N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-2-(ethyl(methyl)amino)-N-isobutylbenzo[d]oxazole-6-carboxamide | 1160490-17-4

• 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: N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-2-(ethyl(methyl)amino)-N-isobutylbenzo[d]oxazole-6-carboxamide
• 英文别名: N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-[ethyl(methyl)amino]-N-(2-methylpropyl)-1,3-benzoxazole-6-carboxamide
• CAS: 1160490-17-4
• 化学式: C₂₅H₃₄N₄O₃
• 分子量: 438.57
• InChiKey: DFLIMBRYXYCMDD-RBBKRZOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  95.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-2-(ethyl(methyl)amino)-N-isobutylbenzo[d]oxazole-6-carboxamide 、 benzo[d]-[1,3]dioxol-5-ylmethyl 4-nitrophenyl carbonate 在 4-二甲氨基吡啶 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到benzo[d][1,3]dioxol-5-ylmethyl (2S,3R)-4-(2-(ethyl(methyl)amino)-N-isobutylbenzo[d]oxazole-6-carboxamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  参考文献：
  名称：

  AMIDE COMPOUNDS AS BOOSTERS OF ANTIVIRALS

  摘要：

  本发明涉及具有CYP450抑制特性的化合物，因此可用作某些药物的增效剂，即当与某些药物联合给药时能够增加至少一种药代动力学变量。该发明还提供了所述化合物用作提高某些药物生物利用度的方法。本发明还提供了所述化合物的制备方法和药物组合物。

  公开号：

  US20100305073A1
• 作为产物：
  描述：

  4-氨基-3-羟基苯甲酸甲酯 在 吡啶 、 三甲基氯硅烷 、 水 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 sodium iodide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 26.0h， 生成 N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-2-(ethyl(methyl)amino)-N-isobutylbenzo[d]oxazole-6-carboxamide
  参考文献：
  名称：

  Benzoxazole and benzothiazole amides as novel pharmacokinetic enhancers of HIV protease inhibitors

  摘要：

  A new class of benzoxazole and benzothiazole amide derivatives exhibiting potent CYP3A4 inhibiting properties was identified. Extensive lead optimization was aimed at improving the CYP3A4 inhibitory properties as well as overall ADME profile of these amide derivatives. This led to the identification of thiazol-5-ylmethyl (2S,3R)-4-(2-(ethyl(methyl) amino)-N-isobutylbenzo[d]oxazole-6-carboxamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate (C1) as a lead candidate for this class. This compound together with structurally similar analogues demonstrated excellent 'boosting' properties when tested in dogs. These findings warrant further evaluation of their properties in an effort to identify valuable alternatives to Ritonavir as pharmacokinetic enhancers. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.022

文献信息

• EP2235008B1
  申请人：——

  公开号：EP2235008B1

  公开（公告）日：2016-03-16
• US8350048B2
  申请人：——

  公开号：US8350048B2

  公开（公告）日：2013-01-08
• [EN] AMIDE COMPOUNDS AS BOOSTERS OF ANTIVIRALS<br/>[FR] COMPOSÉS AMIDÉS COMME RENFORÇATEURS DE MÉDICAMENTS ANTIVIRAUX
  申请人：TIBOTEC PHARM LTD

  公开号：WO2009071650A2

  公开（公告）日：2009-06-11

  The present invention relates to compounds that have CYP450 inhibiting properties and are therefore useful as boosters of certain drugs, i.e. they are able to increase at least one of the pharmacokinetic variables of certain drugs when co-administered. The invention further provides the use of said compounds as improvers of the bioavailability of certain drugs. Methods for the preparation of the compounds of the invention and pharmaceutical compositions are also provided.
• AMIDE COMPOUNDS AS BOOSTERS OF ANTIVIRALS
  申请人：Jonckers Tim Hugo Maria

  公开号：US20100305073A1

  公开（公告）日：2010-12-02

  The present invention relates to compounds that have CYP 450 inhibiting properties and are therefore useful as boosters of certain drugs, i.e. they are able to increase at least one of the pharmacokinetic variables of certain drugs when co-administered. The invention further provides the use of said compounds as improvers of the bioavailability of certain drugs. Methods for the preparation of the compounds of the invention and pharmaceutical compositions are also provided.

  本发明涉及具有CYP450抑制特性的化合物，因此可用作某些药物的增效剂，即当与某些药物联合给药时能够增加至少一种药代动力学变量。该发明还提供了所述化合物用作提高某些药物生物利用度的方法。本发明还提供了所述化合物的制备方法和药物组合物。
• Benzoxazole and benzothiazole amides as novel pharmacokinetic enhancers of HIV protease inhibitors
  作者：Tim H.M. Jonckers、Marie-Claude Rouan、Geerwin Haché、Wim Schepens、Sabine Hallenberger、Judith Baumeister、Jennifer C. Sasaki

  DOI：10.1016/j.bmcl.2012.06.022

  日期：2012.8

  A new class of benzoxazole and benzothiazole amide derivatives exhibiting potent CYP3A4 inhibiting properties was identified. Extensive lead optimization was aimed at improving the CYP3A4 inhibitory properties as well as overall ADME profile of these amide derivatives. This led to the identification of thiazol-5-ylmethyl (2S,3R)-4-(2-(ethyl(methyl) amino)-N-isobutylbenzo[d]oxazole-6-carboxamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate (C1) as a lead candidate for this class. This compound together with structurally similar analogues demonstrated excellent 'boosting' properties when tested in dogs. These findings warrant further evaluation of their properties in an effort to identify valuable alternatives to Ritonavir as pharmacokinetic enhancers. (c) 2012 Elsevier Ltd. All rights reserved.