N-BOC-R-2-氯苯甘氨酸 | 1212602-23-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N-BOC-R-2-氯苯甘氨酸
• 英文名称: (2R)-[(tert-butoxycarbonyl)amino](2-chlorophenyl)ethanoic acid
• 英文别名: (R)-2-((tert-Butoxycarbonyl)amino)-2-(2-chlorophenyl)acetic acid；(2R)-2-(2-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid
• CAS: 1212602-23-7
• 化学式: C₁₃H₁₆ClNO₄
• 分子量: 285.727
• InChiKey: XPFJZGJBRMTXCE-SNVBAGLBSA-N

物化性质

• 沸点：
  431.5±40.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

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：
  0.38
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  ethyl 2-[({[(2-hydroxyethyl)amino]carbonyl}oxy)methyl]-5,7-dimethyl-3-{2-[(methylamino)sulfonyl]phenyl}-4-oxo-3,4-dihydroquinazoline-6-carboxylate 、 N-BOC-R-2-氯苯甘氨酸 在 4-二甲氨基吡啶 、 1,2-二氯乙烷 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  An Effective Prodrug Strategy to Selectively Enhance Ocular Exposure of a Cannabinoid Receptor (CB_1/2) Agonist

  摘要：

  Glaucoma is a leading cause of vision loss and blindness with increased intraocular pressure (IOP) a prominent risk factor. IOP can be efficaciously reduced by administration of topical agents. However, the repertoire of approved IOP-lowering drug classes is limited, and effective new alternatives are needed. Agonism of the cannabinoid receptor's CB1/2 significantly reduces IOP clinically and experimentally. However, development of CB1/2 agonists has been complicated by the need to avoid cardiovascular and psychotropic side effects. 1 is a potent CB1/2 agonist that is highly excluded from the brain. In a phase I study, compound 1 eyedrops were well tolerated and generated an IOP-lowering trend but were limited in dose and exposure due to poor soluhility and ocular absorption. Here we present an innovative strategy to rapidly identify compound 1 prodrugs that are efficiently metabolized to the parent compound for improved solubility and ocular permeability while maintaining low systemic exposures.

  DOI：

  10.1021/jm4004939
• 作为产物：
  描述：

  tert-butyl (2-(2-chlorophenyl)acetoxy)carbamate 在 2,2,6,6-四甲基哌啶 、 C₂₆H₃₀Cl₂F₂FeN₆ 作用下， 以 氯仿 、 邻二氯苯 为溶剂， 以88%的产率得到
  参考文献：
  名称：

  通过 1,3-氮迁移合成 α-氨基酸：更新

  摘要：

  报道了一种通过立体控制重排合成非外消旋非天然 α-氨基酸的改进实用且有效的程序。羧酸转化为氮杂环酯 RCO 2 NHBoc，然后通过铁催化的 1,3-氮迁移，以不对称（α-单取代 α-氨基酸）或形式提供非外消旋 α-氨基酸对映体趋同方式（α,α-二取代的 α-氨基酸）。在优化条件下，以氟化手性铁催化剂和2,2,6,6-四甲基哌啶为碱，在1,2-二氯苯和CHCl 3 的溶剂混合物中，对映选择性高达98% ee获得。如此高的 ee 值对于实际目的很重要，允许直接使用许多获得的 N-Boc 保护的 α-氨基酸用于后续应用。

  DOI：

  10.1055/s-0043-1775371

文献信息

• [EN] PYRROLIDINE-PYRAZOLES AS PYRUVATE KINASE ACTIVATORS<br/>[FR] PYRROLIDINE-PYRAZOLES EN TANT QU'ACTIVATEURS DE LA PYRUVATE KINASE
  申请人：GLOBAL BLOOD THERAPEUTICS INC

  公开号：WO2021202796A1

  公开（公告）日：2021-10-07

  The subject matter described herein is directed to pyruvate kinase activating compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds and methods of administering the compounds for the treatment of diseases associated with PKR and/or PKM2, such as pyruvate kinase deficiency, sickle cell disease, and beta-thalassemia.

  本文描述的主题是针对式I的丙酮酸激酶激活化合物及其药用盐，制备这些化合物的方法，包含这些化合物的药物组合物以及用于治疗与PKR和/或PKM2相关疾病的化合物的给药方法，例如丙酮酸激酶缺乏症、镰状细胞病和β地中海贫血。
• Discovery of a phenylpyrazole amide ROCK inhibitor as a tool molecule for in vivo studies
  作者：Zilun Hu、Cailan Wang、Peter W. Glunz、Julia Li、Nathan L. Cheadle、Alice Y. Chen、Xue-Qing Chen、Joseph E. Myers、Victor R. Guarino、Anne Rose、John S. Sack、Doree Sitkoff、David S. Taylor、Songmei Xu、Chunhong Yan、Hongwei Zhang、Lisa Zhang、James Hennan、Leonard P. Adam、Ruth R. Wexler、Mimi L. Quan

  DOI：10.1016/j.bmcl.2020.127495

  日期：2020.11

  Structure-activity relationship optimization on a series of phenylpyrazole amides led to the identification of a dual ROCK1 and ROCK2 inhibitor (25) which demonstrated good potency, kinome selectivity and favorable pharmacokinetic profiles. Compound 25 was selected as a tool molecule for in vivo studies including evaluating hemodynamic effects in telemeterized mice, from which moderate decreases in

  在一系列苯基吡唑酰胺上进行结构-活性关系优化后，鉴定出了双重ROCK1和ROCK2抑制剂（25），该抑制剂表现出良好的效能，运动学选择性和良好的药代动力学特征。选择化合物25作为体内研究的工具分子，包括评估遥测小鼠的血液动力学效应，从中观察到血压有适度下降。
• Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel
  作者：Patrizia Ferraboschi、Maria De Mieri、Fiorella Galimberti

  DOI：10.1016/j.tetasy.2010.06.040

  日期：2010.9

  The (S)-2-chlorophenylglycine moiety is well recognized in the structure of (S)-clopidogrel, a known antithrombotic drug. We prepared an enantiomerically pure chiral building block via an enzyme-catalyzed resolution of (RS)-N-Boc-2-chlorophenylglycine methylester. The best results were obtained by means of an immobilized subtilisin, the cross-linked enzyme aggregate (Alcalase-CLEA (R)). The high enantiomeric excess of the synthon obtained remained the same over the course of clopidogrel synthesis; the simplicity of the process makes this pathway suitable for large-scale preparation. (C) 2010 Elsevier Ltd. All rights reserved.
• An Effective Prodrug Strategy to Selectively Enhance Ocular Exposure of a Cannabinoid Receptor (CB_1/2) Agonist
  作者：Nello Mainolfi、James Powers、Jakal Amin、Debby Long、Wendy Lee、Margaret E. McLaughlin、Bruce Jaffee、Christopher Brain、Jason Elliott、Jeremy M. Sivak

  DOI：10.1021/jm4004939

  日期：2013.7.11

  Glaucoma is a leading cause of vision loss and blindness with increased intraocular pressure (IOP) a prominent risk factor. IOP can be efficaciously reduced by administration of topical agents. However, the repertoire of approved IOP-lowering drug classes is limited, and effective new alternatives are needed. Agonism of the cannabinoid receptor's CB1/2 significantly reduces IOP clinically and experimentally. However, development of CB1/2 agonists has been complicated by the need to avoid cardiovascular and psychotropic side effects. 1 is a potent CB1/2 agonist that is highly excluded from the brain. In a phase I study, compound 1 eyedrops were well tolerated and generated an IOP-lowering trend but were limited in dose and exposure due to poor soluhility and ocular absorption. Here we present an innovative strategy to rapidly identify compound 1 prodrugs that are efficiently metabolized to the parent compound for improved solubility and ocular permeability while maintaining low systemic exposures.