(4-fluorobenzyl) 2,2,2-trichloroacetimidate | 214139-63-6

• 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: (4-fluorobenzyl) 2,2,2-trichloroacetimidate
• 英文别名: (4-fluorophenyl)methyl 2,2,2-trichloroethanimidate；4-fluorobenzyl trichloroacetimidate；4-fluorbenzyl trichloroacetimidate
• CAS: 214139-63-6
• 化学式: C₉H₇Cl₃FNO
• 分子量: 270.518
• InChiKey: UVASVERMYZIPPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-fluorobenzyl) 2,2,2-trichloroacetimidate 在 2-羟基吡啶 、 三氟甲磺酸 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 N1,N6-di[(1S)-2-methyl-1-(methylcarbamoyl)propyl]-(2R,3R,4R,5R)-2,5-di[(4-fluorobenzyl)oxy]-3,4-dihydroxyhexanediamide
  参考文献：
  名称：

  Design and Synthesis of Potent C₂-Symmetric Diol-Based HIV-1 Protease Inhibitors:  Effects of Fluoro Substitution

  摘要：

  Implementation of derivatized carbohydrates as C-2-symmetric HIV-1 protease inhibitors has previously been reported. With the objective of improving the anti-HIV activity of such compounds, we synthesized a series of fluoro substituted P1/P1 ' analogues. These compounds were evaluated for antiviral activity toward both wild type and mutant virus. The potency of the analogues in blocking HIV-1 protease was moderate, with K-i values ranging from 1 to 7 nM. Nonetheless, compared to the parent nonfluorous inhibitors, a majority of the compounds exhibited improved antiviral activity, for example the 3-fluorobenzyl derivative 9b, which had a K-i value of 7.13 nM and displayed one of the most powerful antiviral activities in the cellular assay of the series. Our results strongly suggest that fluoro substitution can substantially improve antiviral activity. The X-ray crystal structures of two of the fluoro substituted inhibitors (9a and 9f) cocrystallized with HIV-1 protease are discussed.

  DOI：

  10.1021/jm001134q
• 作为产物：
  描述：

  对氟苯甲醇 生成 (4-fluorobenzyl) 2,2,2-trichloroacetimidate
  参考文献：
  名称：

  Antiviral protease inhibitors

  摘要：

  公式I的化合物：其中：A′和A″分别是公式II的相同或不同基团：其中：R′为H、CH3、C(CH3)2、—ORa、—N(Ra)2、—N(Ra)ORa或—DPR′″为H或CH3；Ra为H、C1-C3烷基；D为键、烷基、—C(═O)—、—S(O)—或—S(O)2—；P为可选取代的、单环或双环碳氢或杂环；R″为H、天然氨基酸中发现的任何侧链、羧基乙酰胺或(CH2)nDP群；M为键或—C(═O)N(R′″)—；Q为不存在、键、—CH(OH)—或—CH2—；或者R″与Q、M和R′一起定义一个可选取代的5或6成员碳氢或杂环，该环可选地与另一个5或6成员碳氢或杂环融合；但R′为—ORa、—N(Ra)2、—N(Ra)ORa或—DP，如果M为键且Q不存在；X为H、OH、OCH3；Y为H、OH、OCH3，但X和Y不能同时为H；Z′和Z″独立地为—(CH2)mP，其中P如上定义；n和m独立地为0、1或2；以及其药学上可接受的盐和前药作为HIV的天冬氨酸蛋白酶抑制剂具有实用性。它们可以从新型2,5-二-O-苄基-L-甘露糖-1,4:6,3-二内酯中间体中方便地进行两步合成。

  公开号：

  US06291687B1

文献信息

• Synthesis, in Vitro Pharmacology, Structure−Activity Relationships, and Pharmacokinetics of 3-Alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Derivatives as Potent and Selective Group II Metabotropic Glutamate Receptor Antagonists
  作者：Atsuro Nakazato、Kazunari Sakagami、Akito Yasuhara、Hiroshi Ohta、Ryoko Yoshikawa、Manabu Itoh、Masato Nakamura、Shigeyuki Chaki

  DOI：10.1021/jm0400294

  日期：2004.8.1

  Novel group II metabotropic glutamate receptor (mGluR) antagonists, 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, were discovered by the incorporation of a hydroxy or alkoxyl group onto the C-3 portion of selective and potent group II mGluR agonist 5, (1R,2S,5R,6R)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid. Among these compounds, (1R,2R

  通过掺入羟基或烷氧基，发现了新型的II类代谢型谷氨酸受体（mGluR）拮抗剂3-烷氧基-2-氨基-6-氟双环[3.1.0]己烷-2,6-二羧酸衍生物11和12。在选择性和有效的第II组mGluR激动剂5（1R，2S，5R，6R）-2-氨基-6-氟双环[3.1.0]己烷-2,6-二羧酸的C-3部分上连接基团 在这些化合物中，（1R，2R，3R，5R，6R）-2-氨基-3-（3,4-二氯苄氧基）-6-氟双环[3.1.0]己烷-2,6-二羧酸（-）- 11be（MGS0039）是一种具有最佳药代动力学特征的高选择性强效II组mGluR拮抗剂。化合物（-）-11对mGlu 2（Ki = 2.38 +/- 0.40 nM）和mGlu 3（4.46 +/- 0.31 nM）表现出高亲和力，但对mGluR 7（Ki = 664 +/- 106 nM）的亲和力低，和有效的mGlu 2拮抗剂活性（IC50 =
• [EN] PRODRUG OF AMINO ACID DERIVATIVE<br/>[FR] PROMÉDICAMENT DE DÉRIVÉ D'ACIDE AMINÉ
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2017183734A1

  公开（公告）日：2017-10-26

  Provided is an amino acid derivative prodrug represented by general formula (I-A) that is a prodrug form of an amino acid derivative which is a group 2 metabotropic glutamate receptor antagonist, or a pharmaceutically acceptable salt thereof. More specifically, provided is an amino acid derivative prodrug represented by general formula (I-A) that is a preventive or therapeutic drug for mood disorders (including depression and bipolar disorder), anxiety disorder, cognitive disorders, developmental disorders, Alzheimer's disease, Parkinson's disease, movement disorders associated with muscular rigidity, sleep disorders, Huntington's chorea, eating disorders, drug dependence, epilepsy, brain infarction, cerebral ischemia, cerebral insufficiency, cerebral edema, spinal cord disorders, head trauma, inflammation and immune- related diseases, and so on.

  提供的是一种氨基酸衍生物前药，代表为一般式(I-A)，它是一种群2代谷氨酸代谢型谷氨酸受体拮抗剂的前药形式，或其药学上可接受的盐。更具体地，提供的是一种氨基酸衍生物前药，代表为一般式(I-A)，用于预防或治疗情绪障碍（包括抑郁症和躁郁症）、焦虑症、认知障碍、发育障碍、阿尔茨海默病、帕金森病、伴有肌肉僵硬的运动障碍、睡眠障碍、亨廷顿舞蹈症、进食障碍、药物依赖、癫痫、脑梗死、脑缺血、脑供血不足、脑水肿、脊髓疾病、头部创伤、炎症和免疫相关疾病等。
• Gold(I)-catalyzed arylmethylation of terminal alkynes
  作者：Changkun Li、Weibin Li、Jianbo Wang

  DOI：10.1016/j.tetlet.2009.03.067

  日期：2009.5

  AuCl/AgOTf catalyzes the reaction of terminal alkynes with aryl trichloroacetimidate to afford arylmethylation products in moderate to good yields.

  AuCl / AgOTf催化末端炔烃与芳基三氯乙酰亚胺酸酯的反应，以中等至良好的收率提供芳基甲基化产物。
• 6-Fluorobicyclo[3.1.0]hexane derivatives
  申请人：Nakazato Atsuro

  公开号：US20050119345A1

  公开（公告）日：2005-06-02

  An antidepressant comprising, as an active ingredient, a compound having an antagonistic effect on group II metabotropic glutamate receptors, as well as a 2-amino-3-alkoxy-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative of Formula [I]: [wherein R 1 and R 2 , which may be the same or different, each represent a hydroxyl group, a C 1-10 alkoxy group, etc.; R 3 represents a C 1-10 acyl group, a C 1-6 alkoxy-C 1-6 acyl group, etc.; and R 4 and R 5 , which may be the same or different, each represent a hydrogen atom, a C 1-10 alkyl group, etc.] or a pharmaceutically acceptable salt or hydrate thereof.

  一种抗抑郁药，包含作为活性成分的一种具有对II类代谢型谷氨酸受体拮抗作用的化合物，以及公式[I]的2-氨基-3-烷氧基-6-氟-双环[3.1.0]己烷-2,6-二羧酸衍生物：[其中R1和R2，可以相同或不同，分别代表羟基，C1-10烷氧基等；R3代表C1-10酰基，C1-6烷氧基-C1-6酰基等；R4和R5，可以相同或不同，分别代表氢原子，C1-10烷基等]或其药学上可接受的盐或水合物。
• Prodrug of amino acid derivative
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：US10464884B2

  公开（公告）日：2019-11-05

  Provided is an amino acid derivative prodrug represented by general formula (I-A) that is a prodrug form of an amino acid derivative which is a group 2 metabotropic glutamate receptor antagonist, or a pharmaceutically acceptable salt thereof. More specifically, provided is an amino acid derivative prodrug represented by general formula (I-A) that is a preventive or therapeutic drug for mood disorders (including depression and bipolar disorder), anxiety disorder, cognitive disorders, developmental disorders, Alzheimer's disease, Parkinson's disease, movement disorders associated with muscular rigidity, sleep disorders, Huntington's chorea, eating disorders, drug dependence, epilepsy, brain infarction, cerebral ischemia, cerebral insufficiency, cerebral edema, spinal cord disorders, head trauma, inflammation and immune-related diseases, and so on.

  本发明提供了一种由通式（I-A）表示的氨基酸衍生物原药，它是第 2 组代谢谷氨酸受体拮抗剂的氨基酸衍生物的原药形式，或其药学上可接受的盐。 更具体地说，所提供的通式（I-A）所代表的氨基酸衍生物原药是一种预防或治疗药物，可用于治疗情绪障碍（包括抑郁症和双相情感障碍）、焦虑症、认知障碍、发育障碍、阿尔茨海默病、帕金森病、与肌肉僵硬相关的运动障碍、与肌肉僵硬有关的运动障碍、睡眠障碍、亨廷顿舞蹈症、饮食失调、药物依赖、癫痫、脑梗塞、脑缺血、脑供血不足、脑水肿、脊髓疾病、头部创伤、炎症和免疫相关疾病等。