3-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzoic acid | 926230-39-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzoic acid
• 英文别名: 3-{4H,5H,6H,7H-thieno[3,2-c]pyridine-5-sulfonyl}benzoic acid；3-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-ylsulfonyl)benzoic acid
• CAS: 926230-39-9
• 化学式: C₁₄H₁₃NO₄S₂
• mdl: MFCD09050829
• 分子量: 323.394
• InChiKey: KOKBEXZEABMYFP-UHFFFAOYSA-N

物化性质

• 沸点：
  569.0±60.0 °C(Predicted)
• 密度：
  1.493±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.214
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzoic acid 在 硫酸 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 32.0h， 生成 N'-[(E)-(4-chlorophenyl)methylidene]-3-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzohydrazide
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Hydrazone Derivatives Bearing 3-(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzoicacid Scaffold

  摘要：

  本研究描述了从商业可获得的4,5,6,7-四氢噻吩[3,2-c]吡啶（1）合成的3-(6,7-二氢噻吩[3,2-c]吡啶-5(4H)-基磺酰基)苯肼衍生物（7a-p），并研究了其抗菌活性。通过核磁共振（1H NMR）、红外光谱（IR）和质谱分析对合成化合物7a-p进行了表征。这些合成化合物在琼脂孔扩散法下对革兰氏阴性和革兰氏阳性菌株进行了测试，包括：（i）大肠杆菌（MTCC 443）、（ii）铜绿假单胞菌（MTCC 424）、（iii）金黄色葡萄球菌（MTCC 96）和（iv）化脓性链球菌（MTCC 442）。化合物7g（R = 2-OH, 4-OCHF2）、7h（R = 2-NO2）、7i（R = 3-NO2）、7j（R = 4-NO2）和7n（4-OH）对革兰氏阳性和阴性菌株均表现出优异的抗菌活性（抑菌圈直径：25-32毫米）。化合物7f（R = 2-F, 3-Cl）、7k（R = 2-OMe）、7l（R = 4-OMe）、7m（R = 4-OEt）、7o（R = 3-OMe）、7p（R = 3,4-OEt）显示出良好的抗菌活性（抑菌圈直径：19-26毫米）。

  DOI：

  10.14233/ajchem.2015.18877
• 作为产物：
  描述：

  3-氯磺酰基苯甲酸 、 4,5,6,7-四氢噻吩[3,2-c]吡啶盐酸盐 以 丙酮 为溶剂， 以31%的产率得到3-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzoic acid
  参考文献：
  名称：

  3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3

  摘要：

  A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.

  DOI：

  10.1021/jm3007867

文献信息

• 3-(3,4-Dihydroisoquinolin-2(1<i>H</i>)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3
  作者：Stephen M. F. Jamieson、Darby G. Brooke、Daniel Heinrich、Graham J. Atwell、Shevan Silva、Emma J. Hamilton、Andrew P. Turnbull、Laurent J. M. Rigoreau、Elisabeth Trivier、Christelle Soudy、Sharon S. Samlal、Paul J. Owen、Ewald Schroeder、Tony Raynham、Jack U. Flanagan、William A. Denny

  DOI：10.1021/jm3007867

  日期：2012.9.13

  A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.
• Synthesis and Antibacterial Activity of Hydrazone Derivatives Bearing 3-(6,7-Dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzoicacid Scaffold
  作者：Gowrisankar Rao Kaki、B. Sreenivasulu、Aminul Islam、Dussa Nageshwar、Raghubabu Korupolu、B. Venkateshwara Rao

  DOI：10.14233/ajchem.2015.18877

  日期：——

  The present work describes the synthesis and antibacterial activity of 3-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-ylsulfonyl)benzohydrazide derivatives (7a-p) prepared from commercially available 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (1). They were characterized by 1H NMR, IR and mass spectral analysis. The synthesized compounds 7a-p, were tested against Gram negative and Gram positive bacterial strains viz; (i) Escherichia coli (MTCC 443), (ii) Pseudomonas aeruginosa (MTCC 424) (iii) Staphylococcus aureus (MTCC 96) and (iv) Streptococcus pyogenes (MTCC 442) using agar well diffusion method. Compounds 7g (R = 2-OH, 4-OCHF2), 7h (R = 2-NO2), 7i (R = 3-NO2), 7j (R = 4-NO2) and 7n (4-OH) displayed excellent antibacterial activity (zone of inhibition: 25-32 mm) against both the Gram positive and Gram negative bacterial strains. Compounds 7f (R = 2-F, 3-Cl), 7k (R = 2-OMe), 7l (R = 4-OMe), 7m (R = 4-OEt), 7o (R = 3-OMe), 7p (R = 3,4-OEt) showed good antibacterial activity (zone of inhibition: 19-26 mm).

  本研究描述了从商业可获得的4,5,6,7-四氢噻吩[3,2-c]吡啶（1）合成的3-(6,7-二氢噻吩[3,2-c]吡啶-5(4H)-基磺酰基)苯肼衍生物（7a-p），并研究了其抗菌活性。通过核磁共振（1H NMR）、红外光谱（IR）和质谱分析对合成化合物7a-p进行了表征。这些合成化合物在琼脂孔扩散法下对革兰氏阴性和革兰氏阳性菌株进行了测试，包括：（i）大肠杆菌（MTCC 443）、（ii）铜绿假单胞菌（MTCC 424）、（iii）金黄色葡萄球菌（MTCC 96）和（iv）化脓性链球菌（MTCC 442）。化合物7g（R = 2-OH, 4-OCHF2）、7h（R = 2-NO2）、7i（R = 3-NO2）、7j（R = 4-NO2）和7n（4-OH）对革兰氏阳性和阴性菌株均表现出优异的抗菌活性（抑菌圈直径：25-32毫米）。化合物7f（R = 2-F, 3-Cl）、7k（R = 2-OMe）、7l（R = 4-OMe）、7m（R = 4-OEt）、7o（R = 3-OMe）、7p（R = 3,4-OEt）显示出良好的抗菌活性（抑菌圈直径：19-26毫米）。