2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-oxazol-4-yl}-ethanol | 876616-89-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-oxazol-4-yl}-ethanol
• 英文别名: 2-[5-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-oxazol-4-yl]ethanol
• CAS: 876616-89-6
• 化学式: C₁₈H₂₄BNO₄
• 分子量: 329.204
• InChiKey: XJVXOBPMPAYQSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-oxazol-4-yl}-ethanol 在 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 TEA 、 caesium carbonate 、 cesium fluoride 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(2-(Isopropoxycarbonylamino-methyl)-4-{2-[5-methyl-2-(4-pyrimidin-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands

  摘要：

  PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.011
• 作为产物：
  描述：

  联硼酸频那醇酯 、 2-[2-(4-溴苯基)-5-甲基-1,3-恶唑-4-基]乙醇 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-oxazol-4-yl}-ethanol
  参考文献：
  名称：

  [EN] OXAZOLE DERIVATIVES AS HISTAMINE H3 RECEPTOR AGENTS, PREPARATION AND THERAPEUTIC USES
  [FR] DERIVES D'OXAZOLE EN TANT QU'AGENTS DE RECEPTEUR D'HISTAMINE H3, PREPARATION ET UTILISATIONS THERAPEUTIQUES

  摘要：

  本发明公开了具有组分I（I）的新型芳基噁唑化合物或其药学上可接受的盐，其具有组胺H3受体拮抗剂或逆向激动剂活性，以及制备和使用这些化合物的方法。在另一实施方案中，本发明公开了包括组分I化合物的药物组合物，以及使用这些组合物治疗肥胖、认知缺陷、嗜睡症和其他组胺H3受体相关疾病的方法。组分I（I）或其药学上可接受的盐，其中：m在每次出现时独立地为1、2或3，Z独立地表示碳（用氢或此处指示的可选取代基团取代）或氮，但当Z为氮时，R6不连接到Z；R1和R2独立地为-(C1-C7)烷基（可选地用一到三个卤素取代），或者R1和R2以及它们连接的氮形成氮杂环戊二烷环、吡咯环或哌啶环，进一步地，所形成的氮杂环戊二烷、吡咯环或哌啶环可以用R5取代一到三次；R6在每次出现时独立地为-H、-卤素或-CH3。

  公开号：

  WO2006019833A1

文献信息

• [EN] OXAZOLE DERIVATIVES AS HISTAMINE H3 RECEPTOR AGENTS, PREPARATION AND THERAPEUTIC USES<br/>[FR] DERIVES D'OXAZOLE EN TANT QU'AGENTS DE RECEPTEUR D'HISTAMINE H3, PREPARATION ET UTILISATIONS THERAPEUTIQUES
  申请人：LILLY CO ELI

  公开号：WO2006019833A1

  公开（公告）日：2006-02-23

  The present invention discloses novel aryl oxazole compounds of Formula I (I), or pharmaceutically acceptable salts thereof, which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods for preparing and using such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using these compositions to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases. Formula I (I) or a pharmaceutically acceptable salt thereof, wherein: m is independenlly at each occurrence 1, 2, or 3, Z independently represents carbon (substituted with hydrogen or the optional substituents indicated herein) or nitrogen, provided that when Z is nitrogen then R6 is not attached to Z; R1 and R2 are independently -(C1-C7) alkyl(optionally substituted with one to three halogens), or R1 and R2 and the nitrogen to which they are attached form an azetidinyl ring, a pyrrolidinyl ring, or a piperidinyl ring, wherein further the azetidinyl, pyrrolidinyl, or piperidinyl ring so formed may be optionally substituted one to three times with R5; R6 is independently at each occurrence -H, -halogen, or -CH3.

  本发明公开了具有组分I（I）的新型芳基噁唑化合物或其药学上可接受的盐，其具有组胺H3受体拮抗剂或逆向激动剂活性，以及制备和使用这些化合物的方法。在另一实施方案中，本发明公开了包括组分I化合物的药物组合物，以及使用这些组合物治疗肥胖、认知缺陷、嗜睡症和其他组胺H3受体相关疾病的方法。组分I（I）或其药学上可接受的盐，其中：m在每次出现时独立地为1、2或3，Z独立地表示碳（用氢或此处指示的可选取代基团取代）或氮，但当Z为氮时，R6不连接到Z；R1和R2独立地为-(C1-C7)烷基（可选地用一到三个卤素取代），或者R1和R2以及它们连接的氮形成氮杂环戊二烷环、吡咯环或哌啶环，进一步地，所形成的氮杂环戊二烷、吡咯环或哌啶环可以用R5取代一到三次；R6在每次出现时独立地为-H、-卤素或-CH3。
• Oxazole derivatives as histamine h3 receptor agents,preparation and therapeutic uses
  申请人：Beavers Selsam Lisa

  公开号：US20070197604A1

  公开（公告）日：2007-08-23

  The present invention discloses novel aryl oxazole compounds of Formula I (I), or pharmaceutically acceptable salts thereof, which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods for preparing and using such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using these compositions to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases. Formula I (I) or a pharmaceutically acceptable salt thereof, wherein: m is independenlly at each occurrence 1, 2, or 3, Z independently represents carbon (substituted with hydrogen or the optional substituents indicated herein) or nitrogen, provided that when Z is nitrogen then R6 is not attached to Z; R1 and R2 are independently —(C 1 —C 7 ) alkyl (optionally substituted with one to three halogens), or R1 and R2 and the nitrogen to which they are attached form an azetidinyl ring, a pyrrolidinyl ring, or a piperidinyl ring, wherein further the azetidinyl, pyrrolidinyl, or piperidinyl ring so formed may be optionally substituted one to three times with R5; R6 is independently at each occurrence —H, -halogen, or —CH 3 .

  本发明披露了式I（I）的新型芳基噁唑化合物或其药学上可接受的盐，具有组胺H3受体拮抗剂或反向激动剂活性，以及制备和使用这些化合物的方法。在另一实施例中，本发明披露了包含式I化合物的药物组合物，以及使用这些组合物治疗肥胖症、认知缺陷、嗜睡病和其他组胺H3受体相关疾病的方法。其中，式I（I）或其药学上可接受的盐，其中：m在每次出现时独立地为1、2或3，Z独立地表示碳（用氢或此处指示的可选取代基替换）或氮，但当Z为氮时，R6不与Z连接；R1和R2独立地为—（C1-C7）烷基（可选取代有1至3个卤素），或R1和R2以及它们所连接的氮形成一个氮杂环、吡咯烷环或哌啶环，其中进一步形成的氮杂环、吡咯烷环或哌啶环可以用R5取代1至3次；R6在每次出现时独立地为—H、-卤素或—CH3。
• Oxazole derivatives as histamine H3 receptor agents, preparation and therapeutic uses
  申请人：Eli Lilly and Company

  公开号：US07666871B2

  公开（公告）日：2010-02-23

  The present invention discloses novel aryl oxazole compounds of Formula I (I), or pharmaceutically acceptable salts thereof, which have histamine-H3 receptor antagonist or inverse agonist activity, as well as methods for preparing and using such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using these compositions to treat obesity, cognitive deficiencies, narcolepsy, and other histamine H3 receptor-related diseases. Formula I (I) or a pharmaceutically acceptable salt thereof, wherein: m is independenlly at each occurrence 1, 2, or 3, Z independently represents carbon (substituted with hydrogen or the optional substituents indicated herein) or nitrogen, provided that when Z is nitrogen then R6 is not attached to Z; R1 and R2 are independently —(C1—C7) alkyl (optionally substituted with one to three halogens), or R1 and R2 and the nitrogen to which they are attached form an azetidinyl ring, a pyrrolidinyl ring, or a piperidinyl ring, wherein further the azetidinyl, pyrrolidinyl, or piperidinyl ring so formed may be optionally substituted one to three times with R5; R6 is independently at each occurrence —H, -halogen, or —CH3.

  本发明揭示了新颖的芳基噁唑化合物，其化学式为I（I），或其药学上可接受的盐，具有组胺H3受体拮抗剂或反式激动剂活性，以及制备和使用这种化合物的方法。在另一实施方案中，本发明揭示了包括化合物I的药物组合物，以及使用这些组合物治疗肥胖症、认知缺陷、嗜睡症和其他组胺H3受体相关疾病的方法。其中，化合物I（I）或其药学上可接受的盐，其中：m在每个出现的位置上独立地为1、2或3，Z独立地表示碳（用氢或本文所示的可选取代基取代）或氮，但当Z为氮时，R6不与Z连接；R1和R2独立地为—（C1-C7）烷基（可选取代有一到三个卤素），或R1和R2及它们所连接的氮形成一个氮杂环、吡咯烷环或哌啶环，其中进一步形成的氮杂环、吡咯烷环或哌啶环可以用R5取代一到三次；R6在每个出现的位置上独立地为—H、-卤素或—CH3。
• Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands
  作者：Alan M. Warshawsky、Charles A. Alt、Joseph T. Brozinick、Allen R. Harkness、Eric D. Hawkins、James R. Henry、Donald P. Matthews、Anne R. Miller、Elizabeth A. Misener、Chahrzad Montrose-Rafizadeh、Gary A. Rhodes、Quanrong Shen、Jennifer A. Vance、Uko E. Udodong、Minmin Wang、Tony Y. Zhang、Richard W. Zink

  DOI：10.1016/j.bmcl.2006.09.011

  日期：2006.12

  PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes. (c) 2006 Elsevier Ltd. All rights reserved.