依拉司群中间体 | 914103-95-0

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 依拉司群中间体
• 英文名称: tert-butyl 4-(bromomethyl)phenethylcarbamate
• 英文别名: tert-butyl N-{2-[4-(bromomethyl)phenyl]ethyl}carbamate；tert-butyl N-[2-[4-(bromomethyl)phenyl]ethyl]carbamate
• CAS: 914103-95-0
• 化学式: C₁₄H₂₀BrNO₂
• 分子量: 314.222
• InChiKey: IBRSMNFKTXUPKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  依拉司群中间体 在 盐酸羟胺 、 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 (R)-tert-butyl 4-((4-fluoro-N-(1-(hydroxyamino)-1-oxopropan-2-yl)-3-methylphenylsulfonamido)methyl)phenethylcarbamate
  参考文献：
  名称：

  Probing the S2′ Subsite of the Anthrax Toxin Lethal Factor Using Novel N-Alkylated Hydroxamates

  摘要：

  The lethal factor (LF) enzyme secreted by Bacillus anthracis is a zinc hydrolase that is chiefly responsible for anthrax-related cell death. Although many studies of the design of small molecule LF inhibitors have been conducted, no LF inhibitor is yet available as a therapeutic agent. Inhibitors with considerable chemical diversity have been developed and investigated; however, the LF S2' subsite has not yet been systematically explored as a potential target for lead optimization. Here we present synthesis, experimental evaluation, modeling, and structural biology for a novel series of sulfonamide hydroxamate LF inhibitor analogues specifically designed to extend into, and probe chemical preferences of, this S2' subsite. We discovered that this region accommodates a wide variety of chemical functionalities and that a broad selection of ligand structural modifications directed to this area can be incorporated without significant deleterious alterations in biological activity. We also identified key residues in this subsite that can potentially be targeted to improve inhibitor binding.

  DOI：

  10.1021/acs.jmedchem.5b01446
• 作为产物：
  描述：

  对甲基苯乙胺 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 依拉司群中间体
  参考文献：
  名称：

  Mechanistic approach of the difference in non-enzymatic hydrolysis rate between the L and D enantiomers of no-carrier added 2-[18F]fluoromethyl-phenylalanine

  摘要：

  无载体添加的(n.c.a.) 2-[18F]氟甲基-l-苯丙氨酸在水溶液中对水解非常敏感。通过添加钙离子 (0.04 M)，该问题部分得到解决，使其货架期延长至至少6小时。本文详细研究了去氟反应，以阐明其机制。因此，合成了2-[18F]FMP和4-[18F]FMP的L和D对映体，以及2-[18F]氟甲基-苯乙胺和4-[18F]氟甲基-苯乙胺，这两者都是氨基酸类的去羧基‘模拟’分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，获得了高的总体产率和>99%的放射化学纯度。通过高效液相色谱(HPLC)研究了所有化合物的去氟速率。n.c.a 2-[18F]FMP的L对映体去氟速率是D对映体和2-[18F]氟甲基-苯乙胺的七倍。4-[18F]FMP和4-[18F]氟甲基-苯乙胺的两个对映体均表现出稳定性。根据这些数据，得出了反应机制，涉及两种不同的分子内相互作用。首先，胺与苯基氟之间的相互作用削弱了碳-氟键。其次，羧基与其中一个苯基氢原子形成的第二个氢桥使氟原子对水解的敏感性进一步增强。后者的相互作用引入了额外的手性中心。这种手性中心的形成概率在n.c.a. 2-[18F]FMP的L和D对映体之间存在显著差异，这解释了水解速率的差异。版权所有 © 2010 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.1811

文献信息

• Mechanistic approach of the difference in hydrolysis rate between the 2- and 4-isomers of no-carrier-added [18F]fluoromethyl-L-phenylalanine
  作者：Ken Kersemans、John Mertens、Frank De Proft、Paul Geerlings

  DOI：10.1002/jlcr.1852

  日期：2011.4

  No-carrier-added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine (2-[18F]FMP) was found to be very sensitive to hydrolysis in aqueous solutions. In this paper, the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, besides 2-[18F]FMP and 4-[18F]FMP, 2-[18F]fluoromethyl-phenethylamine (2-[18F]FMPAM) and 4-[18F]FMPAM were synthesized, both ‘mimetic’ molecules of the decarboxylated amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The defluorination rate of 2-[18F]FMLP at 50°C was approximately 300 times faster than that of n.c.a. 4-[18F]FMLP. The defluorination rate of 2-[18F]FMPAM is somewhat lower than of 2-[18F]FMP but still very high in comparison with 4-[18F]FMPAM, which is virtually stable. It allowed to elucidate the reaction mechanism ruled by two distinct intramolecular interactions. First, the hydrogen bond interaction between the amine and the benzylic fluorine weakening the carbon–fluorine bond. Secondly, the formation of a second hydrogen bond between the carboxyl oxygen atom and one of the benzylic hydrogen atoms rendering the benzyl fluoride group even more susceptible to hydrolysis. Copyright © 2010 John Wiley & Sons, Ltd.

  无载体添加（n.c.a.）的2-[18F]氟甲基-L-苯丙氨酸（2-[18F]FMP）在水溶液中对水解非常敏感。本文对去氟反应进行了详细研究，以阐明其机制。因此，除了合成2-[18F]FMP和4-[18F]FMP之外，还合成了2-[18F]氟甲基-苯乙胺（2-[18F]FMPAM）和4-[18F]FMPAM，这两者均为去羧化氨基酸类似物的“模拟”分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，得到了高的整体产率和>99%的放射化学纯度。通过高效液相色谱（HPLC）研究了所有化合物的去氟速率。2-[18F]FMLP在50°C的去氟速率大约是n.c.a. 4-[18F]FMLP的300倍。2-[18F]FMPAM的去氟速率略低于2-[18F]FMP，但与几乎稳定的4-[18F]FMPAM相比，仍然非常高。这有助于阐明由两种不同的分子内相互作用主导的反应机制。首先，是胺和苄基氟之间的氢键相互作用，削弱了碳-氟键。其次，羧氧原子与一个苄基氢原子之间形成第二个氢键，使得苄基氟烷基团更易于水解。版权 © 2010 John Wiley & Sons, Ltd.
• Thienopyrimidone compound
  申请人：Murata Toshiki

  公开号：US20100069362A1

  公开（公告）日：2010-03-18

  The present invention relates to a compound represented by the formula: wherein Ar is an optionally substituted ring; A is a spacer having a main chain of 1 to 4 atoms; B is a bond, a C 1-10 alkylene group or an oxygen atom; R 3 and R 5 are each independently a hydrogen atom or a substituent; R 4 is an optionally substituted cyclic group or an optionally substituted C 1-10 alkyl group; and R 1 and R 2 are each independently a hydrogen atom or a substituent, or R 1 and R 2 or R 1 and B are bonded to form an optionally substituted nitrogen-containing heterocycle, or R 1 and Ar are bonded to form an optionally substituted nitrogen-containing fused heterocycle, or a salt thereof. The thienopyrimidone compound of the present invention has a superior melanin-concentrating hormone receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of obesity and the like.

  本发明涉及一种化合物，其表示为以下公式： 其中，Ar是可选取代环；A是具有1到4个原子的主链间隔物；B是键合、C1-10烷基或氧原子；R3和R5各自独立地是氢原子或取代基；R4是可选取代的环状基团或可选取代的C1-10烷基基团；而R1和R2各自独立地是氢原子或取代基，或者R1和R2或R1和B被键合形成可选取代的含氮杂环，或者R1和Ar被键合形成可选取代的含氮融合杂环，或其盐。本发明的噻唑嘧啶酮化合物具有优异的黑色素浓集激素受体拮抗作用，可用作预防或治疗肥胖等药物。
• G9A INHIBITOR
  申请人：RIKEN

  公开号：EP4066896A1

  公开（公告）日：2022-10-05

  A compound represented by the general formula (I) given below or a pharmacologically acceptable salt thereof has been found to have a strong G9a inhibitory effect. The compound (I) or the pharmacologically acceptable salt thereof inhibits G9a and thereby has high usefulness for the treatment, prevention or suppression of various pathological conditions (proliferative disease such as cancer, β-globin abnormality, fibrosis, pain, neurodegenerative disease, Prader-Willi syndrome, malaria, viral infection, myopathy, autism, etc.).

  一种由下列通式（I）表示的化合物或其药理学上可接受的盐已被发现具有强烈的G9a抑制作用。该化合物（I）或其药理学上可接受的盐抑制G9a，因此在治疗、预防或抑制各种病理状况（如增殖性疾病，如癌症，β-珠蛋白异常，纤维化，疼痛，神经退行性疾病，普拉德-威利综合症，疟疾，病毒感染，肌肉病，自闭症等）方面具有高度的有用性。
• Non-systemic TGR5 agonists
  申请人：Venenum Biodesign, LLC

  公开号：US10654834B2

  公开（公告）日：2020-05-19

  The present invention relates to tricyclic compounds of formula (I) and formula (II), or a pharmaceutically acceptable salt thereof. The present tricyclic compounds are useful non-systemic TGR5 agonists that can be used to treat diabetic diseases in human. The present invention provides a pharmaceutical composition containing tricyclic compounds of formula (I) and formula (II) and a method of making as well as a method of using same in treating patients inflicted with metabolic disorders by administering same. The compounds of the present invention may be used in combination with additional anti-diabetic drugs.

  本发明涉及式（I）和式（II）的三环化合物或其药学上可接受的盐。本发明的三环化合物是有用的非系统性 TGR5 激动剂，可用于治疗人类糖尿病疾病。本发明提供了一种含有式（I）和式（II）三环化合物的药物组合物及其制造方法，以及一种通过给药治疗代谢紊乱患者的方法。本发明的化合物可与其他抗糖尿病药物联合使用。
• Thienopyrimidone compounds
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1876179B1

  公开（公告）日：2015-03-25