tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)carbamate | 943323-78-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硼酸衍生物
• 英文名称: tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)carbamate
• 英文别名: 1,1-Dimethylethyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thienyl]carbamate；tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]carbamate
• CAS: 943323-78-2
• 化学式: C₁₅H₂₄BNO₄S
• 分子量: 325.237
• InChiKey: JKMJBBBJSVKAHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  85
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)carbamate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium tert-butylate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 15.0h， 生成 tert-butyl (4-(2-(benzyloxy)pyridin-3-yl)thiophen-2-yl)carbamate
  参考文献：
  名称：

  Potent and Orally Bioavailable Inverse Agonists of RORγt Resulting from Structure-Based Design

  摘要：

  Retinoic acid receptor related orphan receptor gamma t (ROR gamma t), has been identified as the master regulator of T(H)17-cell function and development, making it an attractive target for the treatment of autoimmune diseases by a small-molecule approach. Herein, we describe our investigations on a series of 4-aryl-thienyl acetamides, which were guided by insights from X-ray cocrystal structures. Efforts in targeting the cofactor-recruitment site from the 4-aryl group on the thiophene led to a series of potent binders with nanomolar activity in a primary human-T(H)17-cell assay. The observation of a DMSO molecule binding in a subpocket outside the LBD inspired the introduction of an acetamide into the benzylic position of these compounds. Hereby, a hydrogen-bond interaction of the introduced acetamide oxygen with the backbone amide of Glu379 was established. This greatly enhanced the cellular activity of previously weakly cell-active compounds. The best compounds combined potent inhibition of IL-17 release with favorable PK in rodents, with compound 32 representing a promising starting point for future investigations.

  DOI：

  10.1021/acs.jmedchem.8b00783
• 作为产物：
  描述：

  (4-溴噻吩-2-基)氨基甲酸叔丁酯 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl)carbamate
  参考文献：
  名称：

  EP2762476

  摘要：

  公开号：

文献信息

• 1,2,4-triazine-6-carboxamide derivative
  申请人：TAIHO PHARMACEUTICAL CO., LTD.

  公开号：US09145414B2

  公开（公告）日：2015-09-29

  The present invention provides a compound represented by the following general formula (I) or a salt thereof which has a Syk inhibitory effect (in the formula R1 represents a hydrogen atom or an optionally substituted C1-C6 alkyl group; A represents a hydrogen atom, an optionally substituted C1-C8 alkyl group, an optionally substituted C2-C6 alkenyl group, an optionally substituted C2-C6 alkynyl group, an optionally substituted C3-C10 cycloalkyl group, an optionally substituted C6-C14 aromatic hydrocarbon group, an optionally substituted 4- to 10-membered unsaturated heterocyclic group, or an optionally substituted 4- to 10-membered saturated heterocyclic group, or optionally forms a 4- to 10-membered unsaturated heterocyclic ring or a 4- to 10-membered saturated heterocyclic ring together with R1 and the nitrogen atom bonded thereto; R2 represents a hydrogen atom or an optionally substituted C1-C6 alkyl group; and B represents an optionally substituted unsaturated heterocyclic group).

  本发明提供了一种化合物，其通式如下（I）或其盐，具有Syk抑制作用（在公式中，R1代表氢原子或可选取代的C1-C6烷基；A代表氢原子、可选取代的C1-C8烷基、可选取代的C2-C6烯基、可选取代的C2-C6炔基、可选取代的C3-C10环烷基、可选取代的C6-C14芳香烃基、可选取代的4-至10元不饱和杂环基或可选取代的4-至10元饱和杂环基，或与R1和与其相连的氮原子一起形成4-至10元不饱和杂环环或4-至10元饱和杂环环；R2代表氢原子或可选取代的C1-C6烷基；B代表可选取代的不饱和杂环基）。
• EP2762476
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/76423
  申请人：——

  公开号：——

  公开（公告）日：——
• US20140343038A1
  申请人：——

  公开号：——

  公开（公告）日：——
• Potent and Orally Bioavailable Inverse Agonists of RORγt Resulting from Structure-Based Design
  作者：Frank Narjes、Yafeng Xue、Stefan von Berg、Jesper Malmberg、Antonio Llinas、Roine I. Olsson、Johan Jirholt、Hanna Grindebacke、Agnes Leffler、Nafizal Hossain、Matti Lepistö、Linda Thunberg、Hanna Leek、Anna Aagaard、Jane McPheat、Eva L. Hansson、Elisabeth Bäck、Stefan Tångefjord、Rongfeng Chen、Yao Xiong、Ge Hongbin、Thomas G. Hansson

  DOI：10.1021/acs.jmedchem.8b00783

  日期：2018.9.13

  Retinoic acid receptor related orphan receptor gamma t (ROR gamma t), has been identified as the master regulator of T(H)17-cell function and development, making it an attractive target for the treatment of autoimmune diseases by a small-molecule approach. Herein, we describe our investigations on a series of 4-aryl-thienyl acetamides, which were guided by insights from X-ray cocrystal structures. Efforts in targeting the cofactor-recruitment site from the 4-aryl group on the thiophene led to a series of potent binders with nanomolar activity in a primary human-T(H)17-cell assay. The observation of a DMSO molecule binding in a subpocket outside the LBD inspired the introduction of an acetamide into the benzylic position of these compounds. Hereby, a hydrogen-bond interaction of the introduced acetamide oxygen with the backbone amide of Glu379 was established. This greatly enhanced the cellular activity of previously weakly cell-active compounds. The best compounds combined potent inhibition of IL-17 release with favorable PK in rodents, with compound 32 representing a promising starting point for future investigations.