3-(4-甲基哌嗪-1-基)苯硼酸 | 1139717-76-2

• 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: 3-(4-甲基哌嗪-1-基)苯硼酸
• 中文别名: 3-(4-甲基-1-哌嗪基)苯硼酸；(3-(4-甲基哌嗪-1-基)苯基)硼酸；B-[3-(4-甲基-1-哌嗪)苯基]硼酸
• 英文名称: (3-(4-methylpiperazin-1-yl)phenyl)boronic acid
• 英文别名: 3-(4-Methyl-1-piperazinyl)phenylboronic Acid；[3-(4-methylpiperazin-1-yl)phenyl]boronic acid
• CAS: 1139717-76-2
• 化学式: C₁₁H₁₇BN₂O₂
• 分子量: 220.079
• InChiKey: HXGDRMHRVSAMGD-UHFFFAOYSA-N

物化性质

• 沸点：
  417.7±55.0 °C(Predicted)
• 密度：
  1.20

计算性质

• 辛醇/水分配系数(LogP)：
  -0.88
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  46.9
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-(4-甲基哌嗪-1-基)苯硼酸 在 tris-(dibenzylideneacetone)dipalladium(0) copper diacetate 、 caesium carbonate 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 8-fluoro-4-[5-[3-(4-methylpiperazin-1-yl)phenoxy]pyrimidin-2-yl]-3,4-dihydro-2H-benzo[1,4]oxazine
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  式（I）的化合物或其药学上可接受的盐或前药，其中X为N或CH；Q为NR6或O；A1和A2独立地为氢或C1-6烷基，或者可共同形成一个羰基团；R1和R2独立地为氢、卤素、CF3、CN、OR7、OR8、NR8R9、NR8COR10、NR8S02R10、S02NR8R9、SO2R10或C1-6烷基，可选地并独立地被一个或多个羟基、C1-6烷氧基、卤素或NR8R9取代；R3为氢、卤素、CF3或OR7；R4为氢、卤素、CF3、OR8、NR8R9、NR8COR10、NR8S02R10或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；或者当R3和R4位于邻位并共同形成-0(CH2)mO-时，其中m为1-3；R5为氢或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；R6为氢或C1-6烷基；R7为氢或C1-6烷基，可选地被OR8或NR8R9取代；R8为氢、C1-6烷基，可选地被羟基或C1-6烷氧基或C1-3烷基苯基取代，其中所述苯基可选地被一个或多个卤素、C1-6烷基、CF3、OR7、NR8R9或OCF3中的一种或多种取代基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个含有一个进一步异原子（选自NR7、S和O）的5-或6-成员环，所述5-或6-成员环可选地被羟基或C1-6烷氧基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个可选地被羟基或C1-6烷氧基取代的氮杂环戊烷环；R10为C1-6烷基或一个苯基，可选地被一个或多个卤素、C1-6烷基、CF3、OCF3或OR7中的一种或多种取代基取代；n为1或2。还公开了这些化合物在治疗淀粉样蛋白病中的用途。

  公开号：

  WO2011144578A1
• 作为产物：
  描述：

  N-甲基哌嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 正丁基锂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 生成 3-(4-甲基哌嗪-1-基)苯硼酸
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  式（I）的化合物或其药学上可接受的盐或前药，其中X为N或CH；Q为NR6或O；A1和A2独立地为氢或C1-6烷基，或者可共同形成一个羰基团；R1和R2独立地为氢、卤素、CF3、CN、OR7、OR8、NR8R9、NR8COR10、NR8S02R10、S02NR8R9、SO2R10或C1-6烷基，可选地并独立地被一个或多个羟基、C1-6烷氧基、卤素或NR8R9取代；R3为氢、卤素、CF3或OR7；R4为氢、卤素、CF3、OR8、NR8R9、NR8COR10、NR8S02R10或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；或者当R3和R4位于邻位并共同形成-0(CH2)mO-时，其中m为1-3；R5为氢或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；R6为氢或C1-6烷基；R7为氢或C1-6烷基，可选地被OR8或NR8R9取代；R8为氢、C1-6烷基，可选地被羟基或C1-6烷氧基或C1-3烷基苯基取代，其中所述苯基可选地被一个或多个卤素、C1-6烷基、CF3、OR7、NR8R9或OCF3中的一种或多种取代基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个含有一个进一步异原子（选自NR7、S和O）的5-或6-成员环，所述5-或6-成员环可选地被羟基或C1-6烷氧基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个可选地被羟基或C1-6烷氧基取代的氮杂环戊烷环；R10为C1-6烷基或一个苯基，可选地被一个或多个卤素、C1-6烷基、CF3、OCF3或OR7中的一种或多种取代基取代；n为1或2。还公开了这些化合物在治疗淀粉样蛋白病中的用途。

  公开号：

  WO2011144578A1

文献信息

• PYRIDINE DERIVATIVES FOR THE TREATMENT OF AMYLOID-RELATED DISEASES
  申请人：Scopes David Ian Carter

  公开号：US20100298325A1

  公开（公告）日：2010-11-25

  a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof: wherein X and Y are independently NR 5 or O; W and Z are independently a bond or (CH2)mCH(R7)(CH2)n; m=0-1, n=0-2; R is hydrogen or halogen; R 1 and R 2 are independently selected from hydrogen halogen, CF 3 , CN, OR 8 , NR 9 R 10 , NR 9 COR 11 , NR 9 SO 2 R 11 or C 1-6 alkyl optionally substituted by hydroxyl, C 1-6 alkoxy or NR 9 R 10 ; R 3 is hydrogen, halogen, CF 3 , CN, OR 8 , SR 8 or SO 2 R 11 ; R 4 is hydrogen, halogen, CF 3 , OR 9 , NR 9 R 10 , NR 9 COR 11 , NR 9 SO 2 R 11 or C 1-6 alkyl optionally substituted by hydroxyl, C 1-6 alkoxy or NR 9 R 10 ; R 5 is hydrogen or C 1-6 alkyl optionally substituted by hydroxyl, C 1-6 alkoxy or NR 9 R 10 ; R6 is hydrogen, fluorine, C1-6 alkyl, or C1-6 alkoxy; R 6 is hydrogen, fluorine, C 1-6 alkyl, or C 1-6 alkoxy; R 7 is hydrogen, C 1-6 alkyl, phenyl or C 1-3 alkylphenyl wherein said phenyl groups are optionally substituted by one or more substituents selected from halogen, C 1-6 alkyl, CF 3 , OCF 3 or OR 9 ; R 8 is hydrogen or C 1-6 alkyl optionally substituted by fluorine, C 1-6 alkoxy or NR 9 R 10 , R 9 is hydrogen, C 1-6 alkyl or C 1-3 alkylphenyl wherein said phenyl group is optionally substituted by one or more substituents selected from halogen, C 1-6 alkyl, CF 3 , OR 8 , NR 9 R 10 Or OCF 3 ; R 10 is hydrogen, C 1-6 alkyl, C 1-6 alkenyl, phenyl or C 1-3 alkylphenyl wherein said phenyl groups are optionally substituted by one or more substituents selected from halogen, C 1-6 alkyl, CF 3 , OR 8 or OCF 3 ; or the groups R 9 and R 10 when they are attached to a nitrogen atom may together form a 5- or 6-membered ring which optionally contains one further heteroatom selected from NR 9 , S and O; and R 11 is C 1-6 alkyl or a phenyl group optionally substituted by one or more substituents selected from halogen, C 1-6 alkyl, CF 3 , OCF 3 or OR 8 is provided. The compounds are useful in treating amyloid related diseases.

  该化合物的结构式（I）或其药用可接受的盐或前药：其中X和Y分别独立为NR5或O；W和Z分别独立为键或（CH2）mCH(R7)(CH2)n；m=0-1，n=0-2；R为氢或卤素；R1和R2分别选自氢卤素，CF3，CN，OR8，NR9R10，NR9COR11，NR9SO2R11或C1-6烷基，可选择地被羟基，C1-6烷氧基或NR9R10取代；R3为氢，卤素，CF3，CN，OR8，SR8或SO2R11；R4为氢，卤素，CF3，OR9，NR9R10，NR9COR11，NR9SO2R11或C1-6烷基，可选择地被羟基，C1-6烷氧基或NR9R10取代；R5为氢或C1-6烷基，可选择地被羟基，C1-6烷氧基或NR9R10取代；R6为氢，氟，C1-6烷基或C1-6烷氧基；R7为氢，C1-6烷基，苯基或C1-3烷基苯基，其中所述苯基可选择地被一个或多个取代基取代，所述取代基选自卤素，C1-6烷基，CF3，OCF3或OR9；R8为氢或C1-6烷基，可选择地被氟，C1-6烷氧基或NR9R10取代；R9为氢，C1-6烷基或C1-3烷基苯基，其中所述苯基可选择地被一个或多个取代基取代，所述取代基选自卤素，C1-6烷基，CF3，OR8，NR9R10或OCF3；R10为氢，C1-6烷基，C1-6烯基，苯基或C1-3烷基苯基，其中所述苯基可选择地被一个或多个取代基取代，所述取代基选自卤素，C1-6烷基，CF3，OR8或OCF3；或当连接到氮原子时，R9和R10组合可形成一个可选择地含有来自NR9，S和O的进一步杂原子的5-或6-成员环；R11为C1-6烷基或一个苯基，可选择地被一个或多个取代基取代，所述取代基选自卤素，C1-6烷基，CF3，OCF3或OR8。这些化合物在治疗与淀粉样蛋白相关的疾病中很有用。
• Highly Functionalized Biaryls via Suzuki-Miyaura Cross-Coupling Catalyzed by Pd@MOF under Batch and Continuous Flow Regimes
  作者：Vlad Pascanu、Peter R. Hansen、Antonio Bermejo Gómez、Carles Ayats、Ana E. Platero-Prats、Magnus J. Johansson、Miquel À. Pericàs、Belén Martín-Matute

  DOI：10.1002/cssc.201402858

  日期：2015.1

  currently existing commercial procedures. Most importantly, Pd@MIL‐101‐NH2 was packed in a micro‐flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chemistry for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large‐scale

  通过在功能化介孔MOF（8 wt％Pd @ MIL-101（Cr）-NH 2）中负载的Pd纳米粒子催化的Suzuki-Miyaura交叉偶联反应，成功合成了多种多样的40多种高度官能化的联芳基。尽管存在各种官能团和/或几个杂原子，但可以在迄今报道的某些最温和的条件下实现这一目标，并且可以保持对金属物种浸出的强有力控制。一些目标分子是药物合成中的重要中间体，我们清楚地举例说明了该催化系统的多功能性，与当前现有的商业程序相比，该催化系统的收率更高。最重要的是，Pd @ MIL-101-NH 2将其装在微流反应器中，这代表了在流化学中用于催化应用的MOF上负载的金属纳米颗粒的首次报道。在不替换催化剂的情况下，通过连续实验创建了一个11个分离的化合物的小型文库，证明了该催化剂在大规模应用中的潜力。
• [EN] HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES HÉTÉROCYCLIQUES DU RÉCEPTEUR DU CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2015161014A1

  公开（公告）日：2015-10-22

  The present invention is directed to heterocyclic compounds which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及杂环化合物，其是CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1
  作者：Lewis Gazzard、Karen Williams、Huifen Chen、Lorraine Axford、Elizabeth Blackwood、Brenda Burton、Kerry Chapman、Peter Crackett、Joy Drobnick、Charles Ellwood、Jennifer Epler、Michael Flagella、Emanuela Gancia、Matthew Gill、Simon Goodacre、Jason Halladay、Joanne Hewitt、Hazel Hunt、Samuel Kintz、Joseph Lyssikatos、Calum Macleod、Sarah Major、Guillaume Médard、Raman Narukulla、Judi Ramiscal、Stephen Schmidt、Eileen Seward、Christian Wiesmann、Ping Wu、Sharon Yee、Ivana Yen、Shiva Malek

  DOI：10.1021/acs.jmedchem.5b00464

  日期：2015.6.25

  Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analogue synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：SENEXIS LTD

  公开号：WO2011144578A1

  公开（公告）日：2011-11-24

  A compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof wherein X is N or CH; Q is NR6 or O; A1 and A2 are independently hydrogen or C1-6 alkyl or may together form a carbonyl group; R1 and R2 are independently hydrogen, halogen, CF3, CN, OR7, OR8, NR8R9, NR8COR10, NR8S02R10, S02NR8R9, SO2R10 or C1-6 alkyl optionally and independently substituted by one or more of hydroxyl, C1-6 alkoxy, halogen or NR8 R9; R 3 is hydrogen, halogen, CF3 or OR 7; R4 is hydrogen, halogen, CF3, OR8, NR8R9, NR8COR10, NR8S02R10 or C1-6 alkyl optionally substituted by hydroxyl, C1-6 alkoxy or NR 8 R 9; or when R3 and R4 are positioned ortho and taken together form -0(CH2)mO-, where m is 1-3; R5 is hydrogen or C1-6 alkyl optionally substituted by hydroxyl, C1-6 alkoxy or NR8 R9; R6 is hydrogen or C1-6 alkyl; R7 is hydrogen or C1-6 alkyl optionally substituted by OR8 or NR8R9; R8 is hydrogen, C1-6 alkyl, optionally substituted by hydroxyl or C1-6 alkoxy or C1-3 alkylphenyl wherein said phenyl group is optionally substituted by one or more substituents selected from halogen, C1-6 alkyl, CF3, OR7, NR8R9 or OCF3; or the groups R8 and R9 when they are attached to a nitrogen atom may together form a 5- or 6-membered ring which optionally contains one further heteroatom selected from NR7, S and O said 5 or 6 membered ring being optionally substituted by hydroxyl or C1-6 alkoxy; or the groups R8 and R9 when they are attached to a nitrogen atom may together form an azetidinyl ring optionally substituted by hydroxyl or C1-6 alkoxy; and R10 is C1-6 alkyl or a phenyl group optionally substituted by one or more substituents selected from halogen, C1-6 alkyl, CF3, OCF3 or OR7; and n is 1 or 2. The use of the compounds in treating amyloid disease is also disclosed.

  式（I）的化合物或其药学上可接受的盐或前药，其中X为N或CH；Q为NR6或O；A1和A2独立地为氢或C1-6烷基，或者可共同形成一个羰基团；R1和R2独立地为氢、卤素、CF3、CN、OR7、OR8、NR8R9、NR8COR10、NR8S02R10、S02NR8R9、SO2R10或C1-6烷基，可选地并独立地被一个或多个羟基、C1-6烷氧基、卤素或NR8R9取代；R3为氢、卤素、CF3或OR7；R4为氢、卤素、CF3、OR8、NR8R9、NR8COR10、NR8S02R10或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；或者当R3和R4位于邻位并共同形成-0(CH2)mO-时，其中m为1-3；R5为氢或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；R6为氢或C1-6烷基；R7为氢或C1-6烷基，可选地被OR8或NR8R9取代；R8为氢、C1-6烷基，可选地被羟基或C1-6烷氧基或C1-3烷基苯基取代，其中所述苯基可选地被一个或多个卤素、C1-6烷基、CF3、OR7、NR8R9或OCF3中的一种或多种取代基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个含有一个进一步异原子（选自NR7、S和O）的5-或6-成员环，所述5-或6-成员环可选地被羟基或C1-6烷氧基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个可选地被羟基或C1-6烷氧基取代的氮杂环戊烷环；R10为C1-6烷基或一个苯基，可选地被一个或多个卤素、C1-6烷基、CF3、OCF3或OR7中的一种或多种取代基取代；n为1或2。还公开了这些化合物在治疗淀粉样蛋白病中的用途。