Carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester | 144186-12-9

• 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: Carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester
• 英文别名: [6-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-pyridinyl]methyl 4-nitrophenyl carbonate；[6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-3-yl]methyl (4-nitrophenyl) carbonate
• CAS: 144186-12-9
• 化学式: C₁₈H₁₉N₃O₇
• 分子量: 389.365
• InChiKey: ZXRQQLLSZMJDKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl ester 在 N-甲基吗啉 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 生成 N-<<<6-<(tert-butyloxycarbonyl)amino>-3-pyridinyl>methoxy>carbonyl>-L-valine
  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：

  6-氨基烟酸甲酯 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 Carbonic acid 6-tert-butoxycarbonylamino-pyridin-3-ylmethyl ester 4-nitro-phenyl 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

• Structural Basis for Genetic-Code Expansion with Bulky Lysine Derivatives by an Engineered Pyrrolysyl-tRNA Synthetase
  作者：Tatsuo Yanagisawa、Mitsuo Kuratani、Eiko Seki、Nobumasa Hino、Kensaku Sakamoto、Shigeyuki Yokoyama

  DOI：10.1016/j.chembiol.2019.03.008

  日期：2019.7

  non-natural lysine derivatives by UAG. In this study, we examined how PylRS(Y306A/Y384F) recognizes many amino acids. Among 17 non-natural lysine derivatives, Nɛ-(benzyloxycarbonyl)lysine (ZLys) and 10 ortho/meta/para-substituted ZLys derivatives were efficiently ligated to tRNAPyl and were incorporated into proteins by PylRS(Y306A/Y384F). We determined crystal structures of 14 non-natural lysine derivatives

  Pyrrolysyl-tRNA合成酶（PylRS）和tRNAPyl已被广泛用于遗传密码扩展。带有Y306A和Y384F突变的马氏甲烷八叠球菌PylRS突变体（PylRS（Y306A / Y384F））通过UAG编码各种庞大的非天然赖氨酸衍生物。在这项研究中，我们检查了PylRS（Y306A / Y384F）如何识别许多氨基酸。在17种非天然赖氨酸衍生物中，N +-（苄氧羰基）赖氨酸（ZLys）和10种邻/间/对位/对位取代的ZLys衍生物被有效地连接到tRNAPyl上，并通过PylRS（Y306A / Y384F）掺入蛋白质中。我们确定了绑定到PylRS（Y306A / Y384F）催化片段的14种非天然赖氨酸衍生物的晶体结构。将间位和对位取代的ZLys衍生物紧密地容纳在生产模式中。相比之下，ZLys和未取代或邻位取代的ZLys衍生物除生产模式外还表现出其他结合模式。PylRS（Y306A
• Retroviral protease inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0486948A2

  公开（公告）日：1992-05-27

  A retroviral protease inhibiting compound of the formula A -X- B is disclosed. Also disclosed are a composition and method for inhibiting a retroviral protease and for treating an HIV infection. Also disclosed are processes and intermediates useful for the preparation of the retroviral protease inhibitors.

  本发明公开了一种式 A -X- B 的逆转录病毒蛋白酶抑制化合物。还公开了一种抑制逆转录病毒蛋白酶和治疗 HIV 感染的组合物和方法。还公开了用于制备逆转录病毒蛋白酶抑制剂的工艺和中间体。
• Intermediates for preparing retroviral protease inhibiting compounds
  申请人：Abbott Laboratories

  公开号：EP0997459A1

  公开（公告）日：2000-05-03

  An intermediate of the formula: and an intermediate of the formula: or an acid addition salt thereof.

  公式的中间体： 和 式的中间体 或其酸加成盐。
• US5648497A
  申请人：——

  公开号：US5648497A

  公开（公告）日：1997-07-15
• US5837873A
  申请人：——

  公开号：US5837873A

  公开（公告）日：1998-11-17