5,5-二甲基-2-(哌嗪-1-基)-4,5-二氢噻唑 | 303798-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 5,5-二甲基-2-(哌嗪-1-基)-4,5-二氢噻唑
• 英文名称: 5,5-dimethyl-2-(piperazin-1-yl)-2,5-dihydrothiazole
• 英文别名: 5,5-dimethyl-2-(piperazin-1-yl)-4,5-dihydrothiazole；5,5-dimethyl-2-piperazin-1-yl-4H-1,3-thiazole
• CAS: 303798-21-2
• 化学式: C₉H₁₇N₃S
• mdl: MFCD00573078
• 分子量: 199.32
• InChiKey: BKUDSGWZPKYESY-UHFFFAOYSA-N

物化性质

• 沸点：
  300.7±52.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.888
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  5,5-二甲基-2-(哌嗪-1-基)-4,5-二氢噻唑 、 4-氯-6-乙基噻吩并[2,3-d]嘧啶 在 N,N-二异丙基乙胺 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 4-[4-(5,5-dimethyl-4H-1,3-thiazol-2-yl)piperazin-1-yl]-6-ethylthieno[2,3-d]pyrimidine;hydrochloride
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR TREATMENT OF LEUKEMIA
  [FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA LEUCÉMIE

  摘要：

  本发明涉及有效治疗白血病的方法。具体而言，本发明提供了抑制Menin与MLL和MLL融合癌基因蛋白相互作用的组合物和方法，以及筛选这些组合物的系统和方法。

  公开号：

  WO2011029054A1
• 作为产物：
  描述：

  甲代烯丙基异硫氰酸酯 、 N-Boc-哌嗪 在 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以382 mg的产率得到5,5-二甲基-2-(哌嗪-1-基)-4,5-二氢噻唑
  参考文献：
  名称：

  US2014/275070

  摘要：

  公开号：

文献信息

• [EN] COMPOSITIONS COMPRISING THIENOPYRIMIDINE AND THIENOPYRIDINE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSITIONS COMPRENANT DES COMPOSÉS THIÉNOPYRIMIDINE ET THIÉNOPYRIDINE ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：UNIV MICHIGAN

  公开号：WO2014164543A1

  公开（公告）日：2014-10-09

  The present invention relates generally to thienopyrimidine and thienopyridine class compounds and methods of use thereof. In particular embodiments, the present invention provides compositions comprising thienopyrimidine and thienopyridine class compounds and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins (e.g., for the treatment of leukemia, solid cancers and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin).

  本发明通常涉及噻吩嘧啶和噻吩吡啶类化合物及其使用方法。在特定实施例中，本发明提供包含噻吩嘧啶和噻吩吡啶类化合物的组合物和使用方法，以抑制Menin与MLL1、MLL2和MLL融合癌基因蛋白的相互作用（例如，用于治疗白血病、实体肿瘤和其他依赖于MLL1、MLL2、MLL融合蛋白和/或Menin活性的疾病）。
• COMPOSITIONS COMPRISING THIENOPYRIMIDINE AND THIENOPYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20160046647A1

  公开（公告）日：2016-02-18

  The present invention relates generally to thienopyrimidine and thienopyridine class compounds and methods of use thereof. In particular embodiments, the present invention provides compositions comprising thienopyrimidine and thienopyridine class compounds and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins (e.g., for the treatment of leukemia, solid cancers and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin).

  本发明涉及噻吩嘧啶和噻吩啶类化合物及其使用方法。在特定实施例中，本发明提供包含噻吩嘧啶和噻吩啶类化合物的组合物以及使用方法，以抑制Menin与MLL1、MLL2和MLL融合癌蛋白的相互作用（例如，用于治疗依赖于MLL1、MLL2、MLL融合蛋白和/或Menin活性的白血病、实体癌和其他疾病）。
• Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein–Ligand Complexes
  作者：Jonathan Pollock、Dmitry Borkin、George Lund、Trupta Purohit、Edyta Dyguda-Kazimierowicz、Jolanta Grembecka、Tomasz Cierpicki

  DOI：10.1021/acs.jmedchem.5b00975

  日期：2015.9.24

  Multipolar interactions involving fluorine and the protein backbone have been frequently observed in protein ligand complexes. Such fluorine backbone interactions may substantially contribute to the high affinity of small molecule inhibitors. Here we found that introduction of trifluoromethyl groups into two different sites in the thienopyrimidine class of menin-MLL inhibitors considerably improved their inhibitory activity. In both cases, trifluoromethyl groups are engaged in short interactions with the backbone of menin. In order to understand the effect of fluorine, we synthesized a series of analogues by systematically changing the number of fluorine atoms, and we determined high-resolution crystal structures of the complexes with menin. We found that introduction of fluorine at favorable geometry for interactions with backbone carbonyls may improve the activity of menin-MLL inhibitors as much as 5- to 10-fold. In order to facilitate the design of multipolar fluorine backbone interactions in protein ligand complexes, we developed a computational algorithm named FMAP, which calculates fluorophilic sites in proximity to the protein backbone. We demonstrated that FMAP could be used to rationalize improvement in the activity of known protein inhibitors upon introduction of fluorine. Furthermore, FMAP may also represent a valuable tool for designing new fluorine substitutions and support ligand optimization in drug discovery projects. Analysis of the menin-MLL inhibitor complexes revealed that the backbone in secondary structures is particularly accessible to the interactions with fluorine. Considering that secondary structure elements are frequently exposed at protein interfaces, we postulate that multipolar fluorine backbone interactions may represent a particularly attractive approach to improve inhibitors of protein protein interactions.
• US20140275070A1
  申请人：——

  公开号：US20140275070A1

  公开（公告）日：2014-09-18
• US9216993B2
  申请人：——

  公开号：US9216993B2

  公开（公告）日：2015-12-22