2-chloro-N-(3-bromopropyl)aminophenothiazine | 59958-21-3

• 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: 2-chloro-N-(3-bromopropyl)aminophenothiazine
• 英文别名: 1-(3-bromopropyl)-2-chlorophenothiazine；10-(3-Bromopropyl)-2-chloro-phenothiazine；10-(3-bromopropyl)-2-chlorophenothiazine
• CAS: 59958-21-3
• 化学式: C₁₅H₁₃BrClNS
• 分子量: 354.698
• InChiKey: UFSZBJAZFWJXFD-UHFFFAOYSA-N

物化性质

• 沸点：
  466.2±45.0 °C(Predicted)
• 密度：
  1.504±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  19
• 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：
  28.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(3-bromopropyl)aminophenothiazine 在 sodium t-butanolate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  附加的吩噻嗪对胸腺嘧啶环丁烷二聚体光敏裂解的溶剂影响

  摘要：

  拴系发色团分裂二聚体的量子产率表现出不同的溶剂效应。为了进一步探索溶剂作用的机理，制备了三种具有短连接基1a - 1c的共价连接的吩噻嗪-二聚体模型化合物。据观察，溶剂对吩噻嗪-二聚体系统的二聚体拆分效率的影响与其他生色团-二聚体系统相反。基于该理论马库斯计算结果显示出与由较低值引起较低的驱动力嗪系统Ë OX有吩噻嗪部分和二聚体单元之间的较长供体-受体距离，然后给出一个较高的λ小号。因此，对于吩噻嗪-二聚体模型，反向电子传递将位于Marcus正常区域，在该模型中，二聚体拆分在更高极性的溶剂中更为有效。供体和受体之间氧化还原电势的值应该是导致不同马库斯区域中发生反向电子转移并遵循两个反向溶剂效应的关键。此外，荧光光谱显示双重荧光给出了电荷转移配合物的提示，并且部分电荷转移将导致较低的分裂效率。然而，获得了一些新的见解，了解了由光解酶介导的DNA光活化的机制。

  DOI：

  10.1016/j.jphotochem.2012.07.014
• 作为产物：
  描述：

  2-氯吩噻嗪 在 硼烷 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 2.67h， 生成 2-chloro-N-(3-bromopropyl)aminophenothiazine
  参考文献：
  名称：

  Use of an Additional Hydrophobic Binding Site, the Z Site, in the Rational Drug Design of a New Class of Stronger Trypanothione Reductase Inhibitor, Quaternary Alkylammonium Phenothiazines

  摘要：

  Improved rationally designed lead drug structures against African trypanosomiasis, Chagas disease, and leishmaniasis were obtained against trypanothione reductase from Trypanosoma cruzi. Substituted-benzyl [3-(2-chloro-4a,10a-dihydrophenothiazin-10-yl)propyl] dimethyl ammonium salts, synthesized by Menschutkin quaternization of the tertiary alkylamine omega-nitrogen atom of chlorpromazine, were linear, competitive inhibitors of recombinant trypanothione reductase from T. cruzi, with either trypanothione disulfide or N-benzyloxycarbonyl-L-cysteinylglycyl 3-dimethylaminopropylamide disulfide as substrate. The permanent positive charge on the distal nitrogen atom of the tricyclic side chain contribution to binding was estimated as greater than or equal to 5.6 kcal.mol(-1) by comparison with the analogue with the cationic nitrogen atom of the quaternary replaced by an ether oxygen atom. A further major contribution to improving K-i values and inhibition strength was the hydrophobic natures and structures of the N-benzyl substituents. The strongest inhibitor, the (3-(2-chloro-4a,10a-dihydrophenothiazin-10-yl)propyl]-(3,4-dichlorobenzyl)dimethylammonium derivative (K-i 0.12 mu M), was similar to 2 orders of magnitude more inhibitory than the parent chlorpromazine. Several of these quaternary phenothiazines completely inhibited T. brucei parasite growth in vitro at < 1 mu M Antiparasite activity was not solely determined by inhibition strength against trypanothione reductase, there being a strong contribution from hydrophobicity (for example, benzhydryl-quaternized chlorpromazime had ED50 < 1 mu M). Although active against Leishmania donovani, none of the analogues showed major improvement in this activity relative to chlorpromazine or other nonquaternized phenothiazines. The p-tert-butylbenzyl-quaternized analogue very strongly inhibited (ED50 < 1 mu M) growth of the amastigote stage of T. cruzi.

  DOI：

  10.1021/jm000156+

文献信息

• Phase transfer catalysis in<i>N</i>-alkylation of the pharmaceutical intermediates phenothiazine and 2-chlorophenothiazine
  作者：Igal Gozlan、David Ladkani、Mark Halpern、Mordecai Rabinovitz、David Avnir

  DOI：10.1002/jhet.5570210271

  日期：1984.3

  The N-alkylation of the two title compounds was studied, utilizing phase transfer catalysis (PTC) methods. Very mild reaction conditions were developed, especially for three-carbon N-alkylation. Of special interest is the high-yield synthesis of N-(3-chloropropyl)-2-chlorophenothiazine. The results are discussed in terms of the classical PTC/OH− mechanisms.

  利用相转移催化（PTC）方法研究了两种标题化合物的N-烷基化。已经开发出非常温和的反应条件，特别是对于三碳N-烷基化。特别令人感兴趣的是N-（3-氯丙基）-2-氯吩噻嗪的高产率合成。结果列于经典PTC / OH来讨论-机制。
• Inhibition of RNA function
  申请人：The Regents of the University of California

  公开号：US20030229082A1

  公开（公告）日：2003-12-11

  Inhibition of RNA function, and treatment or control of diseases or conditions, e.g. infectious diseases such as viruses and viral infections (including HIV) and microbial infections, by the contacting of the RNA with a compound having a central or core structure comprising three fused rings containing from 12 to 15 ring atoms, the central ring including at least one heteroatom selected from nitrogen, oxygen and sulfur, the atoms of the three-ring core structure being optionally substituted with substituents such as halogens, cyano, and/or various substituted or unsubstituted aliphatic and/or heteroaliphatic moieties, or contacting the RNA with yohimbine, usnic acid or N-{4-[2,5-Dioxo-1-(4-trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-phenyl}-2,2,2-trifluoro-acetamide. Preferred compounds are various phenothiazines, including both known and novel compounds.

  抑制RNA功能，并通过将RNA与含有由12至15个环原子的三个融合环组成的中心或核结构的化合物接触，来治疗或控制疾病或病况，例如传染病如病毒和病毒感染（包括HIV）以及微生物感染，其中中心环至少包括一种氮、氧或硫等杂原子，三环核结构的原子可选择性地取代为卤素、氰基和/或各种取代或未取代的脂肪和/或杂原脂肪基，或者将RNA与鹿胶碱、乌斯尼酸或N-[4-(2,5-二氧代-1-(4-三氟甲氧基苯基)-吡咯啉-3-基)-苯基]-2,2,2-三氟乙酰胺接触。优选的化合物包括各种吩噻嗪，包括已知和新颖的化合物。
• 一种诱导肿瘤干细胞焦亡的诊疗前药及其制备方法和应用
  申请人：东南大学

  公开号：CN118105488A

  公开（公告）日：2024-05-31

  本发明公开了一种诱导肿瘤干细胞焦亡的诊疗前药极其制备方法和应用，是用吩噻嗪类药物修饰的聚集诱导发光光敏剂，应用在诱导肿瘤干细胞焦亡和/或治疗肿瘤和/或抑制肿瘤生长和/或免疫激活的药物中。所述单诊疗前药具有优异的近红外聚集诱导发光能力，其在成像和光免疫治疗方面具有更大的潜力；以及具有可快速靶向线粒体，并在线粒体逃逸后与溶酶体重叠，引起双细胞器功能障碍的能力，是一种很有前途的光诱导肿瘤干细胞焦亡和免疫激活的候选材料。激活肿瘤干细胞死亡通路PP2A/c‑myc/p21，并具有全身抗肿瘤作用。本发明能实现细胞焦亡介导的光动力和光热协同免疫治疗，防止免疫逃逸来消除肿瘤和防止肿瘤转移。
• HAWES, E. M.;GURNSEY, T. S.;SHETTY, H. U.;MIDHA, K. K., J. LABELLED COMPOUNDS AND RADIOPHARM., 1983, 20, N 6, 757-769
  作者：HAWES, E. M.、GURNSEY, T. S.、SHETTY, H. U.、MIDHA, K. K.

  DOI：——

  日期：——
• MISIMA, YUTAKA;NAKAGAVA, TOSIO;AONO, KATSUTOSI
  作者：MISIMA, YUTAKA、NAKAGAVA, TOSIO、AONO, KATSUTOSI

  DOI：——

  日期：——