4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one | 1094435-32-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
• 英文别名: 4-(3-bromopropyl)-4H-benzo[1,4]oxazin-3-one；4-(3-bromo-propyl)-4H-benzo[1,4]oxazin-3-one；4-(3-bromopropyl)-1,4-benzoxazin-3-one
• CAS: 1094435-32-1
• 化学式: C₁₁H₁₂BrNO₂
• 分子量: 270.126
• InChiKey: JTFSZCMGBCWJMG-UHFFFAOYSA-N

物化性质

• 沸点：
  448.0±45.0 °C(Predicted)
• 密度：
  1.483±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one 在 sodium azide 、 四丁基溴化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以75%的产率得到4-(3-azidopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
  参考文献：
  名称：

  Rational design, synthesis and anti-proliferative evaluation of novel 1,4-benzoxazine-[1,2,3]triazole hybrids

  摘要：

  A series of novel 1,2,3-triazole-1,4-benzoxazine hybrids 5a-n were efficiently synthesized employing click chemistry approach and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 5n and 5g exhibited promising anti-proliferative activity with GI(50) values ranging from 1.2 to 2.5 mu M and 0.1-1.1 mu M respectively against all cell lines, like HeLa, MDA-MB-231, MIAPACA and IMR32, while compound 51 showed significant activity against MDA-MB-231 and IMR32 with GI(50) values ranging from 1.1 and 1.4 mu M. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,2,3-triazole-1,4-benzoxazine hybrids. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.051
• 作为产物：
  描述：

  2-氨基苯酚 在 苄基三乙基氯化铵 、 碳酸氢钠 、 potassium carbonate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
  参考文献：
  名称：

  (E)-2-亚苄基-N-(3-(3-氧代-2,3-二氢-4H苯并[b][1,4]恶嗪-4-基)丙基)肼-1-硫代硫酰胺的合成

  摘要：

  一系列新型取代-(E)-2-亚苄基-N-(3-(3-氧代-2,3-二氢-4H-苯并[b][1,4]恶嗪-4-基)丙基)肼通过 (Z)-N'-亚苄基肼硫代碳酰胺 (8a-j) 与 4-(3-溴-丙基)-2H-苯并[b] 反应，合成了 -1-硫代碳酰胺 (9a-j)，收率令人满意。 [1,4]恶嗪-3(4H)-酮(5)在K2CO3和干燥N,N-二甲基甲酰胺中。使用 1H NMR、IR 和质谱方法确认了新型硫代碳酰胺 (9a-j) 的结构

  DOI：

  10.14233/ajchem.2023.27601

文献信息

• [EN] NOVEL HETEROCYCLIC CARBOXAMIDES AS M1 AGONISTS<br/>[FR] NOUVEAUX CARBOXAMIDES HÉTÉROCYCLIQUES COMME AGONISTES DE M1
  申请人：LUNDBECK & CO AS H

  公开号：WO2009106534A1

  公开（公告）日：2009-09-03

  The present invention relates to novel M1 agonistic compounds of formula (I) and their use in the treatment of cognitive impairment associated i.a. with schizophrenia and in the treatment of other diseases mediated by the muscarinic M1 receptor.

  本发明涉及式(I)的新型M1激动化合物及其在治疗与精神分裂症等疾病相关的认知障碍以及在治疗其他通过胆碱能M1受体介导的疾病中的应用。
• Discovery of <i>N</i>-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): An Allosteric Muscarinic M₁ Receptor Agonist with Unprecedented Selectivity and Procognitive Potential
  作者：Anette G. Sams、Morten Hentzer、Gitte K. Mikkelsen、Krestian Larsen、Christoffer Bundgaard、Niels Plath、Claus T. Christoffersen、Benny Bang-Andersen

  DOI：10.1021/jm100697g

  日期：2010.9.9

  The discovery and structure activity relationship (SAR) of a series of allosteric muscarinic M, receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M-1 receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.
• Hit-to-lead investigation of a series of novel combined dopamine D2 and muscarinic M1 receptor ligands with putative antipsychotic and pro-cognitive potential
  作者：Anette Graven Sams、Krestian Larsen、Gitte Kobberøe Mikkelsen、Morten Hentzer、Claus Tornby Christoffersen、Klaus Gjervig Jensen、Kristen Frederiksen、Benny Bang-Andersen

  DOI：10.1016/j.bmcl.2012.05.048

  日期：2012.8

  We describe the discovery of a series of compounds based on 1-3-[4-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-3,4-dihydro-1H-quinolin-2-one (3), showing combined D-2 receptor affinity and M-1 receptor agonism. Based on a strategy of controlling log P, we herein describe a hit-to-lead investigation with the aim of retaining the combined D-2/M-1 profile, while removing the propensity of the compounds to inhibit the hERG channel, as well as at obtaining acceptable pharmacokinetic properties. Although a SAR was evident for all four parameters in question, it was not possible to separate hERG channel inhibition and D-2 receptor affinity by this effort; whilst it was feasible to obtain compounds with M-1 receptor agonism, acceptable clearance, and weak hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.
• Proof of Concept Study for Designed Multiple Ligands Targeting the Dopamine D₂, Serotonin 5-HT_2A, and Muscarinic M₁ Acetylcholine Receptors
  作者：Monika Szabo、Herman D. Lim、Carmen Klein Herenbrink、Arthur Christopoulos、J. Robert Lane、Ben Capuano

  DOI：10.1021/jm5013243

  日期：2015.2.12

  Herein we describe the hybridization of a benzoxazinone M-1 scaffold with D-2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M-1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D-2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M-1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.
• Rational design, synthesis and anti-proliferative evaluation of novel 1,4-benzoxazine-[1,2,3]triazole hybrids
  作者：Rajitha Bollu、Jyothsna Devi Palem、Rajashaker Bantu、Vijayacharan Guguloth、Lingaiah Nagarapu、Sowjanya Polepalli、Nishant Jain

  DOI：10.1016/j.ejmech.2014.10.051

  日期：2015.1

  A series of novel 1,2,3-triazole-1,4-benzoxazine hybrids 5a-n were efficiently synthesized employing click chemistry approach and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 5n and 5g exhibited promising anti-proliferative activity with GI(50) values ranging from 1.2 to 2.5 mu M and 0.1-1.1 mu M respectively against all cell lines, like HeLa, MDA-MB-231, MIAPACA and IMR32, while compound 51 showed significant activity against MDA-MB-231 and IMR32 with GI(50) values ranging from 1.1 and 1.4 mu M. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,2,3-triazole-1,4-benzoxazine hybrids. (C) 2014 Elsevier Masson SAS. All rights reserved.