2-amino-4-methyl-naphtho[1,2-d]thiazol-5-ol | 26269-05-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并噻唑类
• 英文名称: 2-amino-4-methyl-naphtho[1,2-d]thiazol-5-ol
• 英文别名: 2-Amino-5-hydroxy-4-methylnaphtho<1,2-d>thiazole；2-Amino-4-methylnaphtho[1,2-d]thiazol-5-ol；2-amino-4-methylbenzo[e][1,3]benzothiazol-5-ol
• CAS: 26269-05-6
• 化学式: C₁₂H₁₀N₂OS
• 分子量: 230.29
• InChiKey: RMVGXVZNNGLSBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  87.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-4-methyl-naphtho[1,2-d]thiazol-5-ol 在 乙酸铵 、 sodium tetrahydroborate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 8.0h， 生成 4-Methyl-2-(pyridin-3-ylmethylamino)benzo[e][1,3]benzothiazol-5-ol
  参考文献：
  名称：

  Novel Dual Inhibitors of 5-Lipoxygenase and Thromboxane A2 Synthetase: Synthesis and Structure-Activity Relationships of 3-Pyridylmethyl-Substituted 2-Amino-6-hydroxybenzothiazole Derivatives

  摘要：

  As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B-4 (LTB(4)) and thromboxane A(2) (TXA(2)), while not significantly inhibiting that of prostaglandin E(2) (PGE(2)). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-Lipoxygenase and TXA(2) synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE(2) production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA(2) synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA(2) synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/ kg), the production of both LTB(4) and TXB(2) in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4 zole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.

  DOI：

  10.1021/jm00045a011
• 作为产物：
  描述：

  甲萘醌 、 硫脲 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以28%的产率得到2-amino-4-methyl-naphtho[1,2-d]thiazol-5-ol
  参考文献：
  名称：

  Synthesis, Cytotoxicity andIn VitroAntileishmanial Activity of Naphthothiazoles

  摘要：

  The leishmaniasis is a spectral disease caused by the protozoan Leishmania spp., which threatens millions of people worldwide. Current treatments exhibit high toxicity, and there is no vaccine available. The need for new lead compounds with leishmanicidal activity is urgent. Considering that many lead leishmanicidal compounds contain a quinoidal scaffold and the thiazole heterocyclic ring is found in a number of antimicrobial drugs, we proposed a hybridization approach to generate a diverse set of semi‐synthetic heterocycles with antileishmanial activity. We found that almost all synthesized compounds demonstrated potent activity against promastigotes of Leishmania (Viannia) braziliensis and reduced the survival index of Leishmania amastigotes in mammalian macrophages. Furthermore, the compounds were not cytotoxic to macrophages at fivefold higher concentrations than the EC50 for promastigotes. All molecules fulfilled Lipinski's Rule of Five, which predicts efficient orally absorption and permeation through biological membranes, the in silico pharmacokinetic profile confirmed these characteristics. The potent and selective activity of semi‐synthetic naphthothiazoles against promastigotes and amastigotes reveals that the 2‐amino‐naphthothiazole ring may represent a scaffold for the design of compounds with leishmanicidal properties and encourage the development of drug formulation and new compounds for further studies in vivo.

  DOI：

  10.1111/cbdd.12123

文献信息

• Anti-malarial compounds, compositions and methods
  申请人：——

  公开号：US20030186993A1

  公开（公告）日：2003-10-02

  The present invention is directed to substituted naphthothiazolium, aromatic guanylhydrazones, and other compounds and compositions with anti-malarial activity useful for the treatment and prophylaxis of malaria. The compounds are provided for the treatment of malaria or the sequelae of malarial infection, for depolymerizing malaria pigment (hemozoin), and for ameliorating the adverse effects of hemozoin on host cells.

  本发明涉及替代萘并噻唑、芳香基胍脲和其他具有抗疟活性的化合物和组合物，适用于治疗和预防疟疾。这些化合物可用于治疗疟疾或疟疾感染的后遗症，用于降解疟原色素（血红素），并用于改善疟原色素对宿主细胞的不良影响。
• Reaction of quinones with thiourea. Novel route to 2-amino-6-hydroxybenzothiazoles and 2-amino-5-hydroxynaphtho[1,2-d] thiazoles
  作者：Philip T. S. Lau、T. E. Compf

  DOI：10.1021/jo00837a003

  日期：1970.12
• US6689777B2
  申请人：——

  公开号：US6689777B2

  公开（公告）日：2004-02-10
• Novel Dual Inhibitors of 5-Lipoxygenase and Thromboxane A2 Synthetase: Synthesis and Structure-Activity Relationships of 3-Pyridylmethyl-Substituted 2-Amino-6-hydroxybenzothiazole Derivatives
  作者：Shigeki Hibi、Yasushi Okamoto、Katsuya Tagami、Hirotoshi Numata、Naoki Kobayashi、Masanobu Shinoda、Tetsuya Kawahara、Manabu Murakami、Kiyoshi Oketani

  DOI：10.1021/jm00045a011

  日期：1994.9

  As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B-4 (LTB(4)) and thromboxane A(2) (TXA(2)), while not significantly inhibiting that of prostaglandin E(2) (PGE(2)). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-Lipoxygenase and TXA(2) synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE(2) production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA(2) synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA(2) synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/ kg), the production of both LTB(4) and TXB(2) in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4 zole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.
• Synthesis, Cytotoxicity and<i>In Vitro</i>Antileishmanial Activity of Naphthothiazoles
  作者：Juliano S. de Toledo、Paulo E. S. Junior、Viviane Manfrim、Camila F. Pinzan、Alexandre S. de Araujo、Angela K. Cruz、Flavio S. Emery

  DOI：10.1111/cbdd.12123

  日期：2013.6

  The leishmaniasis is a spectral disease caused by the protozoan Leishmania spp., which threatens millions of people worldwide. Current treatments exhibit high toxicity, and there is no vaccine available. The need for new lead compounds with leishmanicidal activity is urgent. Considering that many lead leishmanicidal compounds contain a quinoidal scaffold and the thiazole heterocyclic ring is found in a number of antimicrobial drugs, we proposed a hybridization approach to generate a diverse set of semi‐synthetic heterocycles with antileishmanial activity. We found that almost all synthesized compounds demonstrated potent activity against promastigotes of Leishmania (Viannia) braziliensis and reduced the survival index of Leishmania amastigotes in mammalian macrophages. Furthermore, the compounds were not cytotoxic to macrophages at fivefold higher concentrations than the EC50 for promastigotes. All molecules fulfilled Lipinski's Rule of Five, which predicts efficient orally absorption and permeation through biological membranes, the in silico pharmacokinetic profile confirmed these characteristics. The potent and selective activity of semi‐synthetic naphthothiazoles against promastigotes and amastigotes reveals that the 2‐amino‐naphthothiazole ring may represent a scaffold for the design of compounds with leishmanicidal properties and encourage the development of drug formulation and new compounds for further studies in vivo.