(3S,4S)-4-butylamino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione | 1018340-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: (3S,4S)-4-butylamino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione
• 英文别名: (3S,4S)-4-(butylamino)-3-hydroxy-2,2-dimethyl-2H,3H,4H,5H,10H-naphtho[2,3-b]pyran-5,10-dione；(3S,4S)-4-(butylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydrobenzo[g]chromene-5,10-dione
• CAS: 1018340-11-8
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: PWJHHLDOTFKWMM-KSSFIOAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  正丁胺 、 2,2-dimethyl-3,4-epoxy-2H-naphtho[2,3-b]pyran-5,10-dione 在 indium(III) chloride 作用下， 以 二氯甲烷 为溶剂， 以58%的产率得到(3S,4S)-4-butylamino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione
  参考文献：
  名称：

  Indoleamine 2,3-Dioxygenase Is the Anticancer Target for a Novel Series of Potent Naphthoquinone-Based Inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K-i = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation.

  DOI：

  10.1021/jm7014155

文献信息

• NOVEL IDO INHIBITORS AND METHODS OF USE THEREOF
  申请人：Lankenau Institute for Medical Research

  公开号：EP2137168B1

  公开（公告）日：2016-09-14
• Novel IDO Inhibitors and Methods of Use Thereof
  申请人：Prendergast George C.

  公开号：US20100076066A1

  公开（公告）日：2010-03-25

  Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.
• US8389568B2
  申请人：——

  公开号：US8389568B2

  公开（公告）日：2013-03-05
• [EN] NOVEL IDO INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] NOUVEAUX INHIBITEURS IDO ET LEURS PROCÉDÉS D'UTILISATION
  申请人：LANKENAU INST MEDICAL RES

  公开号：WO2008115804A1

  公开（公告）日：2008-09-25

  [EN] Novel indolearaine 2, 3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.
  [FR] L'invention concerne de nouveaux inhibiteurs de 2,3-dioxygénase d'indoléaraine (IDO), des compositions les contenant et leurs procédés d'utilisation.
• Indoleamine 2,3-Dioxygenase Is the Anticancer Target for a Novel Series of Potent Naphthoquinone-Based Inhibitors
  作者：Sanjeev Kumar、William P. Malachowski、James B. DuHadaway、Judith M. LaLonde、Patrick J. Carroll、Daniel Jaller、Richard Metz、George C. Prendergast、Alexander J. Muller

  DOI：10.1021/jm7014155

  日期：2008.3.1

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K-i = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation.