(S)-4-((tert-butoxycarbonyl)amino)-2-(methylamino)butanoic acid methyl ester | 201867-49-4

• 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
• 英文名称: (S)-4-((tert-butoxycarbonyl)amino)-2-(methylamino)butanoic acid methyl ester
• 英文别名: (S)-methyl 4-((tert-butoxycarbonyl)amino)-2-(methylamino)butanoate；(S)-Methyl 4-((tert-butoxycarbonyl)amino)-2-(methylamino)butanoate；methyl (2S)-2-(methylamino)-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 201867-49-4
• 化学式: C₁₁H₂₂N₂O₄
• 分子量: 246.307
• InChiKey: XSGFRUNTFUNKSM-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3,5-dimethyl-biphenyl-4-carboxylic acid chloride 、 (S)-4-((tert-butoxycarbonyl)amino)-2-(methylamino)butanoic acid methyl ester 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到(S)-2-{[3'-(4-chloro-2,5-dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]methylamino}-4-tert-butoxycarbonylaminobutyric acid methyl ester
  参考文献：
  名称：

  An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation

  摘要：

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.

  DOI：

  10.1021/jm3009508
• 作为产物：
  描述：

  (2S)-2-氨基-4-[(叔丁氧羰基)氨基]丁酸甲酯 在 potassium carbonate 、 苯硫酚 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 (S)-4-((tert-butoxycarbonyl)amino)-2-(methylamino)butanoic acid methyl ester
  参考文献：
  名称：

  [EN] MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
  [FR] ANTIBIOTIQUES MACROCYCLIQUES À LARGE SPECTRE

  摘要：

  本文提供了抗菌化合物，其中在某些实施例中，这些化合物具有广谱生物活性。在各种实施例中，这些化合物通过抑制细菌类型1信号肽酶（SpsB）发挥作用，这是细菌中的一种必需蛋白质。还提供了使用所述化合物的药物组合物和治疗方法。

  公开号：

  WO2017084630A1

文献信息

• [EN] METHODS AND INTERMEDIATES FOR PREPARING PHARMACEUTICAL AGENTS<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES POUR LA PRÉPARATION D'AGENTS PHARMACEUTIQUES
  申请人：GILEAD SCIENCES INC

  公开号：WO2013116715A1

  公开（公告）日：2013-08-08

  Methods and intermediates useful for preparing a compound of formula I and salts thereof.

  用于制备式I化合物及其盐的方法和中间体。
• MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
  申请人：RQX PHARMACEUTICALS, INC.

  公开号：US20180327367A1

  公开（公告）日：2018-11-15

  Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
• An Oral Sphingosine 1-Phosphate Receptor 1 (S1P₁) Antagonist Prodrug with Efficacy in Vivo: Discovery, Synthesis, and Evaluation
  作者：Daniela Angst、Philipp Janser、Jean Quancard、Peter Buehlmayer、Frederic Berst、Lukas Oberer、Christian Beerli、Markus Streiff、Charles Pally、Rene Hersperger、Christian Bruns、Frederic Bassilana、Birgit Bollbuck

  DOI：10.1021/jm3009508

  日期：2012.11.26

  A prodrug approach to optimize the oral exposure :of a series of sphingosine 1-phosphate receptor 1 (S1P(1)) antagonists for chronic efficacy studies led to the discovery of dimethylphenylsulfonylamino)-3,5-dimethylbiphenyl-4-carbonyl]-methylamino}-4-dimethylaminobutyric acid methyl ester 14. Methyl ester prodrug 14 is hydrolyzed in vivo to the corresponding carboxylic, acid 15, a potent and selective S1P(1) antagonist.: Oral; administration of the prodrug 14 induces sustained peripheral blood lymphocyte reduction.. in rats. In a rat: cardiac transplantation model coadministration of a nonefficacious dose of prodrung 14 with a nonefficacious dose of sotrastaurin (19), a protein kinase C inhibitor, or everolimus mTOR inhibitor, effectively prolonged the survival time of rat cardiac allografts. This demonstrates that clinically useful immunomodulation mediated by the S1P(1) receptor can be achieved with an S1P(1) antagonist generated in vivo after oral administration of its prodrug.
• [EN] MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES MACROCYCLIQUES À LARGE SPECTRE
  申请人：RQX PHARMACEUTICALS INC

  公开号：WO2017084630A1

  公开（公告）日：2017-05-26

  Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

  本文提供了抗菌化合物，其中在某些实施例中，这些化合物具有广谱生物活性。在各种实施例中，这些化合物通过抑制细菌类型1信号肽酶（SpsB）发挥作用，这是细菌中的一种必需蛋白质。还提供了使用所述化合物的药物组合物和治疗方法。