1-Naphthalen-2-ylsulfonylpyrrolidine-3-carboxylic acid | 1394241-84-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-Naphthalen-2-ylsulfonylpyrrolidine-3-carboxylic acid
• CAS: 1394241-84-9
• 化学式: C₁₅H₁₅NO₄S
• 分子量: 305.354
• InChiKey: PSGCTJNLVUTDIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  吡咯烷-3-甲酸 、 2-萘磺酰氯 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 以42%的产率得到1-Naphthalen-2-ylsulfonylpyrrolidine-3-carboxylic 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

• Aldehyde derivatives and their use as calpain inhibitors
  申请人：FUJIREBIO Inc.

  公开号：EP0520336A2

  公开（公告）日：1992-12-30

  Aldehyde derivatives with a specific calpain inhibiting activity and a platelet-aggregation inhibiting effect with formula (I) or formula (II): wherein R1 represents an aromatic hydrocarbon group, a heterocyclic group, or a group of -X-R3 in which X represents O, -S(O)m- (m = 0, 1, or 2), and R3 represents an aromatic hydrocarbon group, a heterocyclic group, or an alkyl group; Z represents R4-Y- or R60-CH(R5)- in which Y represents a 3- to 7-membered nitrogen-containing saturated heterocyclic group, or a single cyclic saturated hydrocarbon group, R4 represents an alkyl group, an alkenyl group, an alkynyl group, an acyl group, a sulfonyl group, an alkoxycarbonyl group, a carbamoyl group, or a thiocarbamoyl group, R5 represents hydrogen, an alkyl group, or an aromatic hydrocarbon group, and R6 represents an acyl group, a carbamoyl group, a thiocarbamoyl group, or an alkyl group; and n is an integer of 1 to 5. wherein R7, R8, R9, and R10 are defined in the specification.

  具有特异性钙蛋白酶抑制活性和血小板聚集抑制作用的式 (I) 或式 (II) 醛衍生物： 其中 R1 代表芳香烃基团、杂环基团或-X-R3 的基团，其中 X 代表 O、-S(O)m- (m = 0、1 或 2)，R3 代表芳香烃基团、杂环基团或烷基；Z 代表 R4-Y- 或 R60-CH(R5)-，其中 Y 代表 3 至 7 元含氮饱和杂环基团，或单环饱和烃基团，R4 代表烷基、烯基、炔基、酰基、磺酰基、烷基、炔基或烷基R5 代表氢、烷基或芳香烃基，R6 代表酰基、氨基甲酰基、硫代氨基甲酰基或烷基；n 是 1 至 5 的整数。 其中 R7、R8、R9 和 R10 的定义见说明书。