2-[4-(溴甲基)苯基]-5-氟吡啶 | 1257426-56-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-[4-(溴甲基)苯基]-5-氟吡啶
• 英文名称: 2-(4-(bromomethyl)phenyl)-5-fluoropyridine
• 英文别名: 2-[4-(bromomethyl)phenyl]-5-fluoropyridine
• CAS: 1257426-56-4
• 化学式: C₁₂H₉BrFN
• 分子量: 266.113
• InChiKey: OYAHFICQIKUCAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[4-(溴甲基)苯基]-5-氟吡啶 、 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazole-2-thiol 在 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 以66%的产率得到2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(4-(5-fluoropyridin-2-yl)benzylthio)-1,3,4-oxadiazole
  参考文献：
  名称：

  Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia

  摘要：

  The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML) may require alpha-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3 alpha selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3 alpha/beta with the highest GSK-3 alpha selectivity reported to dtae. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3 alpha targeting in AML cell lines was achieved with compound 27, resulting in a strong differrentiation phenotype and colony formation impairment, confirming the potential of GSK-3 alpha inhibition in AML therapy.

  DOI：

  10.1021/acs.jmedchem.5b01200
• 作为产物：
  描述：

  2-溴-5-氟吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride N-溴代丁二酰亚胺(NBS) 、 sodium carbonate 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.33h， 生成 2-[4-(溴甲基)苯基]-5-氟吡啶
  参考文献：
  名称：

  NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY

  摘要：

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗联合使用。

  公开号：

  US20120028973A1

文献信息

• [EN] NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY<br/>[FR] NITROIMIDAZOOXAZINES ET LEURS UTILISATIONS EN THÉRAPIE ANTITUBERCULEUSE
  申请人：GLOBAL ALLIANCE FOR TB DRUG DEV

  公开号：WO2011014774A1

  公开（公告）日：2011-02-03

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗方法结合使用。
• NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY
  申请人：Denny William Alexander

  公开号：US20120028973A1

  公开（公告）日：2012-02-02

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法，以及它们作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗联合使用。
• Discovery of Potent and Selective Inhibitors of Phosphodiesterase 1 for the Treatment of Cognitive Impairment Associated with Neurodegenerative and Neuropsychiatric Diseases
  作者：Peng Li、Hailin Zheng、Jun Zhao、Lei Zhang、Wei Yao、Hongwen Zhu、J. David Beard、Koh Ida、Weston Lane、Gyorgy Snell、Satoshi Sogabe、Charles J. Heyser、Gretchen L. Snyder、Joseph P. Hendrick、Kimberly E. Vanover、Robert E. Davis、Lawrence P. Wennogle

  DOI：10.1021/acs.jmedchem.5b01751

  日期：2016.2.11

  excellent selectivity against all other PDE families and showed good efficacy in vivo. Currently, this investigational new drug is in Phase I clinical development and being considered for the treatment of several indications including cognitive deficits associated with schizophrenia and Alzheimer’s disease, movement disorders, attention deficit and hyperactivity disorders, and other central nervous system (CNS)

  设计并合成了多种多样的3-氨基吡唑并[3,4- d ]嘧啶酮。研究了这些多环化合物作为磷酸二酯酶1（PDE1）抑制剂的结构-活性关系及其理化和药代动力学特性。该新型支架的系统优化最终确定了临床候选药物（（6a R，9a S）-2-（4-（6-氟吡啶-2--2-基）苄基）-5-甲基-3-（苯基氨基）- 5,6a，7,8,9,9a-六氢环戊[4,5]咪唑并[1,2- a ]吡唑并[4,3 - e ]嘧啶-4-（2 H）一磷酸（ITI-214）对PDE1表现出皮摩尔抑制能力，对所有其他PDE家族表现出优异的选择性，并在体内具有良好的疗效。目前，该研究用新药正处于I期临床开发阶段，正在考虑用于治疗多种适应症，包括与精神分裂症和阿尔茨海默氏病相关的认知缺陷，运动障碍，注意力缺陷和多动障碍以及其他中枢神经系统（CNS）和非-CNS疾病。
• Nitroimidazooxazines and their uses in anti-tubercular therapy
  申请人：Denny William Alexander

  公开号：US09198913B2

  公开（公告）日：2015-12-01

  The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型硝基咪唑噁啉类化合物，其制备方法以及其作为治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗联合使用。
• Synthesis and Structure−Activity Relationships of Aza- and Diazabiphenyl Analogues of the Antitubercular Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Iveta Kmentova、Hamish S. Sutherland、Brian D. Palmer、Adrian Blaser、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny、Andrew M. Thompson

  DOI：10.1021/jm101288t

  日期：2010.12.9

  New heterocyclic analogues of the potent biphenyl class derived from antitubercular drug PA-824 were prepared, aiming to improve aqueous solubility but maintain high metabolic stability and efficacy. The strategy involved replacement of one or both phenyl groups by pyridine, pyridazine, pyrazine, or pyrimidine, in order to reduce lipophilicity. For para-linked biaryls, hydrophilicities (ClogP) correlated with measured solubilities, but highly soluble bipyridine analogues displayed weak antitubercular activities. A terminal pyridine or proximal heterocycle allowed retention of potency and provided solubility improvements, particularly at low pH, with examples from the latter classes displaying the better in vivo efficacies, high metabolic stabilities, and excellent pharmacokinetics. Five such compounds were >100-fold better than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection, and two orally bioavailable pyridine analogues (3-4-fold more soluble than the parent at low pH) were superior to antitubercular drug OPC-67683 in a chronic infection model.