1-[(5-甲基-1,2-恶唑-3-基)甲基]哌嗪 | 173850-51-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-[(5-甲基-1,2-恶唑-3-基)甲基]哌嗪
• 中文别名: 5(2H)-异噻唑酮,2-[(4-苯甲酰-1-哌啶基)羰基]-3-甲基-4-(1-甲基乙基)-
• 英文名称: 5-methyl-3-(N-piperazinomethyl) isoxazole
• 英文别名: 1-[(5-Methylisoxazol-3-yl)methyl]piperazine；5-methyl-3-(piperazin-1-ylmethyl)-1,2-oxazole
• CAS: 173850-51-6
• 化学式: C₉H₁₅N₃O
• mdl: MFCD06655908
• 分子量: 181.238
• InChiKey: PHLMNRYXLHHLJG-UHFFFAOYSA-N

物化性质

• 沸点：
  301.5±37.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  41.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氨基-5-溴-4-氯-3-硝基吡啶 、 1-[(5-甲基-1,2-恶唑-3-基)甲基]哌嗪 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 20.0h， 以0.17 g的产率得到5-bromo-4-[4-[(5-methyl-isoxazol-3-yl)methyl]piperazin-1-yl]-3-nitro-pyridin-2-ylamine
  参考文献：
  名称：

  Imidazo[4,5-b]pyridine Derivatives As Inhibitors of Aurora Kinases: Lead Optimization Studies toward the Identification of an Orally Bioavailable Preclinical Development Candidate

  摘要：

  Lead optimization studies using 7 as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors of Aurora kinases that possessed the 1-benzylpiperazinyl motif at the 7-position, and displayed favorable in vitro properties. Cocrystallization of Aurora-A with 40c (CCT137444) provided a clear understanding into the interactions of this novel class of inhibitors with the Aurora kinases. Subsequent physicochemical property refinement by the incorporation of solubilizing groups led to the identification of 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole (51, CCT137690) which is a potent inhibitor of Aurora kinases (Aurora-A IC(50) = 0.015 +/- 0.003 muM, Aurora-B IC(50) = 0.025 muM, Aurora-C IC(50) = 0.019 muM). Compound 51 is highly orally bioavailable, and in in vivo efficacy studies it inhibited the growth of SW620 colon carcinoma xenografts following oral administration with no observed toxicities as defined by body weight loss.

  DOI：

  10.1021/jm100262j
• 作为产物：
  描述：

  乙酰丙酮酸甲酯 在 dimethyl sulfide borane 、 硫酸 、 盐酸羟胺 、 sodium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 11.0h， 生成 1-[(5-甲基-1,2-恶唑-3-基)甲基]哌嗪
  参考文献：
  名称：

  Regioisomeric 3-, 4- and 5-aminomethyl isoxazoles: synthesis and muscarinic activity

  摘要：

  A series of 3-, 4- and 5-aminomethyl isoxazoles and isoxazoles with one or two additional methyl groups at the heterocycle were synthesized in order to investigate the structural requirements, ie heterocyclic moiety, regiochemistry and length of an aminoalkyl unit, for muscarinic activity. This was assayed on isolated rabbit vas deferens (M(1) receptor subtype) and isolated guinea-pig atrium (M(2) receptor subtype) and ileum (M(3) receptor subtype). The isoxazoles tested are one to three orders of magnitude less active than furane or oxadiazole derivatives, having similar structural characteristics except for the heterocycle. Thus, the differences in molecular point charges and charge distribution contribute to the muscarinic activity of these compounds more than small differences in molecular shape and conformational energies.

  DOI：

  10.1016/0223-5234(96)88303-6

文献信息

• Novel betulin derivatives, preparation thereof and use thereof
  申请人：Robinson N. Gary

  公开号：US20060205697A1

  公开（公告）日：2006-09-14

  The present invention relates to novel synthetic derivatives of betulin and the use of such derivatives as pharmaceuticals. The present invention is directed to novel compounds of Formula I: or a pharmaceutically acceptable salt or prodrug thereof.

  本发明涉及到白桦醇的新型合成衍生物及其作为药物的用途。本发明是针对式I的新型化合物而言：或其药物可接受的盐或前药。
• Pharmaceutical compounds
  申请人：Shuttleworth Stephen J.

  公开号：US20080207611A1

  公开（公告）日：2008-08-28

  Fused pyrimidines of formula (I): wherein R 1 -R 3 , A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof, have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  公式（I）的融合嘧啶： 其中R1-R3，A和n具有规范中描述的任何值；以及其药学上可接受的盐，具有作为PI3K抑制剂的活性，因此可用于治疗由与PI3激酶相关的异常细胞生长，功能或行为引起的疾病和障碍，如癌症，免疫障碍，心血管疾病，病毒感染，炎症，代谢/内分泌障碍和神经障碍。还描述了合成该化合物的过程。
• PHARMACEUTICAL COMPOUNDS
  申请人：Shuttleworth Stephen J.

  公开号：US20120258966A1

  公开（公告）日：2012-10-11

  Fused pyrimidines of formula (I): wherein R 1 -R 3 , A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof; have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.

  式（I）的融合嘧啶化合物：其中R1-R3，A和n具有规范中所述的任何值;以及其药学上可接受的盐;具有作为PI3K抑制剂的活性，因此可用于治疗由于PI3激酶引起的异常细胞生长，功能或行为而引起的疾病和障碍，例如癌症，免疫障碍，心血管疾病，病毒感染，炎症，代谢/内分泌障碍和神经障碍。还描述了合成化合物的过程。
• <i>N</i>-[6-(4-Butanoyl-5-methyl-1<i>H</i>-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1<i>H</i>-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist
  作者：Christophe Boldron、Angélina Besse、Marie-Françoise Bordes、Stéphanie Tissandié、Xavier Yvon、Benjamin Gau、Alain Badorc、Tristan Rousseaux、Guillaume Barré、Jérôme Meneyrol、Gernot Zech、Marc Nazare、Valérie Fossey、Anne-Marie Pflieger、Sandrine Bonnet-Lignon、Laurence Millet、Christophe Briot、Frédérique Dol、Jean-Pascal Hérault、Pierre Savi、Gilbert Lassalle、Nathalie Delesque、Jean-Marc Herbert、Françoise Bono

  DOI：10.1021/jm500588w

  日期：2014.9.11

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.
• US7750002B2
  申请人：——

  公开号：US7750002B2

  公开（公告）日：2010-07-06