(+)-(6R)-2,6-二氨基-4,5,6,7-四氢苯并噻唑 | 106092-11-9

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: (+)-(6R)-2,6-二氨基-4,5,6,7-四氢苯并噻唑
• 中文别名: R-2,6-二氨基-4,5,6,7-四氢苯并噻唑；(+)-2,6-氨基-4,5,6,7-四氢苯并噻唑；R-(+)-2,6-二氨基-4,5,6,7-四氢苯并噻唑；(R)-2,6-二氨基-4,5,6,7-四氢苯并噻唑；(6R)-2,6-二氨基-4,5,6,7-四氢苯并噻唑
• 英文名称: (R)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine
• 英文别名: (R)-4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-2,6-diamine；(R)-4,5,6,7-Tetrahydro-benzothiazole-2,6-diamine；(6R)-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
• CAS: 106092-11-9
• 化学式: C₇H₁₁N₃S
• 分子量: 169.25
• InChiKey: DRRYZHHKWSHHFT-SCSAIBSYSA-N

物化性质

• 熔点：
  228-230°C
• 沸点：
  359.0±42.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于甲醇（少量）、水（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (+)-(6R)-2,6-二氨基-4,5,6,7-四氢苯并噻唑 在 盐酸 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 2-甲基四氢呋喃 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 1.33h， 生成 (R)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine dihydrochloride
  参考文献：
  名称：

  [EN] IMPROVED SYNTHESIS OF AMINE SUBSTITUTED 4,5,6,7-TETRAHYDROBENZOTHIAZOLE COMPOUNDS
  [FR] SYNTHÈSE AMÉLIORÉE DE COMPOSÉS SUBSTITUÉS PAR AMINE DE 4,5,6,7-TÉTRAHYDROBENZOTHIAZOLE

  摘要：

  本发明涉及一种改进的方法，用于制备公式I的氨基取代的4,5,6,7-四氢苯并噻唑化合物，例如化合物2-氨基-4,5,6,7-四氢-6-(n-丙基氨基)苯并噻唑。本发明还涉及(R)-2-氨基-4,5,6,7-四氢-6-(n-丙基氨基)苯并噻唑的改进合成方法。本发明还涉及与合成过程相关的方法和中间体。

  公开号：

  WO2013096816A1
• 作为产物：
  描述：

  6-乙酰胺基-2-氨基-4,5,6,7-四氢苯并噻唑 在 D-酒石酸 、 氢溴酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 (+)-(6R)-2,6-二氨基-4,5,6,7-四氢苯并噻唑
  参考文献：
  名称：

  Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site

  摘要：

  Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coil DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo [1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coil DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coil topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and Delta tolC E. coil strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

  DOI：

  10.1021/acs.jmedchem.5b00489

文献信息

• On-Chip Screening of a Glycomimetic Library with C-Type Lectins Reveals Structural Features Responsible for Preferential Binding of Dectin-2 over DC-SIGN/R and Langerin
  作者：Laura Medve、Silvia Achilli、Sonia Serna、Fabio Zuccotto、Norbert Varga、Michel Thépaut、Monica Civera、Corinne Vivès、Franck Fieschi、Niels Reichardt、Anna Bernardi

  DOI：10.1002/chem.201802577

  日期：2018.9.25

  A library of mannose‐ and fucose‐based glycomimetics was synthesized and screened in a microarray format against a set of C‐type lectin receptors (CLRs) that included DC‐SIGN, DC‐SIGNR, langerin, and dectin‐2. Glycomimetic ligands able to interact with dectin‐2 were identified for the first time. Comparative analysis of binding profiles allowed their selectivity against other CLRs to be probed.

  合成了一个基于甘露糖和岩藻糖的糖模拟物库，并以微阵列格式针对一组包括DC-SIGN，DC-SIGNR，Langerin和dectin-2的C型凝集素受体（CLR）进行了筛选。首次鉴定出能够与dectin-2相互作用的拟模拟配体。结合概况的比较分析允许探测其对其他CLR的选择性。
• HEPATITIS B CAPSID ASSEMBLY MODULATORS
  申请人：VenatoRx Pharmaceuticals, Inc.

  公开号：US20190375708A1

  公开（公告）日：2019-12-12

  Described herein are hepatitis B capsid assembly modulators and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of hepatitis B.

  本文描述了乙型肝炎胶囊组装调节剂和包含该类化合物的药物组合物。这些化合物和组合物对于治疗乙型肝炎是有用的。
• Design, synthesis and biological evaluation of 4,5-dibromo-N-(thiazol-2-yl)-1H-pyrrole-2-carboxamide derivatives as novel DNA gyrase inhibitors
  作者：Tihomir Tomašič、Matic Mirt、Michaela Barančoková、Janez Ilaš、Nace Zidar、Päivi Tammela、Danijel Kikelj

  DOI：10.1016/j.bmc.2016.10.038

  日期：2017.1

  clinic. In the present study, two new series of Escherichia coli DNA gyrase inhibitors bearing the 4,5-dibromopyrrolamide moiety have been designed and synthesized. 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazole-2,6-diamine derivatives inhibited E. coli DNA gyrase in the submicromolar to low micromolar range (IC50 values between 0.891 and 10.4μM). Their "ring-opened" analogues, based on the 2-(2-aminothiazol-4-yl)acetic

  新型DNA促旋酶B抑制剂的开发是抗菌药物发现的重要领域，其目的是将这种机制类别的更有效的代表引入临床。在本研究中，已设计并合成了两个带有4,5-二溴吡咯酰胺部分的新系列大肠杆菌DNA促旋酶抑制剂。4,5,6,7-四氢苯并[1,2-d]噻唑-2,6-二胺衍生物可在亚微摩尔至低微摩尔范围内抑制大肠杆菌DNA促旋酶（IC50值在0.891至10.4μM之间）。他们基于2-（2-氨基噻唑-4-基）乙酸支架的“开环”类似物显示出较弱的DNA旋转酶抑制作用，IC50值为15.9至169μM。进行分子对接实验以研究抑制剂的结合模式。
• [EN] SYNTHESIS OF CHIRALLY PURIFIED SUBSTITUTED BENZOTHIAZOLE DIAMINES<br/>[FR] SYNTHÈSE DE BENZOTHIAZOLE-DIAMINES SUBSTITUÉES PURIFIÉES CHIRALEMENT
  申请人：KNOPP NEUROSCIENCES

  公开号：WO2011109596A1

  公开（公告）日：2011-09-09

  Methods for preparing chirally purified substituted 4,5,6,7-tetrahydro-benzotiazole diamines such as, for example, (6R)2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole and purifying a dominant enantiomer of substituted 4,5,6,7-tetrahydro-benzotiazole diamines from entantiomerically enriched mixtures of substituted 4,5,6,7-tetrahydro-benzotiazole diamines are provided herein.

  本文提供了制备手性纯净的取代4,5,6,7-四氢苯并噻唑二胺的方法，例如（6R）-2-氨基-4,5,6,7-四氢-6-(丙基氨基)苯并噻唑，并从手性富集的取代4,5,6,7-四氢苯并噻唑二胺混合物中提纯取代4,5,6,7-四氢苯并噻唑二胺的主对映体。
• Novel pyrazinone and pyridinone thrombin inhibitors incorporating weakly basic heterobicyclic P1-arginine mimetics
  作者：Andreja Kranjc、Lucija Peterlin Mašič、Sebastjan Reven、Klemen Mikic、Andrej Preželj、Mojca Stegnar、Danijel Kikelj

  DOI：10.1016/j.ejmech.2005.03.007

  日期：2005.8

  The design, synthesis and biological activity of new thrombin inhibitors with a pyridinone or pyrazinone core and different heterobicyclic P(1) arginine side-chain mimetics are described. The arginine side-chain mimetics used in this study are (+/-)-4,5,6,7-tetrahydro-2H-indazol-5-ylmethanamine and both enantiomers thereof, (+/-)-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine and the corresponding

  设计，合成和生物活性的新型凝血酶抑制剂具有吡啶酮或吡嗪酮核心和不同的杂环双（P）（1）精氨酸侧链模拟物。在这项研究中使用的精氨酸侧链模拟物是（+/-）-4,5,6,7-四氢-2H-吲唑-5-基甲胺及其两种对映体（+/-）-4,5,6 ，7-四氢-1，3-苯并噻唑-2，6-二胺和相应的R对映体。吡嗪酮系列抑制剂中最有效的化合物25在体外的K（i）为41 nM，对胰蛋白酶和Xa因子的选择性高。