1-(2-anthrylsulfonyl)-3-piperidinecarboxylic acid | 1394241-91-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 1-(2-anthrylsulfonyl)-3-piperidinecarboxylic acid
• 英文别名: 1-Anthracen-2-ylsulfonylpiperidine-3-carboxylic acid；1-anthracen-2-ylsulfonylpiperidine-3-carboxylic acid
• CAS: 1394241-91-8
• 化学式: C₂₀H₁₉NO₄S
• 分子量: 369.441
• InChiKey: NVUYTSUMYCCEEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-蒽磺酰氯 、 3-哌啶甲酸 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 以41%的产率得到1-(2-anthrylsulfonyl)-3-piperidinecarboxylic 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

• HTRA INHIBITORS AND CAGA INHIBITORS AND USE THEREOF
  申请人：Psomagen, Inc.

  公开号：EP3906226A1

  公开（公告）日：2021-11-10
• [EN] HTRA INHIBITORS AND CAGA INHIBITORS AND USE THEREOF<br/>[FR] INHIBITEURS DE HTRA ET INHIBITEURS DE CAGA ET LEUR UTILISATION
  申请人：PSOMAGEN INC

  公开号：WO2020142764A1

  公开（公告）日：2020-07-09

  The present application relates to new HtrA inhibitors and use thereof. Additionally, the present application also relates to new peptides for inhibiting CagA and use thereof.
• 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.