1,2-dihydropyrrolo[3,2,1-kl]-phenothiazin-1,2-dione | 29939-43-3

• 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: 1,2-dihydropyrrolo[3,2,1-kl]-phenothiazin-1,2-dione
• 英文别名: 8-Thia-1-azatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16)-hexaene-14,15-dione
• CAS: 29939-43-3
• 化学式: C₁₄H₇NO₂S
• 分子量: 253.281
• InChiKey: INDCRUMWKNDWRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-dihydropyrrolo[3,2,1-kl]-phenothiazin-1,2-dione 在 五氯化磷 、 sodium hydride 、 溶剂黄146 、 锌 作用下， 以 甲苯 、 苯 为溶剂， 反应 12.0h， 生成 1,2-dihydro-N-phenyl-1-oxopyrrolo[3,2,1-kl]phenothiazine-2-carboxamide
  参考文献：
  名称：

  1,2-二氢-1-氧代吡咯并[3,2,1-kl]吩噻嗪-2-羧酰胺和同类物，具有抗炎活性的双重环氧合酶/ 5-脂氧合酶抑制剂。

  摘要：

  一系列1,2-二氢-1-氧杂吡咯[3,2,1-kl]吩噻嗪，1,2-二氢-1-氧杂吡咯[3,2,1-kl]吩恶嗪和1,2-二氢- 1-氧代吡咯并[3,2,1-去] ac啶-2-羧酰胺是通过1,2-二氢-1-氧代-吡咯并[3,2,1-kl]吩噻嗪或其他相应的吩恶嗪与a啶乙基的反应制得的或带有适当胺的甲酯。发现该家族的几个成员是花生四烯酸代谢的有效的环氧合酶和5-脂氧合酶的双重抑制剂，并且在大鼠足水肿试验中具有体内抗炎活性。描述了该化合物家族中的构效关系。1,2-二氢-N-（2-噻唑基）-1-氧吡咯并[3,2，发现1-kl]吩噻嗪-1-羧酰胺（34）是表现出有效的环氧合酶/ 5-脂氧合酶抑制花生四烯酸代谢的最佳化合物之一。它对源自大鼠嗜碱性粒细胞白血病1（RBL-1）细胞的酶的IC50分别为0.07和1.4 microM。它在大鼠足部水肿试验中具有抗炎作用（在33 mg / kg口服时抑制48

  DOI：

  10.1021/jm00169a035
• 作为产物：
  描述：

  吩噻嗪 以40%的产率得到1,2-dihydropyrrolo[3,2,1-kl]-phenothiazin-1,2-dione
  参考文献：
  名称：

  Class of spiro-linked pyrrolidine-2,5-diones

  摘要：

  该发明提供了一种新颖的螺环联接的吡咯烷-2,5-二酮，其化学式为：##STR1## 其中X.sub.1和X.sub.2各自独立地代表氢、卤原子、低碳基或低碳氧基；Y代表亚甲基、氧原子或硫原子；R.sub.1、R.sub.2、R.sub.3和R.sub.4各自独立地代表氢原子、低碳基或与其相邻碳原子共同形成苯环；其与药学上可接受的阳离子形成的盐和其制备方法。还公开了化合物的化学式[I]，用作醛糖还原酶抑制剂和治疗慢性糖尿病并发症的治疗剂。

  公开号：

  US04593092A1

文献信息

• The reaction of 1,2-dioxo-1,2-dihydropyrrolo-[3,2,1-<i>kl</i>] phenothiazine with amines
  作者：Ângelo C. Pinto、Richard A. Hollins

  DOI：10.1002/jhet.5570140428

  日期：1977.6

  The title compound I reacts with aliphatic amines producing ring-opened keto-amides of structure VII and with anilines forming imines of structure VIII.

  标题化合物I与脂族胺反应，生成结构VII的开环酮酰胺，并与苯胺形成结构VIII的亚胺。
• A simple synthesis of 1-phenothiazineethanolamines: Potential antimalarials
  作者：Ângelo C. Pinto、Rosaly S. Da Silva、Richard A. Hollins

  DOI：10.1002/jhet.5570160554

  日期：1979.7

  Two routes for the synthesis of the 1-phenothiazineethanolamine (4) starting from 1,2-dioxo-1,2-dihydropyrrolo[3,2,1-kl]phenothiazine are described.

  描述了从1,2-二氧代-1,2-二氢吡咯并[3,2,1- kl ]吩噻嗪开始的1-吩噻嗪乙醇胺（4）的两种合成途径。
• Synthesis, antiproliferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives
  作者：Valérie Verones、Nathalie Flouquet、Marie Lecoeur、Amelie Lemoine、Amaury Farce、Brigitte Baldeyrou、Christine Mahieu、Nicole Wattez、Amélie Lansiaux、Jean-François Goossens、Pascal Berthelot、Nicolas Lebegue

  DOI：10.1016/j.ejmech.2012.10.051

  日期：2013.1

  The synthesis of new acridinone and dioxophenothiazine derivatives along with their tubulin polymerization inhibitory and antiproliferative activities is reported. The analysis of correlation for cytotoxic and antitubulin potential of tested compounds showed that 4-methoxyphenylethyl derivatives 18a and 19a were highly cytotoxic but were regarded to have no significant antitubulin activity. However, the introduction of a 3-hydroxy substituent leading to compounds 18e and 19e, strongly increased the antitubulin potential but was associated with a loss of the antiproliferative activity. Modeling studies, topoisomerase inhibition assays and cell cycle analysis have been performed to better investigate the mechanism of action of such compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.
• New class of potent antinociceptive and antiplatelet 10H-phenothiazine-1-acylhydrazone derivatives
  作者：Gildásio A. Silva、Luciana M.M. Costa、Fernanda C.F. Brito、Ana L.P. Miranda、Eliezer J. Barreiro、Carlos A.M. Fraga

  DOI：10.1016/j.bmc.2004.04.009

  日期：2004.6

  In this work, we reported the synthesis and evaluation of the analgesic, antiinflammatory, and antiplatelet properties of new phenothiazine-attached acylhydrazone derivatives (6), designed exploring the molecular hybridization approach between antipsychotic chlorpromazine (4) and other heterocyclic derivatives (3) and (5) developed at LASSBio. Target compounds were synthesized in very good yields exploiting diphenylamine (7) as starting material, through regioselective functionalization of the C-1 position of 10H-phenothiazine ring. The evaluation of platelet antiaggregating profile lead us to identify a new potent prototype of antiplatelet derivative, that is (6a) (IC50 = 2.3 muM), which acts in arachidonic acid pathway probably by inhibition of platelet COX-1 enzyme. Additionally, the change of para-substituent group of acylhydrazone framework permitted us to identify hydrophilic carboxylate derivative (6g) and hydrophobic bromo derivative (66) as two new leads of analgesics more active than dipyrone used as standard and with selective peripheral or central mechanism of action. (C) 2004 Elsevier Ltd. All rights reserved.
• PINTO A. C.; SILVA R. S. DA; HOLLINS R. A., J. HETEROCYCL. CHEM., 1979, 16, NO 5, 1085-1086
  作者：PINTO A. C.、 SILVA R. S. DA、 HOLLINS R. A.

  DOI：——

  日期：——