8-(6-(dimethylamino)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine | 1289555-31-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 8-(6-(dimethylamino)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine
• 英文别名: 8-[[6-(dimethylamino)-1,3-benzodioxol-5-yl]sulfanyl]-7H-purin-6-amine
• CAS: 1289555-31-2
• 化学式: C₁₄H₁₄N₆O₂S
• 分子量: 330.37
• InChiKey: WSXYQBWLHVAVQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-(6-(dimethylamino)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine 在 caesium carbonate 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-(3-(6-amino-8-(6-(dimethylamino)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-9-yl)propyl)cyclopropanecarboxamide
  参考文献：
  名称：

  [EN] HSP90 INHIBITORS
  [FR] INHIBITEURS DE LA HSP90

  摘要：

  公开号：

  WO2012138894A4
• 作为产物：
  描述：

  6-碘-N,N-二甲基苯并[D][1,3]二氧杂环戊烯-5-胺 、 8-巯基腺嘌呤 在 copper(l) iodide 、 2,9-dimethyl-1,10-phenanthroline hydrate 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 以39%的产率得到8-(6-(dimethylamino)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine
  参考文献：
  名称：

  Structure–Activity Relationship in a Purine-Scaffold Compound Series with Selectivity for the Endoplasmic Reticulum Hsp90 Paralog Grp94

  摘要：

  Grp94 is involved in the regulation of a restricted number of proteins and represents a potential target in a host of diseases, including cancer, septic shock, autoimmune diseases, chronic inflammatory conditions, diabetes, coronary thrombosis, and stroke. We have recently identified a novel allosteric pocket located in the Grp94 N-terminal binding site that can be used to design ligands with a 2-log selectivity over the other Hsp90 paralogs. Here we perform extensive SAR investigations in this ligand series and rationalize the affinity and paralog selectivity of choice derivatives by molecular modeling. We then use this to design 18c, a derivative with good potency for Grp94 (IC50 = 0.22 mu M) and selectivity over other paralogs (>100- and 33-fold for Hsp90 alpha/beta and Trap-1, respectively). The paralog selectivity and target-mediated activity of 18c was confirmed in cells through several functional readouts. Compound 18c was also inert when tested against a large panel of kinases. We show that 18c has biological activity in several cellular models of inflammation and cancer and also present here for the first time the in vivo profile of a Grp94 inhibitor.

  DOI：

  10.1021/acs.jmedchem.5b00197

文献信息

• [EN] PURINE DERIVATIVES USEFUL AS HSP90 INHIBITORS<br/>[FR] DÉRIVÉS DE PURINE CONVENANT COMME INHIBITEURS DE HSP90
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2011044394A1

  公开（公告）日：2011-04-14

  The present application provides substituted purine derivatives and related compounds of the formulas shown. These com ounds are useful as inhibitors of HSP90, and hence in the treatment of related diseases. (Formulae) Z1-Z3, Xa-Xc, X2, X4, Y and R are as defined in the specification.

  本申请提供所示公式的取代嘌呤衍生物及相关化合物。这些化合物作为HSP90抑制剂具有用途，因此可用于治疗相关疾病。（公式）Z1-Z3、Xa-Xc、X2、X4、Y和R的定义见说明书。
• Hsp90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20120208806A1

  公开（公告）日：2012-08-16

  The present application provides compounds useful in the inhibition of Hsp90, and hence in the treatment of disease.

  本申请提供了一些化合物，可用于抑制Hsp90，并因此用于治疗疾病。
• HSP90 Inhibitors
  申请人：Taldone Tony

  公开号：US20140045867A1

  公开（公告）日：2014-02-13

  The disclosure relates to Compounds of Formula (1) : and pharmaceutically acceptable salts thereof wherein Z 1 , Z 2 , Z 3 , Xa, Xb, Xc, Y, X 2 , and X 4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof, and methods to treat or prevent a condition, such as cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof.

  本公开涉及式（1）的化合物及其药学上可接受的盐，其中Z1，Z2，Z3，Xa，Xb，Xc，Y，X2和X4的定义如本文所述，包括有效量的式（1）化合物或其药学上可接受的盐的组合物，以及治疗或预防一种疾病的方法，例如癌症，该疾病过度表达Her-kinases，该方法包括向需要治疗的患者施用式（1）化合物或其药学上可接受的盐的治疗有效量。
• HSP90 COMBINATION THERAPY
  申请人：Chiosis Gabriela

  公开号：US20140315929A1

  公开（公告）日：2014-10-23

  This invention concerns a method for selecting an inhibitor of a cancer-implicated pathway or of a component of a cancer-implicated pathway for coadministration, with an inhibitor of HSP90, to a subject suffering from a cancer which comprises the following steps: (a) contacting a sample containing cancer cells from a subject with an inhibitor of HSP90 or an analog, homolog or derivative of an inhibitor of HSP90 under conditions such that one or more cancer pathway components present in the sample bind to the HSP90 inhibitor or the analog, homolog or derivative of the HSP90 inhibitor; (b) detecting pathway components bound to the HSP90 inhibitor or to the analog, homolog or derivative of the HSP90 inhibitor; (c) analyzing the pathway components detected in step (b) so as to identify a pathway which includes the components detected in step (b) and additional components of such pathway; and (d) selecting an inhibitor of the pathway or of a pathway component identified in step (c). This invention further concerns a method of treating a cancer patient by coadministering an inhibitor of HSP90 and an inhibitor of a cancer-implicated pathway or component thereof.

  本发明涉及一种选择癌症相关通路或癌症相关通路组分的抑制剂的方法，用于与HSP90的抑制剂一起共同治疗患有癌症的受试者，包括以下步骤：(a)将含有受试者的癌细胞的样本与HSP90抑制剂或其类似物、同源物或衍生物接触，以使样本中的一个或多个癌症通路组分与HSP90抑制剂或其类似物、同源物或衍生物结合；(b)检测与HSP90抑制剂或其类似物、同源物或衍生物结合的通路组分；(c)分析在步骤(b)中检测到的通路组分，以识别包括步骤(b)中检测到的组分和该通路的其他组分的通路；(d)选择通路或步骤(c)中识别的通路组分的抑制剂。本发明还涉及一种通过共同给予HSP90抑制剂和癌症相关通路或其组分的抑制剂来治疗癌症患者的方法。
• HSP90 INHIBITORS
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：US20160264577A1

  公开（公告）日：2016-09-15

  The disclosure relates to Compounds of Formulae (IA) and (IB), and pharmaceutically acceptable salts thereof wherein Z 1 , Z 2 , Z 3 , Xa, Xb, Xc, Xd, Y, X 2 , and X 4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (IA) and/or (IB), and methods to treat or prevent a condition, such cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (IA) or (IB). The disclosure further relates to compounds of Formulae (IA) and (IB) in which X 2 is a leaving for introducing a radiolabeled atom, such as 124 I or 131 I and to methods of using such compounds in the preparation of radiolabeled compounds, particularly for use in imaging.

  本公开涉及式（IA）和（IB）的化合物及其药学上可接受的盐，其中Z1、Z2、Z3、Xa、Xb、Xc、Xd、Y、X2和X4的定义如本文所述，包含有效量的式（IA）和/或（IB）化合物的组合物，以及治疗或预防过度表达Her-kinases的癌症等疾病的方法，包括向需要治疗的患者施用式（IA）或（IB）化合物的治疗有效量。本公开还涉及式（IA）和（IB）的化合物，其中X2是引入放射性标记原子（如124I或131I）的离去基团，以及使用这种化合物制备放射性标记化合物的方法，特别是用于成像。