(R)-3-((2R,3S)-2-bromo-3-(4-methoxyphenyl)butanoyl)-4-phenyloxazolidin-2-one | 154006-51-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-3-((2R,3S)-2-bromo-3-(4-methoxyphenyl)butanoyl)-4-phenyloxazolidin-2-one
• 英文别名: (4R)-3-[(2R,3S)-2-bromo-3-(4-methoxyphenyl)butanoyl]-4-phenyl-1,3-oxazolidin-2-one
• CAS: 154006-51-6
• 化学式: C₂₀H₂₀BrNO₄
• 分子量: 418.287
• InChiKey: DWRRMBAWCLVJED-DOPJRALCSA-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：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-3-((2R,3S)-2-bromo-3-(4-methoxyphenyl)butanoyl)-4-phenyloxazolidin-2-one 在 lithium hydroxide 、 双氧水 、 N,N,N',N'-四甲基胍叠氮化物 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 (2S,3S)-2-Azido-3-(4-methoxyphenyl)butyric acid
  参考文献：
  名称：

  发现有效的和选择性的基于苯丙氨酸的二肽基肽酶IV抑制剂。

  摘要：

  抗取代的β-甲基苯基丙氨酸衍生的酰胺已被证明是有效的DPP-IV抑制剂，对DPP8和DPP9均表现出优异的选择性。这些是迄今报道的最有效的缺乏亲电子阱的化合物。其中最有效的化合物是5-氧-1,2,4-氧二唑44，它是一种3 nM DPP-IV抑制剂。

  DOI：

  10.1016/j.bmcl.2005.03.055
• 作为产物：
  描述：

  (3(3R),4S)-3-<3-(4'-Methoxyphenyl)butanoyl>-4-phenyl-2-oxazolidinone 在 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 三氟甲磺酸二丁硼 、 双氧水 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 14.42h， 生成 (R)-3-((2R,3S)-2-bromo-3-(4-methoxyphenyl)butanoyl)-4-phenyloxazolidin-2-one
  参考文献：
  名称：

  Efficient method for the total asymmetric synthesis of the isomers of .beta.-methyltyrosine

  摘要：

  Alpha-Amino acids modified at the beta-carbon atom can provide topographical constraints when incorporated into a peptide. Such modifications can modulate the physical, chemical, and biological properties of the compound. In order to properly evaluate the effect of such modifications, large-scale asymmetric syntheses of the isomers are needed. A method for the stereoselective large-scale synthesis of an four stereoisomers of beta-methyltyrosine is described in this paper. The stereochemistry of both the alpha- and beta-stereocenters was set using 4-phenyl-2-oxazolidinone as a chiral auxiliary. The key reactions were an asymmetric Michael-like addition of an organocuprate to a chiral alpha,beta-unsaturated acyloxazolidinone (beta center) and subsequent stereoselective electrophilic bromination of the resulting product (alpha center). Conversion of the bromide to the azide, catalyzed hydrolysis to the azido acid with simultaneous recovery of the chiral auxiliary, reduction of the azide, and final deprotection of the phenol group afforded the desired amino acids. In general, the reactions were performed in yields over 80 %, and the isomers were obtained in enantiomeric purities of 98:2 to 99:1.

  DOI：

  10.1021/jo00078a042

文献信息

• [EN] UREA DERIVATIVE OR PHARMACOLOGICALLY ACCEPTABLE SALT THEREOF<br/>[FR] DÉRIVÉ D'URÉE OU SEL PHARMACOLOGIQUEMENT ACCEPTABLE DE CE DERNIER
  申请人：KYORIN SEIYAKU KK

  公开号：WO2016189877A1

  公开（公告）日：2016-12-01

  The present invention provides a urea compound or a pharmacologically acceptable salt thereof that has a formyl peptide receptor like 1 (hereinafter may be abbreviated as FPRL1) agonist effect, a pharmaceutical composition containing the urea compound or the pharmacologically acceptable salt thereof, and a pharmaceutical use thereof. It has been found that a urea derivative represented by the general formula (I) below or a pharmacologically acceptable salt thereof has a superior FPRL1 agonist effect. Compound (I) or a pharmacologically acceptable salt thereof is highly useful for treatment, prevention, or suppression of inflammatory diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, immune disorders and the like.

  本发明提供了一种尿素化合物或其药理学上可接受的盐，具有类似甲酰肽受体1（以下简称为FPRL1）的激动剂作用，含有该尿素化合物或其药理学上可接受的盐的药物组合物，以及其药用。已发现下述一般式（I）所代表的尿素衍生物或其药理学上可接受的盐具有优越的FPRL1激动剂作用。化合物（I）或其药理学上可接受的盐对于治疗、预防或抑制炎症性疾病、慢性气道疾病、癌症、败血症、过敏症状、HIV逆转录病毒感染、循环障碍、神经炎症、神经障碍、疼痛、朊病、淀粉样变性、免疫障碍等方面非常有用。
• Urea derivative or pharmacologically acceptable salt thereof
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：US10858314B2

  公开（公告）日：2020-12-08

  The present invention provides a urea compound or a pharmacologically acceptable salt thereof that has a formyl peptide receptor like 1 (hereinafter may be abbreviated as FPRL1) agonist effect, a pharmaceutical composition containing the urea compound or the pharmacologically acceptable salt thereof and a pharmaceutical use thereof. It has been found that a urea derivative represented by the general formula (I) below or a pharmacologically acceptable salt thereof has a superior FPRL1 agonist effect. Compound (I) or a pharmacologically acceptable salt thereof is highly useful for treatment, prevention, or suppression of inflammatory diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, immune disorders and the like.

  本发明提供了一种具有类似甲酰肽受体1（以下可简称为FPRL1）激动剂效应的脲化合物或其药理学上可接受的盐、一种含有该脲化合物或其药理学上可接受的盐的药物组合物及其药物用途。研究发现，由以下通式（I）代表的脲衍生物或其药理学上可接受的盐具有优异的 FPRL1 激动剂效果。化合物(I)或其药理学上可接受的盐在治疗、预防或抑制炎症性疾病、慢性气道疾病、癌症、败血症、过敏症状、HIV逆转录病毒感染、循环系统疾病、神经炎症、神经紊乱、疼痛、朊病毒病、淀粉样变性、免疫紊乱等方面非常有用。
• Asymmetric synthesis of (2R, 3S) and (2S, 3R) precursors of β-methyl-histidine, -phenylalanine and -tyrosine
  作者：Guigen Li、Dinesh Pattel、Victor J. Hruby

  DOI：10.1016/s0957-4166(00)80091-9

  日期：1993.11

  A systematic series of (2S, 3R) and (2R, 3S) precursors to beta-methyl-histidine, -phenylalanine and -tyrosine, which are of significant importance in the design of peptide and protein ligands, have been synthesized in high optically purity and yield.
• UREA DERIVATIVE OR PHARMACOLOGICALLY ACCEPTABLE SALT THEREOF
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP3303284A1

  公开（公告）日：2018-04-11
• Efficient method for the total asymmetric synthesis of the isomers of .beta.-methyltyrosine
  作者：Ernesto Nicolas、K. C. Russell、J. Knollenberg、Victor J. Hruby

  DOI：10.1021/jo00078a042

  日期：1993.12

  Alpha-Amino acids modified at the beta-carbon atom can provide topographical constraints when incorporated into a peptide. Such modifications can modulate the physical, chemical, and biological properties of the compound. In order to properly evaluate the effect of such modifications, large-scale asymmetric syntheses of the isomers are needed. A method for the stereoselective large-scale synthesis of an four stereoisomers of beta-methyltyrosine is described in this paper. The stereochemistry of both the alpha- and beta-stereocenters was set using 4-phenyl-2-oxazolidinone as a chiral auxiliary. The key reactions were an asymmetric Michael-like addition of an organocuprate to a chiral alpha,beta-unsaturated acyloxazolidinone (beta center) and subsequent stereoselective electrophilic bromination of the resulting product (alpha center). Conversion of the bromide to the azide, catalyzed hydrolysis to the azido acid with simultaneous recovery of the chiral auxiliary, reduction of the azide, and final deprotection of the phenol group afforded the desired amino acids. In general, the reactions were performed in yields over 80 %, and the isomers were obtained in enantiomeric purities of 98:2 to 99:1.