N-<amino>carbonyl>valine | 202817-20-7

• 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
• 英文名称: N-<amino>carbonyl>valine
• 英文别名: (2S)-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanoic Acid；(2S)-3-methyl-2-[[methyl-[(2-methyl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoic acid
• CAS: 202817-20-7
• 化学式: C₁₂H₁₉N₃O₃S
• mdl: MFCD16531353
• 分子量: 285.367
• InChiKey: NWKQCPXPKVNTBJ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.583
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-<amino>carbonyl>valine 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 (2S,3S,5S)-5-amino>carbonyl>valinyl>amino>-2-carbonyl>amino>-1,6-diphenyl-3-hydroxyhexane
  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：

  N-(4-硝基苯基氧基-羰基)-l-缬氨酸甲酯 在 4-二甲氨基吡啶 、 lithium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 N-<amino>carbonyl>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+

文献信息

• HIV protease inhibiting compounds
  申请人：Flentge Charles A.

  公开号：US20110003827A1

  公开（公告）日：2011-01-06

  A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

  公开了一种具有以下公式的化合物，作为HIV蛋白酶抑制剂。还公开了抑制HIV感染的方法和组合物。
• HIV PROTEASE INHIBITING COMPOUNDS
  申请人：Flentge Charles A.

  公开号：US20130023463A1

  公开（公告）日：2013-01-24

  A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

  该化合物的公式被披露为HIV蛋白酶抑制剂。还披露了抑制HIV感染的方法和组合物。
• Hiv protease inhibiting sulfonamides
  申请人：Abbott Laboratories

  公开号：EP2216334A1

  公开（公告）日：2010-08-11

  A compound of the formula is disclosed as an I-IIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

  式中的化合物 公开了一种 I-IIV 蛋白酶抑制剂。还公开了抑制艾滋病毒感染的方法和组合物。
• WO2008/10921
  申请人：——

  公开号：——

  公开（公告）日：——
• Structure–activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350)
  作者：Lianhong Xu、Hongtao Liu、Allen Hong、Randy Vivian、Bernard P. Murray、Christian Callebaut、You-Chul Choi、Melody S. Lee、Jennifer Chau、Luong K. Tsai、Kirsten M. Stray、Robert G. Strickley、Jianhong Wang、Leah Tong、Swami Swaminathan、Gerry R. Rhodes、Manoj C. Desai

  DOI：10.1016/j.bmcl.2013.12.057

  日期：2014.2

  The HIV protease inhibitor (PI) ritonavir (RTV) has been widely used as a pharmacoenhancer for other PIs, which are substrates of cytochrome P450 3A (CYP3A). However the potent anti-HIV activity of ritonavir may limit its use as a pharmacoenhancer with other classes of anti-HIV agents. Ritonavir is also associated with limitations such as poor physicochemical properties. To address these issues a series of compounds with replacements at the P2 and/or P3 region was designed and evaluated as novel CYP3A inhibitors. Through these efforts, a potent and selective inhibitor of CYP3A, GS-9350 (cobicistat) with improved physiochemical properties was discovered. (C) 2013 Elsevier Ltd. All rights reserved.