ones as Novel, Potent, and Orally Available Δ-5 Desaturase (D5D) Inhibitors
  作者：Jun Fujimoto、Rei Okamoto、Naoyoshi Noguchi、Ryoma Hara、Shinichi Masada、Tetsuji Kawamoto、Hiroki Nagase、Yumiko Okano Tamura、Mitsuaki Imanishi、Shuichi Takagahara、Kazuki Kubo、Kimio Tohyama、Koichi Iida、Tomohiro Andou、Ikuo Miyahisa、Junji Matsui、Ryouta Hayashi、Tsuyoshi Maekawa、Nobuyuki Matsunaga

  DOI：10.1021/acs.jmedchem.7b01210

  日期：2017.11.9

  The discovery and optimization of Delta-5 desaturase (D5D) inhibitors are described. Investigation of the 1,3-oxazolidin-2-one scaffold was inspired by a pharmacophore model constructed from the common features of several hit compounds, resulting in the identification of 3,5-diphenyl-1,3-oxazolidin-2-one Sh as a novel lead showing potent in vitro activity. Subsequent optimization focused on the modification of two metabolic sites, which provided (4S,5S)-5i, a derivative with improved metabolic stability. Moreover, adding a substituent into the upper phenyl moiety further enhanced the intrinsic activity, which led to the discovery of 5-[(4S,5S)-5-(4fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzene-1,3-clicarbonitrile (4S,5S)-5n, endowed with excellent DSD binding affinity, cellular activity, and high oral bioavailability in a mouse. It exhibited robust in vivo hepatic arachidonic acid/dihomo-gamma-linolenic acid ratio reduction (a target engagement marker) in an atherosclerosis mouse model. Finally, an asymmetric synthetic procedure for this compound was established.
• N.C.A.18F-labelled norephedrine derivatives via α-aminopropiophenones
  作者：J. Ermert、K. Hamacher、H. H. Coenen

  DOI：10.1002/1099-1344(200012)43:14<1345::aid-jlcr424>3.0.co;2-n

  日期：2000.12

  N-protected 2-anlino-1-([F-18]fluorophenyl)-1-propanones are interesting fluorine-18 labelled intermediates to synthesize potential PET-tracers for mapping the adrenergic nervous system of the heart. Several N-protected alpha -aminoalkylarylketones were prepared to examine the direct nucleophilic n.c.a. F-18-fluorination of these carbonyl activated precursors. The influence of different protecting groups, the kind of leaving group and the stereoselective reduction of the keto function have been investigated in order to optimize the radiotracer production. It was shown that the F-18-substitution of the para-trimethylammonium group, e.g. of N-dibenzylated propiophenone, leads to radiochemical yields of up to 60%. The stereoselective reduction of the carbonyl function with formation of the n.c.a. erythro 2-N,N-dibenzylamino-1-(4-[F-18]fluorophenyl)-1-propanol was performed using BH3. THF. The diastereomeric excess was about 80%. Hydrogenolytical debenzylation was achieved with ammonium formiate in presence of palladium on charcoal to give the 4-[F-18]fluoronorephedrine with a radiochemical yield of 15-20% within a total time of 60 min.