N-butanoylphenothiazine | 52382-17-9

• 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: N-butanoylphenothiazine
• 英文别名: 10-butyryl-phenothiazine；10-Butyryl-phenothiazin；10H-Phenothiazine, 10-(1-oxobutyl)-；1-phenothiazin-10-ylbutan-1-one
• CAS: 52382-17-9
• 化学式: C₁₆H₁₅NOS
• 分子量: 269.367
• InChiKey: UYXTYYWMRACDJW-UHFFFAOYSA-N

物化性质

• 熔点：
  87.5-90.5 °C
• 沸点：
  484.0±15.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  N-butanoylphenothiazine 在 盐酸 、 三氯化铝 、 sodium hydride 作用下， 以 二硫化碳 、 乙醇 为溶剂， 反应 6.0h， 生成 1-[10-[3-(二甲基氨基)丙基]-10H-吩噻嗪-2-基]-1-丁酮
  参考文献：
  名称：

  锥虫嘧啶还原酶的吩噻嗪抑制剂可作为潜在的抗锥虫和抗疟药。

  摘要：

  鉴于锥虫硫磷在致病性锥虫和利什曼原虫的氧化还原防御中的作用，与谷胱甘肽作为哺乳动物宿主相比，锥虫硫磷还原酶的选择性抑制剂是对抗锥虫病和利什曼病的潜在药物。在本研究中，合理的药物设计方法被用于发现三环抗精神病药物分子框架，作为开发抑制剂的先导结构，对宿主的谷胱甘肽还原酶具有选择性的锥虫硫醇还原酶选择性。根据锥虫还原酶的同源模型结构，在研究的后期阶段，用Crisidia fasciculata的酶的X射线坐标代替，设计了一系列基于吩噻嗪的抑制剂。这些物质被证明是克氏锥虫中锥虫硫醇还原酶的可逆抑制剂，与锥虫硫磷作为底物线性竞争，与NADPH不竞争，这与乒乓球的bi bi动力学一致。合成以定义活性位点的结构-活性关系的类似物包括N-酰基吡嗪，2-取代的吩噻嗪和三取代的丙嗪。根据计算出的log P和摩尔折光率值对Ki和I50数据进行分析，提供了特别有利的小2-取代基（尤其是2-氯和2-三氟甲基）与酶

  DOI：

  10.1021/jm960814j
• 作为产物：
  描述：

  吩噻嗪 、 丁酰氯 以 甲苯 为溶剂， 反应 2.0h， 生成 N-butanoylphenothiazine
  参考文献：
  名称：

  锥虫嘧啶还原酶的吩噻嗪抑制剂可作为潜在的抗锥虫和抗疟药。

  摘要：

  鉴于锥虫硫磷在致病性锥虫和利什曼原虫的氧化还原防御中的作用，与谷胱甘肽作为哺乳动物宿主相比，锥虫硫磷还原酶的选择性抑制剂是对抗锥虫病和利什曼病的潜在药物。在本研究中，合理的药物设计方法被用于发现三环抗精神病药物分子框架，作为开发抑制剂的先导结构，对宿主的谷胱甘肽还原酶具有选择性的锥虫硫醇还原酶选择性。根据锥虫还原酶的同源模型结构，在研究的后期阶段，用Crisidia fasciculata的酶的X射线坐标代替，设计了一系列基于吩噻嗪的抑制剂。这些物质被证明是克氏锥虫中锥虫硫醇还原酶的可逆抑制剂，与锥虫硫磷作为底物线性竞争，与NADPH不竞争，这与乒乓球的bi bi动力学一致。合成以定义活性位点的结构-活性关系的类似物包括N-酰基吡嗪，2-取代的吩噻嗪和三取代的丙嗪。根据计算出的log P和摩尔折光率值对Ki和I50数据进行分析，提供了特别有利的小2-取代基（尤其是2-氯和2-三氟甲基）与酶

  DOI：

  10.1021/jm960814j

文献信息

• Structure–activity relationships for inhibition of human cholinesterases by alkyl amide phenothiazine derivatives
  作者：Sultan Darvesh、Robert S. McDonald、Andrea Penwell、Sarah Conrad、Katherine V. Darvesh、Diane Mataija、Geraldine Gomez、Angela Caines、Ryan Walsh、Earl Martin

  DOI：10.1016/j.bmc.2004.09.059

  日期：2005.1

  Several lines of evidence indicate that inhibition of butyrylcholinesterase (BuChE) is important in the treatment of certain dementias. Further testing of this concept requires inhibitors that are both BuChE-selective and robust.N-alkyl derivatives (2, 3, 4) of phenothiazine (1) have previously been found to inhibit only BuChE in a mechanism involving pi-pi interaction between the phenothiazine tricyclic ring system and aromatic residues in the active site gorge. To explore features of phenothiazines that affect the selectivity and potency of BuChE inhibition, a series of N-carbonyl derivatives (5-25) was synthesized and examined for the ability to inhibit cholinesterases.Some of the synthesized derivatives also inhibited AChE through a different mechanism involving carbonyl interaction within the active site gorge. Binding of these derivatives takes place within the gorge, since this inhibition disappears when the molecular volume of the derivative exceeds the estimated active site gorge volume of this enzyme. In contrast, BuChE, with a much larger active site gorge, exhibited inhibition that increased directly with the molecular volumes of the derivatives. This study describes two distinct mechanisms for binding phenothiazine amide derivatives to BuChE and AChE. Molecular volume was found to be an important parameter for BuChE-specific inhibition. (C) 2004 Elsevier Ltd. All rights reserved.
• Cauquil; Casadrevall, Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1953, vol. 236, p. 1569
  作者：Cauquil、Casadrevall

  DOI：——

  日期：——
• Cauquil; Casadevall, Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1955, vol. 240, p. 538
  作者：Cauquil、Casadevall

  DOI：——

  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.
• Phenothiazine Inhibitors of Trypanothione Reductase as Potential Antitrypanosomal and Antileishmanial Drugs
  作者：Cecil Chan、Hong Yin、Jacqui Garforth、James H. McKie、Rabih Jaouhari、Peter Speers、Kenneth T. Douglas、Peter J. Rock、Vanessa Yardley、Simon L. Croft、Alan H. Fairlamb

  DOI：10.1021/jm960814j

  日期：1998.1.1

  as lead structures for the development of inhibitors, selective for trypanothione reductase over host glutathione reductase. From a homology-modeled structure for trypanothione reductase, replaced in the later stages of the study by the X-ray coordinates for the enzyme from Crithidia fasciculata, a series of inhibitors based on phenothiazine was designed. These were shown to be reversible inhibitors

  鉴于锥虫硫磷在致病性锥虫和利什曼原虫的氧化还原防御中的作用，与谷胱甘肽作为哺乳动物宿主相比，锥虫硫磷还原酶的选择性抑制剂是对抗锥虫病和利什曼病的潜在药物。在本研究中，合理的药物设计方法被用于发现三环抗精神病药物分子框架，作为开发抑制剂的先导结构，对宿主的谷胱甘肽还原酶具有选择性的锥虫硫醇还原酶选择性。根据锥虫还原酶的同源模型结构，在研究的后期阶段，用Crisidia fasciculata的酶的X射线坐标代替，设计了一系列基于吩噻嗪的抑制剂。这些物质被证明是克氏锥虫中锥虫硫醇还原酶的可逆抑制剂，与锥虫硫磷作为底物线性竞争，与NADPH不竞争，这与乒乓球的bi bi动力学一致。合成以定义活性位点的结构-活性关系的类似物包括N-酰基吡嗪，2-取代的吩噻嗪和三取代的丙嗪。根据计算出的log P和摩尔折光率值对Ki和I50数据进行分析，提供了特别有利的小2-取代基（尤其是2-氯和2-三氟甲基）与酶