(2S)-tert-butyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S)-tert-butyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylate；(2S)-2-[(tert-Butyldimethylsiloxy)methyl]-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylate
• 化学式: C₁₇H₃₂F₃NO₄Si
• 分子量: 399.526
• InChiKey: AWDGIIMKCNJZRS-HKALDPMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-tert-butyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylate 在 palladium on activated charcoal potassium tert-butylate 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， -40.0~20.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 生成 (2S,4R)-tert-butyl 2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Stereoselective Synthesis of Boc-Protectedcisandtrans-4-Trifluoromethylprolines by Asymmetric Hydrogenation Reactions

  摘要：

  DOI：

  10.1002/1521-3773(20020503)41:9<1600::aid-anie1600>3.0.co;2-v
• 作为产物：
  描述：

  N-Boc-反式-4-羟基-L-脯氨酸甲酯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 乙醇 、 TEMPO 、 四丁基氟化铵 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2S)-tert-butyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxy-4-(trifluoromethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
  [FR] COMPOSÉS PHARMACEUTIQUES ARYLE, HÉTÉROARYLES ET HÉTÉROCYCLIQUES POUR LE TRAITEMENT DE TROUBLES MÉDICAUX

  摘要：

  提供了抑制补体因子D的抑制剂、药物组合物及其用途，以及它们的制备方法。所提供的化合物包括公式I、公式II、公式III、公式IV和公式V，或其药学上可接受的盐、前药、同位素类似物、N-氧化物或其分离异构体，可选地在药学上可接受的组合物中。本文描述的抑制剂针对因子D并抑制或调节补体级联反应。

  公开号：

  WO2018160889A1

文献信息

• [EN] ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS<br/>[FR] COMPOSÉS PHARMACEUTIQUES ARYLE, HÉTÉROARYLES ET HÉTÉROCYCLIQUES POUR LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2018160889A1

  公开（公告）日：2018-09-07

  Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.

  提供了抑制补体因子D的抑制剂、药物组合物及其用途，以及它们的制备方法。所提供的化合物包括公式I、公式II、公式III、公式IV和公式V，或其药学上可接受的盐、前药、同位素类似物、N-氧化物或其分离异构体，可选地在药学上可接受的组合物中。本文描述的抑制剂针对因子D并抑制或调节补体级联反应。
• [EN] PROTEASE INHIBITORS FOR TREATING OR PREVENTING CORONAVIRUS INFECTION<br/>[FR] INHIBITEURS DE PROTÉASE POUR TRAITER OU PRÉVENIR UNE INFECTION À CORONAVIRUS
  申请人：[en]MERCK SHARP & DOHME LLC

  公开号：WO2023133174A1

  公开（公告）日：2023-07-13

  The present invention provides a compound of Formula I wherein A, M, R1, R2, R3a, R3b, and subscripts m and n are as described herein and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for the treatment, inhibition, or amelioration of one or more disease states that could benefit from inhibition of a coronavirus, including SARS-CoV, MERS-CoV and SARS-CoV-2. The compounds of this invention could further be used in combination with other therapeutically effective agents, including but not limited to, other drugs useful for the treatment of coronavirus infection. The invention furthermore relates to processes for preparing compounds of Formula I, and pharmaceutical compositions which comprise compounds of Formula I and pharmaceutically acceptable salts thereof.
• Stereoselective Synthesis of Boc-Protected<i>cis</i>and<i>trans</i>-4-Trifluoromethylprolines by Asymmetric Hydrogenation Reactions
  作者：Juan R. Del Valle、Murray Goodman

  DOI：10.1002/1521-3773(20020503)41:9<1600::aid-anie1600>3.0.co;2-v

  日期：2002.5.3
• Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode
  作者：Elizabeth A. Jurica、Ximao Wu、Kristin N. Williams、Andres S. Hernandez、David S. Nirschl、Richard A. Rampulla、Arvind Mathur、Min Zhou、Gary Cao、Chunshan Xie、Biji Jacob、Hong Cai、Tao Wang、Brian J. Murphy、Heng Liu、Carrie Xu、Lori K. Kunselman、Michael B. Hicks、Qin Sun、Dora M. Schnur、Doree F. Sitkoff、Elizabeth A. Dierks、Atsu Apedo、Douglas B. Moore、Kimberly A. Foster、Mary Ellen Cvijic、Reshma Panemangalore、Neil A. Flynn、Brad D. Maxwell、Yang Hong、Yuan Tian、Jason J. Wilkes、Bradley A. Zinker、Jean M. Whaley、Joel C. Barrish、Jeffrey A. Robl、William R. Ewing、Bruce A. Ellsworth

  DOI：10.1021/acs.jmedchem.6b01559

  日期：2017.2.23

  A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding K-i and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both G(q)-coupled intracellular Ca2+ flux and G(s)-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.