N-isobutyryl-L-serine methyl ester | 162740-05-8

• 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: N-isobutyryl-L-serine methyl ester
• 英文别名: methyl (2S)-3-hydroxy-2-(2-methylpropanoylamino)propanoate
• CAS: 162740-05-8
• 化学式: C₈H₁₅NO₄
• 分子量: 189.211
• InChiKey: KSRBLJQQSYXEIL-LURJTMIESA-N

物化性质

• 沸点：
  378.9±27.0 °C(Predicted)
• 密度：
  1.124±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-isobutyryl-L-serine methyl ester 在 potassium phosphate 、 Trifluorosulfonic anhydride 、 二苯基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 以79%的产率得到甲基(4S)-2-异丙基-4,5-二氢-1,3-恶唑-4-羧酸酯
  参考文献：
  名称：

  Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy

  摘要：

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.

  DOI：

  10.1021/jm970636+
• 作为产物：
  描述：

  L-丝氨酸甲酯盐酸盐 、 异丁酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以53%的产率得到N-isobutyryl-L-serine methyl ester
  参考文献：
  名称：

  Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy

  摘要：

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.

  DOI：

  10.1021/jm970636+

文献信息

• FACILE AMIDE FORMATION VIA S-NITROSO THIOACID INTERMEDIATES
  申请人：Xian Ming

  公开号：US20120190820A1

  公开（公告）日：2012-07-26

  Provided are methods for forming a reactive S-nitroso thioacid (NTA), comprising nitrosation of a thioacid with a nitrosation reagent. Also provided are methods for: acylating a nucleophile including selective acylation with a high degree of selectivity toward amines over hydroxyls; amide or peptide bond formation; forming a dipeptide or polypeptide; and peptide coupling/ligation, comprising use of thioacid and amine starting materials, wherein the reactions are mediated by very reactive S-nitroso thioacid (NTA) intermediates enabling extremely fast reactions under mild conditions, providing for broad applications.

  提供了形成反应性S-亚硝基硫酸（NTA）的方法，包括使用亚硝基试剂对硫酸进行亚硝基化。还提供了以下方法：酰化亲核试剂，包括对胺的选择性酰化，对羟基的选择性度高；酰胺或肽键形成；形成二肽或多肽；以及肽偶联/连接，包括使用硫酸和胺起始物质，其中反应由非常反应性的S-亚硝基硫酸（NTA）中间体介导，在温和条件下实现极快速的反应，适用于广泛的应用。
• RETROVIRAL PROTEASE INHIBITING COMPOUNDS
  申请人：ABBOTT LABORATORIES

  公开号：EP0683772A1

  公开（公告）日：1995-11-29
• EP0683772A4
  申请人：——

  公开号：EP0683772A4

  公开（公告）日：1995-09-27
• US5461067A
  申请人：——

  公开号：US5461067A

  公开（公告）日：1995-10-24
• US5621109A
  申请人：——

  公开号：US5621109A

  公开（公告）日：1997-04-15