CAY10581 | 1062318-05-1

• 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: CAY10581
• 英文别名: (3S,4S)-4-benzylamino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione；(3S,4S)-4-(Benzylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydrobenzo[g]chromene-5,10-dione
• CAS: 1062318-05-1
• 化学式: C₂₂H₂₁NO₄
• 分子量: 363.413
• InChiKey: WKHJQIQDQXGUOD-UWJYYQICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  苄胺 、 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53%的产率得到CAY10581
  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

• METHOD OF BLOCKING TRANSMISSION OF MALARIAL PARASITE
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERV

  公开号：US20160264570A1

  公开（公告）日：2016-09-15

  The invention provides a method of blocking transmission of a Plasmodium parasite and a method of treating or preventing malaria comprising administering to an animal an effective amount of a first compound of formula I: wherein A, B, R 1 , R 2 , R 10 , and R 11 are described herein, either alone or in combination with a second compound selected from elesclomol, NSC 174938, NVP-AUY922, Maduramicin, Narasin, Alvespimycin, Omacetaxine, Thiram, Zinc pyrithione, Phanquinone, Bortezomib, Salinomycin sodium, Monensin sodium, Dipyrithione, Dicyclopentamethylene-thiuram disulfide, YM155, Withaferin A, Adriamycin, Romidepsin, AZD-1 152-HQPA, CAY10581, Plicamycin, CUDC-101, Auranofin, Trametinib, GSK-458, Afatinib, and Panobinostat.

  本发明提供了一种阻止疟原虫传播的方法和一种治疗或预防疟疾的方法，包括向动物施用公式I的第一化合物的有效量，其中A、B、R1、R2、R10和R11如本文所述，可以单独使用或与从elesclomol、NSC 174938、NVP-AUY922、Maduramicin、Narasin、Alvespimycin、Omacetaxine、Thiram、Zinc pyrithione、Phanquinone、Bortezomib、Salinomycin sodium、Monensin sodium、Dipyrithione、Dicyclopentamethylene-thiuram disulfide、YM155、Withaferin A、Adriamycin、Romidepsin、AZD-1 152-HQPA、CAY10581、Plicamycin、CUDC-101、Auranofin、Trametinib、GSK-458、Afatinib和Panobinostat中选择的第二化合物组合使用。
• 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.