1-(10H-phenothiazin-10-yl)-2-phenylethanone | 54012-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 1-(10H-phenothiazin-10-yl)-2-phenylethanone
• 英文别名: 10-phenylacetyl-10H-phenothiazine；10-phenylacetyl-phenothiazine；10-Phenylacetyl-phenothiazin；1-(10H-Phenothiazin-10-yl)-2-phenylethan-1-one；1-phenothiazin-10-yl-2-phenylethanone
• CAS: 54012-72-5
• 化学式: C₂₀H₁₅NOS
• 分子量: 317.411
• InChiKey: ODRJXAKDUXFICI-UHFFFAOYSA-N

物化性质

• 沸点：
  562.1±30.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(10H-phenothiazin-10-yl)-2-phenylethanone 在 双氧水 、 溶剂黄146 作用下， 生成 10-phenylacetyl-phenothiazine-5,5-dioxide
  参考文献：
  名称：

  Oxidation of 10-Acyl- and 10-Alkylphenothiazines

  摘要：

  DOI：

  10.1021/ja01117a509
• 作为产物：
  描述：

  吩噻嗪 、 苯乙酰氯 以 甲苯 为溶剂， 以94%的产率得到1-(10H-phenothiazin-10-yl)-2-phenylethanone
  参考文献：
  名称：

  三环吩噻嗪和吩硒嗪衍生物可作为治疗阿尔茨海默氏病的潜在多靶点药物

  摘要：

  设计，合成和评估了一组三环吩噻嗪（6a，6b和7a-1）和吩硒嗪（12a，12b和13a-1），作为针对阿尔茨海默氏病的胆碱能，淀粉样蛋白和氧化应激途径的多目标配体。吩噻嗪衍生物7j（2-氯-10 H-吩噻嗪-10-基-（4-甲氧基苯基）甲酮）被确定为最佳的双重非选择性胆碱酯酶抑制剂（AChE IC 50 = 5.9±0.6μM; BuChE IC 50 = 5.3±0.5μM），而在相应的吩硒嗪系列中，13j（2-氯-10 H-phenoselenazin-10-yl-（（4-methoxyphenyl）methanone）表现出良好的非选择性胆碱酯酶抑制作用（AChE IC 50 = 5.8±0.4μM; BuChE IC 50 = 4.9±0.5μM）。有趣的是，N-10未取代的吩噻嗪6a（AChE IC 50 = 7.3±0.6μM； BuChE IC 50 = 5.8±0.5μM；Aβ1–42聚集抑制率=

  DOI：

  10.1039/c5md00274e

文献信息

• Selective reversible inhibition of human butyrylcholinesterase by aryl amide derivatives of phenothiazine
  作者：Sultan Darvesh、Robert S. McDonald、Katherine V. Darvesh、Diane Mataija、Sarah Conrad、Geraldine Gomez、Ryan Walsh、Earl Martin

  DOI：10.1016/j.bmc.2007.06.060

  日期：2007.10

  Evidence suggests that specific inhibition of butyrylcholinesterase may be an appropriate focus for the development of more effective drugs to treat dementias such as Alzheimer's disease. Butyrylcholinesterase is a co-regulator of cholinergic neuro-transmission and its activity is increased in Alzheimer's disease, and is associated with all neuropathological lesions in this disease. Some selective butyrylcholinesterase inhibitors have already been reported to increase acetylcholine levels and to reduce the formation of abnormal amyloid found in Alzheimer's disease. Synthesized N-(10)-aryl and N-(10)-alkylaryl amides of phenothiazine are specific inhibitors of butyrylcholinesterase. In some cases, inhibition constants in the nanomolar range are achieved. Enzyme specificity and inhibitor potency of these molecules can be related to molecular volumes, steric and electronic factors. Computed logP values indicate high potential for these compounds to cross the blood-brain barrier. Use of such butyrylcholinesterase inhibitors could provide direct evidence for the importance of this enzyme in the normal nervous system and in Alzheimer's disease. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis of New 10-Substituted Phenothiazine Derivatives
  作者：M. M. El-Kerdawy、H. A. Moharram、M. N. Tolba

  DOI：10.1002/prac.19743160322

  日期：——
• [EN] NOVEL N-SUBSTITUTED PHENOTHIAZINES AND THEIR USE AS MODULATORS OF SERINE HYDROLASE ENZYMES<br/>[FR] NOUVELLES PHENOTHIAZINES N-SUBSTITUEES ET LEUR UTILISATION EN TANT QUE MODULATEUR D'ENZYME HYDROLASES A SERINE
  申请人：UNIV DALHOUSIE

  公开号：WO2001092240A1

  公开（公告）日：2001-12-06

  The present invention is directed to phenothiazine compounds of formula (I), wherein R is: (a) a branched or straight chain (C1-C6)alkyl group unsubstituted or substituted by phenyl, halo or -NR1R2, wherein R1 and R2 are independently H, a branched or straight chain (C1-C6)alkyl group or R1 and R2 together with the nitrogen atom to which they are bonded form a 5- or 6-membered ring; (b) phenyl; or (c) -NR3R4, wherein R3 and R4 are independently; (i) H, (ii) a branched or straight chain (C1-C6)alkyl group unsubstituted or substituted by (C1-C4)alkoxy, phenyl or -NR5R6, wherein R5 and R6 are independently H, a branched or straight chain (C1-C¿4)alkyl group, phenothiazine carbonyl or R5 and R6 taken together with the nitrogen atom to which they are bonded form a 5- or 6-membered ring; (v) a (C5-C6)cycloalkyl group; or (iv) R3 and R4 together with the nitrogen atom to which they are bonded form pyrrolidino, piperidino, morpholino, piperazino or 4-methylpiperazino, or a pharmacologically acceptable salt thereof, for use in the treatment of Alzheimer's disease and other conditions. Compounds of formula (I) modulate the activity of serine hydrolase enzymes, for example, they are cholinesterase inhibitors.
• Oxidation of 10-Acyl- and 10-Alkylphenothiazines
  作者：Henry Gilman、R. David Nelson

  DOI：10.1021/ja01117a509

  日期：1953.11
• Tricyclic phenothiazine and phenoselenazine derivatives as potential multi-targeting agents to treat Alzheimer's disease
  作者：Gary Tin、Tarek Mohamed、Nyasha Gondora、Michael A. Beazely、Praveen P. N. Rao

  DOI：10.1039/c5md00274e

  日期：——

  A group of tricyclic phenothiazines (6a, 6b and 7a–l) and phenoselenazines (12a, 12b and 13a–l) was designed, synthesized and evaluated as multi-targeting ligands aimed at the cholinergic, amyloid and oxidative stress pathways of Alzheimer's disease. The phenothiazine derivative 7j (2-chloro-10H-phenothiazin-10-yl-(4-methoxyphenyl)methanone) was identified as the best dual, non-selective cholinesterase

  设计，合成和评估了一组三环吩噻嗪（6a，6b和7a-1）和吩硒嗪（12a，12b和13a-1），作为针对阿尔茨海默氏病的胆碱能，淀粉样蛋白和氧化应激途径的多目标配体。吩噻嗪衍生物7j（2-氯-10 H-吩噻嗪-10-基-（4-甲氧基苯基）甲酮）被确定为最佳的双重非选择性胆碱酯酶抑制剂（AChE IC 50 = 5.9±0.6μM; BuChE IC 50 = 5.3±0.5μM），而在相应的吩硒嗪系列中，13j（2-氯-10 H-phenoselenazin-10-yl-（（4-methoxyphenyl）methanone）表现出良好的非选择性胆碱酯酶抑制作用（AChE IC 50 = 5.8±0.4μM; BuChE IC 50 = 4.9±0.5μM）。有趣的是，N-10未取代的吩噻嗪6a（AChE IC 50 = 7.3±0.6μM； BuChE IC 50 = 5.8±0.5μM；Aβ1–42聚集抑制率=