3-(10H-phenothiazin-10-yl)propan-1-amine | 2095-21-8

• 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: 3-(10H-phenothiazin-10-yl)propan-1-amine
• 英文别名: 3-phenothiazin-10-ylpropan-1-amine
• CAS: 2095-21-8
• 化学式: C₁₅H₁₆N₂S
• mdl: MFCD08694851
• 分子量: 256.371
• InChiKey: OJPDZEFBOMRMTK-UHFFFAOYSA-N

物化性质

• 熔点：
  226-228 °C
• 沸点：
  416.3±34.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(10H-phenothiazin-10-yl)propan-1-amine 在 氢溴酸 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 1.5h， 生成 (RS)-4-N-[3-(phenothiazin-10-yl)propan-1-yl]amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol hydrobromide
  参考文献：
  名称：

  Selective inhibitors of GABA uptake: synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues

  摘要：

  A series of lipophilic diaromatic derivatives of the glia-selective GABA uptake inhibitor (R)-4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol [(R)-exo-THPO, 4] were synthesized via reductive amination of 3-ethoxy-4,5,6,7-tetrahydrobenzo[d]isoxazol-4-one (9) or via N-alkylation of O-alkylatedracemic 4. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation or primary cultures of mouse cortical neurons and glia cells (astrocytes), as well as HEK cells transfected with cloned mouse GABA transporter subtypes (GAT1-4). The activity against isoniazid-induced convulsions in mice after subcutaneous administration of the compounds was determined. All of the compounds were potent inhibitors of synaptosomal uptake the most potent compound being (RS)-4-[N-(1,1-diphenylbut-1-4-en-yl)amino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (17a, IC50 = 0.14 muM). The majority of the compounds showed a weak preference for glial, as compared to neuronal, GABA uptake. The highest degree of selectivity was 10-fold corresponding to the glia selectivity of (R)-N-methyl-exo-THPO (5). All derivatives showed a preference for the GAT1 transporter, as compared with GAT2-4, with the exception of (RS)-4-[N-[1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (28d), which quite surprisingly turned out to be more potent than GABA at both GAT1 and GAT2 subtypes. The GAT1 activity was shown to reside in (R)-28d whereas (R)-28d and (S)-28d contributed equally to GAT2 activity. This makes (S)-28d a GAT2 selective compound, and (R)-28d equally effective in inhibition of GAT1 and GAT2 mediated GABA transport. All compounds tested were effective as anticonvulsant reflecting that these compounds have blood-brain barrier permeating ability. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.029
• 作为产物：
  描述：

  吩噻嗪 在 三乙基硅烷 、 水 、 三氟乙酸 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-(10H-phenothiazin-10-yl)propan-1-amine
  参考文献：
  名称：

  吩噻嗪-他林异二聚体：在阿尔茨海默氏病中采用多靶点定向方法

  摘要：

  自2002年以来，没有针对阿尔茨海默氏病的临床候选药物上市。因此，迫切需要一种有效的治疗方法。我们遵循所谓的“多靶标定向配体”方法，设计了36种新型他克林-吩噻嗪异二聚体，并对其体外抗胆碱酯酶特性进行了评估。对这类衍生物的构效关系的评估突出了化合物1dC作为有效的选择性乙酰胆碱酯酶抑制剂，IC 50 = 8 nM，1aA作为有效的丁酰胆碱酯酶抑制剂，IC 50 = 15 nM。选定的杂种，即1aC，1bC，1cC，1dC和2dC表现出对τ （306-336）肽聚集的显着抑制活性，抑制百分比范围为50.5至62.1％。同样，1dC和2dC具有抑制自诱导的Aβ1–42聚集的显着能力。尽管如此，体外研究显示对HepG2细胞和小脑颗粒神经元具有细胞毒性。当以14 mg / kg（ip）对小鼠施用1dC时，未观察到病理生理异常。如体外和体内模型所示，1dC还能够渗透到CNS中。最大大脑浓度接近IC乙

  DOI：

  10.1021/acschemneuro.1c00184

文献信息

• [EN] INHIBITORS OF MALT1 PROTEASE<br/>[FR] INHIBITEURS DE LA PROTÉASE MALT1
  申请人：HELMHOLTZ ZENTRUM MÜNCHEN DEUTSCHES FORSCHUNGSZENTRUM FÜR GESUNDHEIT UND UMWELT GMBH

  公开号：WO2014086478A1

  公开（公告）日：2014-06-12

  The present invention relates to compounds which are inhibitors of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALTl) and to their use in therapy, in particular in the treatment or prevention of a disease or disorder which is treatable by an inhibitor of a paracaspase. The present invention also relates to pharmaceutical compositions containing such compounds.

  本发明涉及作为粘膜相关淋巴组织淋巴瘤易位蛋白1（MALT1）抑制剂的化合物及其在治疗中的应用，尤其是在治疗或预防可通过抑制paracaspase治疗的疾病或失调中的应用。本发明还涉及含有该化合物的药物组合物。
• Phenothiazine electrophores immobilized on periodic mesoporous organosilicas by ion exchange
  作者：Björn Schäfgen、Hilla Khelwati、Dominique F. Bechtel、Annelies DeCuyper、Axel Schüssler、Adam Neuba、Antonio J. Pierik、Stefan Ernst、Thomas J. J. Müller、Werner R. Thiel

  DOI：10.1039/c9nj04661e

  日期：——

  groups in the side chain have been synthesized and fully characterized. These compounds were immobilized by ion exchange on the surface of a periodic mesoporous organosilica (PMO) and a neat silica SBA-15 material bearing sulphonate groups covalently bound to the pore surface. The resulting porous and electrochromophoric materials were studied by means of solid state CP-MAS NMR, IR, UV/Vis and fluorescence

  合成并充分表征了两种不同的在侧链上带有季铵基的吩噻嗪。这些化合物通过离子交换固定在周期性介孔有机二氧化硅（PMO）和带有共价键合到孔表面的带有磺酸盐基团的纯净二氧化硅SBA-15材料上。通过固态CP-MAS NMR，IR，UV / Vis和荧光光谱，氮吸附/解吸测量和循环伏安法研究所得的多孔和电致变色材料。与载体的性质无关，这些材料的颜色在光照射下变为粉红色，表明形成了吩噻嗪自由基阳离子。这些物质即使在存在大气氧气的情况下也具有很高的稳定性，并通过EPR光谱进行了表征。
• Evidence of preferential π-stacking: a study of intermolecular and intramolecular charge transfer complexes
  作者：N. S. Saleesh Kumar、Maneesh D. Gujrati、James N. Wilson

  DOI：10.1039/c0cc00249f

  日期：——

  Nine combinations of pi-electron donors and acceptors were examined by UV-vis, fluorescence and (1)H-NMR spectroscopy to identify pi-stacked charge transfer complexes in macromolecular and supramolecular constructs. The high association constant of pyrene and naphthalene diimide suggests a preferentially pi-stacking pair rationalized by frontier orbital congruence.

  通过紫外可见，荧光和（1）H-NMR光谱检查了pi电子供体和受体的九种组合，以鉴定大分子和超分子构建体中pi堆积的电荷转移复合物。and和萘二酰亚胺的高缔合常数表明，优先选择的pi堆积对通过边际轨道全合合理化。
• A Fast and Parallel Route to Cyclic Isothioureas and Guanidines with Use of Microwave-Assisted Chemistry
  作者：Helena Sandin、Marie-Louise Swanstein、Eric Wellner

  DOI：10.1021/jo030338m

  日期：2004.3.1

  is achieved solely by the application of microwave-assisted chemistry, without any need of activating agents or protecting group manipulations. The product formation of various substituted guanidines from the corresponding isothiouronium salts was controlled by the nucleophilicity of the counterion and influenced by the reaction temperature. Further, a new fast-track access to tetrahydropyrimidin-2-ylamines

  在这项研究中提出了一种快速，简单的方法来新颖的环状异硫脲和相关的胍衍生物。仅通过微波辅助化学的应用即可完成中央碱性支架的构建，而无需任何活化剂或保护基团的操作。由相应的异硫脲鎓盐形成的各种取代的胍的产物形成受抗衡离子的亲核性控制，并受反应温度的影响。此外，开发了对四氢嘧啶-2-基胺的新的快速通道。
• Photoinduced electron transfer in amino acid assemblies
  作者：Sandra L. Mecklenburg、Brian M. Peek、Jon R. Schoonover、Dewey G. McCafferty、Craig G. Wall、Bruce W. Erickson、Thomas J. Meyer

  DOI：10.1021/ja00066a017

  日期：1993.6

  related model compounds based on polypyridyl ruthenium complexes are described. Donor-chromophore-acceptor triad 1, [PTZpn-Lys(Ru II b 2 m) 2+ -NH-prPQ 2+ ] (PF 6 - ) 4 (see below), was prepared by assembly of a modified ruthenium bipyridyl chromophore (Ru II b 2 m, where b=2,2'-bipyridine, m=4'-methyl-2,2'-bipyridyl-4'-carbonyl), an electron donor (phenothiazine, PTZ), and an electron acceptor (paraquat

  描述了一系列基于聚吡啶钌配合物的氧化还原活性赖氨酸和相关模型化合物的制备和光物理表征。供体-发色团-受体三联体 1，[PTZpn-Lys(Ru II b 2 m) 2+ -NH-prPQ 2+ ] (PF 6 - ) 4（见下文），通过组装修饰的钌联吡啶发色团（ Ru II b 2 m，其中 b=2,2'-联吡啶，m=4'-甲基-2,2'-联吡啶-4'-羰基）、电子供体（吩噻嗪，PTZ）和电子受体（百草枯、PQ 2+ ) 在赖氨酸 (Lys) 支架上利用酰胺键