2-[(2-naphthylsulfonyl)amino]-1,3-thiazol-4-yl-acetic acid ethyl ester | 331435-11-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[(2-naphthylsulfonyl)amino]-1,3-thiazol-4-yl-acetic acid ethyl ester
• 英文别名: ethyl {2-[(2-naphthylsulfonyl)amino]-1,3-thiazol-4-yl}acetate；ethyl 2-[2-(naphthalen-2-ylsulfonylamino)-1,3-thiazol-4-yl]acetate
• CAS: 331435-11-1
• 化学式: C₁₇H₁₆N₂O₄S₂
• 分子量: 376.457
• InChiKey: JJWLUBGKRMKXNK-UHFFFAOYSA-N

物化性质

• 熔点：
  159-160 °C(Solv: ethanol (64-17-5))
• 沸点：
  568.1±42.0 °C(Predicted)
• 密度：
  1.422±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 2-[(2-naphthylsulfonyl)amino]-1,3-thiazol-4-yl-acetic acid ethyl ester 在 aluminum (III) chloride 作用下， 以 甲苯 为溶剂， 反应 0.25h， 以70%的产率得到N-[4-(2-oxo-2-pyrrolidin-1-ylethyl)-1,3-thiazol-2-yl]naphthalene-2-sulfonamide
  参考文献：
  名称：

  Synthesis of 2-{2-[(α/β-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl} acetamides with 11β-hydroxysteroid dehydrogenase inhibition and in combo antidiabetic activities

  摘要：

  Compounds 1-10 were designed using a bioisosteric approach and were prepared using a short synthetic route. The in vitro inhibitory activity of the compounds against 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) was evaluated. Compounds 5 (alpha-series) and 10 (beta-series) had a moderate inhibitory enzyme activity (55.26% and 67.03% inhibition at 10 mu M, respectively) and were as active as BVT.14225 (positive control). Both compounds have a piperidine ring in their structure, but the most active (10) was selected to establish its in vivo antidiabetic effect using a non insulin-dependent diabetes mellitus rat model. The antidiabetic activity of compound 10 was determined at 50 mg/kg single dose in an acute model, and also by short term sub-chronic administration for 5 days. The results indicated a significant decrease of plasma glucose levels, similar than BVT.14225. Additionally, a molecular docking of the most active compounds of each series into the ligand binding pocket of one subunit of human 11 beta-HSD1 was performed. In this model the oxygen atom of the sulfonamide make hydrogen bond interactions with the catalytic residues Ser170 and Ala172. We also observed important pi-pi interactions between the naphthyl group and Tyr177. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.042
• 作为产物：
  描述：

  2-氨基-4-噻唑乙酸乙酯 、 2-萘磺酰氯 在 吡啶 作用下， 以71%的产率得到2-[(2-naphthylsulfonyl)amino]-1,3-thiazol-4-yl-acetic acid ethyl ester
  参考文献：
  名称：

  具有抗血小板活性的新型 2-氨基-噻唑-4-乙酰胺

  摘要：

  在 Born 试验中，合成了 23 种标题化合物，并研究了它们对作为聚集诱导剂的胶原蛋白、ADP、肾上腺素和血小板激活因子 (PAF) 的抗血小板活性。使用胶原蛋白，发现了三种 IC50 值低于 10 μM 的化合物（3a、3b、3c），并确定了 15 种 IC50 值在 10 到 100 μM 之间的化合物。一般来说，环己氨基位于 4-甲酰胺部分是这种药理活性的先决条件。观察到结构元素 Y 中取代基 R1 的明显依赖性。4-甲酰胺取代基中的间隔n也是如此。化合物 3e 显示出强烈的 ADP 拮抗作用（IC50 = 2.2 nM）；3c 拮抗肾上腺素 (IC50 = 2.8 nM)，而 3n 对血小板激活因子非常有效 (IC50 = 0.2 μM)。

  DOI：

  10.1002/ardp.200700046

文献信息

• New 2-Amino-thiazole-4-acetamides with Antiplatelet Activity
  作者：Klaus Rehse、Tobias Baselt

  DOI：10.1002/ardp.200700046

  日期：2008.10

  In the Born test, 23 title compounds were synthesized and investigated for their antiplatelet activities against collagen, ADP, adrenaline, and platelet‐activating factor (PAF) as inducers of the aggregation. Using collagen, three compounds with IC50 values below 10 μM were found (3a, 3b, 3c) and 15 compounds with IC50 values between 10 and 100 μM were determined. In general, a cyclohexylamino rest

  在 Born 试验中，合成了 23 种标题化合物，并研究了它们对作为聚集诱导剂的胶原蛋白、ADP、肾上腺素和血小板激活因子 (PAF) 的抗血小板活性。使用胶原蛋白，发现了三种 IC50 值低于 10 μM 的化合物（3a、3b、3c），并确定了 15 种 IC50 值在 10 到 100 μM 之间的化合物。一般来说，环己氨基位于 4-甲酰胺部分是这种药理活性的先决条件。观察到结构元素 Y 中取代基 R1 的明显依赖性。4-甲酰胺取代基中的间隔n也是如此。化合物 3e 显示出强烈的 ADP 拮抗作用（IC50 = 2.2 nM）；3c 拮抗肾上腺素 (IC50 = 2.8 nM)，而 3n 对血小板激活因子非常有效 (IC50 = 0.2 μM)。
• Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
  申请人：——

  公开号：US20040224996A1

  公开（公告）日：2004-11-11

  The present invention relates to compounds with the formula (II) and also to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds in medicine and for the preparation of a medicament which acts on the human 11-&bgr;-hydroxysteroid dehydrogenase type 1 enzyme. 1

  本发明涉及式（II）的化合物，以及包含该化合物的制药组合物，其制备过程，以及在医学上使用该化合物以及用于制备对人体11-β-羟基类固醇脱氢酶1型酶起作用的药物。
• INHIBITORS OF 11-BETA-HYDROXY STERIOD DEHYDROGENASE TYPE 1
  申请人：BARF Tjeerd

  公开号：US20100113435A1

  公开（公告）日：2010-05-06

  The present invention relates to compounds with the formula (II) and also to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds in medicine and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme.

  本发明涉及公式（II）的化合物，以及包含这些化合物的制药组合物，它们的制备过程，以及这些化合物在医学上的使用和用于制备对人类11-β-羟基类固醇脱氢酶1型酶起作用的药物。
• Synthesis of 2-{2-[(α/β-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl} acetamides with 11β-hydroxysteroid dehydrogenase inhibition and in combo antidiabetic activities
  作者：Gabriel Navarrete-Vázquez、Maria Guadalupe Morales-Vilchis、Samuel Estrada-Soto、Juan José Ramírez-Espinosa、Sergio Hidalgo-Figueroa、Carlos Nava-Zuazo、Hugo Tlahuext、Ismael Leon-Rivera、José L. Medina-Franco、Fabian López-Vallejo、Scott P. Webster、Margaret Binnie、Rolffy Ortiz-Andrade、Hermenegilda Moreno-Diaz

  DOI：10.1016/j.ejmech.2013.12.042

  日期：2014.3

  Compounds 1-10 were designed using a bioisosteric approach and were prepared using a short synthetic route. The in vitro inhibitory activity of the compounds against 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) was evaluated. Compounds 5 (alpha-series) and 10 (beta-series) had a moderate inhibitory enzyme activity (55.26% and 67.03% inhibition at 10 mu M, respectively) and were as active as BVT.14225 (positive control). Both compounds have a piperidine ring in their structure, but the most active (10) was selected to establish its in vivo antidiabetic effect using a non insulin-dependent diabetes mellitus rat model. The antidiabetic activity of compound 10 was determined at 50 mg/kg single dose in an acute model, and also by short term sub-chronic administration for 5 days. The results indicated a significant decrease of plasma glucose levels, similar than BVT.14225. Additionally, a molecular docking of the most active compounds of each series into the ligand binding pocket of one subunit of human 11 beta-HSD1 was performed. In this model the oxygen atom of the sulfonamide make hydrogen bond interactions with the catalytic residues Ser170 and Ala172. We also observed important pi-pi interactions between the naphthyl group and Tyr177. (C) 2014 Elsevier Masson SAS. All rights reserved.