N-(5-bromo-2-chloro-pyridine-3-yl)cyclopropyl-sulfonamide | 1086065-58-8

• 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
• 英文名称: N-(5-bromo-2-chloro-pyridine-3-yl)cyclopropyl-sulfonamide
• 英文别名: N-(5-bromo-2-chloro-3-pyridinyl)cyclopropanesulfonamide；N-(5-bromo-2-chloropyridin-3-yl)cyclopropanesulfonamide
• CAS: 1086065-58-8
• 化学式: C₈H₈BrClN₂O₂S
• 分子量: 311.587
• InChiKey: GLMLMHRBDFXBER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(5-bromo-2-chloro-pyridine-3-yl)cyclopropyl-sulfonamide 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 生成 N-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)pyridin-2-ylamino)-2-chloropyridin-3-YL)cyclopropanesulfonamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffold

  摘要：

  Phosphoinositide 3-kinase (PI3K) is an important target in oncology due to the deregulation of the PI3K/Akt signaling pathway in a wide variety of tumors. A series of 4-amino-6-methyl-1,3,5-triazine sulfonamides were synthesized and evaluated as inhibitors of PI3K. The synthesis, in vitro biological activities, pharmacokinetic and in vivo pharmacodynamic profiling of these compounds are described. The most promising compound from this investigation (compound 3j) was found to be a pan class I PI3K inhibitor with a moderate (>10-fold) selectivity over the mammalian target of rapamycin (mTOR) in the enzyme assay. In a U87 MG cellular assay measuring phosphorylation of Akt, compound 3j displayed low double digit nanomolar IC50 and exhibited good oral bioavailability in rats (F-oral = 63%). Compound 3j also showed a dose dependent reduction in the phosphorylation of Akt in a U87 tumor pharmacodynamic model with a plasma EC50 = 193 nM (91 ng/mL). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.078
• 作为产物：
  描述：

  2-氯-3-氨基-5-溴吡啶 、 环丙磺酰氯 在 lithium hexamethyldisilazane 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以33%的产率得到N-(5-bromo-2-chloro-pyridine-3-yl)cyclopropyl-sulfonamide
  参考文献：
  名称：

  吗啉并喹啉类化合物，其制备方法和用途

  摘要：

  本发明公开的吗啉并喹啉类化合物，为具有以下通式（I）的化合物：其中，R1选自C1-C6烷基，芳基，胺基，C3-C10环烷基，杂环基，杂芳基；R2选自氢，卤素，-OR10；R3选自氢，-NHR10，-NHC(=O)R10；R4选自氢，C1-C6烷基，-C(=O)R10，-S(=O)2R10；R5，R6选自氢，C1-C6烷基，卤素；R7，R8选自氢，C1-C6烷基，卤素，或R7，R8合并为=O；R9选自氢，C1-C6烷基，-OR10，卤素；其中R10为氢，C1-C6烷基，C3-C10环烷基，芳基，杂芳基；并且，R1～10中所述的烷基、烷氧基、芳基、杂芳基均可被一个或多个基团任选地取代，这些基团包括烷基、烯基、炔基、卤素、烷氧基、芳基、杂芳基、氨基、胺基、氰基、硝基、羧基、酯基、胺甲酰基、磺酰基、磺酰胺基等。本发明公开的吗啉并喹啉类化合物作为药物用以治疗与PI3K/mTOR相关的疾病。

  公开号：

  CN103936762B

文献信息

• 吗啉并喹啉类化合物，其制备方法和用途
  申请人：上海汇伦生命科技有限公司

  公开号：CN103936762B

  公开（公告）日：2016-02-24

  本发明公开的吗啉并喹啉类化合物，为具有以下通式（I）的化合物：其中，R1选自C1-C6烷基，芳基，胺基，C3-C10环烷基，杂环基，杂芳基；R2选自氢，卤素，-OR10；R3选自氢，-NHR10，-NHC(=O)R10；R4选自氢，C1-C6烷基，-C(=O)R10，-S(=O)2R10；R5，R6选自氢，C1-C6烷基，卤素；R7，R8选自氢，C1-C6烷基，卤素，或R7，R8合并为=O；R9选自氢，C1-C6烷基，-OR10，卤素；其中R10为氢，C1-C6烷基，C3-C10环烷基，芳基，杂芳基；并且，R1～10中所述的烷基、烷氧基、芳基、杂芳基均可被一个或多个基团任选地取代，这些基团包括烷基、烯基、炔基、卤素、烷氧基、芳基、杂芳基、氨基、胺基、氰基、硝基、羧基、酯基、胺甲酰基、磺酰基、磺酰胺基等。本发明公开的吗啉并喹啉类化合物作为药物用以治疗与PI3K/mTOR相关的疾病。
• QUINAZOLINE DERIVATIVES AS P13 KINASE INHIBITORS
  申请人：ADAMS Nicholas D.

  公开号：US20090018131A1

  公开（公告）日：2009-01-15

  Invented is a method of inhibiting the activity/function of PI3 kinases using quinazoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinazoline derivatives.

  本发明涉及使用喹唑啉衍生物来抑制PI3激酶的活性/功能的方法。本发明还涉及使用喹唑啉衍生物治疗以下一种或多种疾病状态的方法：自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺部损伤。通过给予喹唑啉衍生物进行治疗。
• QUINAZOLINE DERIVATIVES AS PI3 KINASE INHIBITORS
  申请人：GlaxoSmithKline LLC

  公开号：EP2167092A2

  公开（公告）日：2010-03-31
• [EN] QUINAZOLINE DERIVATIVES AS PI3 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE QUINAZOLINE EN TANT QU'INHIBITEURS DE LA KINASE PI3
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2008157191A2

  公开（公告）日：2008-12-24

  [EN] Invented is a method of inhibiting the activity/function of P13 kinases using quinazoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinazoline derivatives.
  [FR] L'invention concerne un procédé d'inhibition de l'activité/la fonction des kinases P13 utilisant des dérivés de quinazoline. Un procédé de traitement d'un ou plusieurs états maladifs sélectionnés à partir de : troubles auto-immuns, maladies inflammatoires, maladies cardiovasculaires, maladies neurodégénératives, allergies, asthme, pancréatite, défaillance multivicérale, néphropathies, agrégation plaquettaire, cancer, mobilité du sperme, rejet de transplantation, rejet de greffe et lésions pulmonaires par l'administration de dérivés de quinazoline.
• Synthesis and structure–activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffold
  作者：Ryan P. Wurz、Longbin Liu、Kevin Yang、Nobuko Nishimura、Yunxin Bo、Liping H. Pettus、Sean Caenepeel、Daniel J. Freeman、John D. McCarter、Erin L. Mullady、Tisha San Miguel、Ling Wang、Nancy Zhang、Kristin L. Andrews、Douglas A. Whittington、Jian Jiang、Raju Subramanian、Paul E. Hughes、Mark H. Norman

  DOI：10.1016/j.bmcl.2012.06.078

  日期：2012.9

  Phosphoinositide 3-kinase (PI3K) is an important target in oncology due to the deregulation of the PI3K/Akt signaling pathway in a wide variety of tumors. A series of 4-amino-6-methyl-1,3,5-triazine sulfonamides were synthesized and evaluated as inhibitors of PI3K. The synthesis, in vitro biological activities, pharmacokinetic and in vivo pharmacodynamic profiling of these compounds are described. The most promising compound from this investigation (compound 3j) was found to be a pan class I PI3K inhibitor with a moderate (>10-fold) selectivity over the mammalian target of rapamycin (mTOR) in the enzyme assay. In a U87 MG cellular assay measuring phosphorylation of Akt, compound 3j displayed low double digit nanomolar IC50 and exhibited good oral bioavailability in rats (F-oral = 63%). Compound 3j also showed a dose dependent reduction in the phosphorylation of Akt in a U87 tumor pharmacodynamic model with a plasma EC50 = 193 nM (91 ng/mL). (C) 2012 Elsevier Ltd. All rights reserved.