trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡喃类
• 英文名称: trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran
• 英文别名: cis-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran；1-[(6R,7R)-6-hydroxy-5,5-dimethyl-6,7-dihydrothieno[3,2-b]pyran-7-yl]piperidin-2-one
• 化学式: C₁₄H₁₉NO₃S
• 分子量: 281.376
• InChiKey: GETRHWLSLKKRAJ-WCQYABFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以78%的产率得到trans-2-bromo-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran
  参考文献：
  名称：

  Thiophene systems. 14. Synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxythieno[3,2-b]pyrans and related compounds as new potassium channel activators

  摘要：

  The synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxy-5,5-di-methylthieno[3,2-b]pyrans and related compounds are described. The compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats (SHR) and selected compounds were evaluated in vitro for increases in Rb-86 efflux in rabbit isolated mesenteric arteries. The effects on activity in SHR of lactam ring size, the presence of heteroatoms in the lactam ring, the relative stereochemistry at C-6 and C-7, and the substituents on the thiophene ring are examined. The best racemic compound in this series is 32, trans-5,6-dihydro-6-hydroxy-5,5-di-methyl-2-nitro-7-(2-oxopiperidin-1-yl)-5H-thieno[3,2-b]pyran, which is 10-fold more potent than cromakalim with an ED30 = 0.015 mg/kg in SHR. Compound 32 could be resolved and the antihypertensive activity determined to reside primarily in the (6S,7S)-(-)-enantiomer 41. Surprisingly, the elimination of water to give the enamides 50-52, thiophene isosteres of bimakalim, diminishes activity significantly.

  DOI：

  10.1021/jm00101a020
• 作为产物：
  描述：

  5-氯代戊酰氯 在 N,N-二甲基乙醇胺 、 sodium ethanolate 、 sodium hydride 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 44.5h， 生成 trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran
  参考文献：
  名称：

  Thiophene systems. 14. Synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxythieno[3,2-b]pyrans and related compounds as new potassium channel activators

  摘要：

  The synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxy-5,5-di-methylthieno[3,2-b]pyrans and related compounds are described. The compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats (SHR) and selected compounds were evaluated in vitro for increases in Rb-86 efflux in rabbit isolated mesenteric arteries. The effects on activity in SHR of lactam ring size, the presence of heteroatoms in the lactam ring, the relative stereochemistry at C-6 and C-7, and the substituents on the thiophene ring are examined. The best racemic compound in this series is 32, trans-5,6-dihydro-6-hydroxy-5,5-di-methyl-2-nitro-7-(2-oxopiperidin-1-yl)-5H-thieno[3,2-b]pyran, which is 10-fold more potent than cromakalim with an ED30 = 0.015 mg/kg in SHR. Compound 32 could be resolved and the antihypertensive activity determined to reside primarily in the (6S,7S)-(-)-enantiomer 41. Surprisingly, the elimination of water to give the enamides 50-52, thiophene isosteres of bimakalim, diminishes activity significantly.

  DOI：

  10.1021/jm00101a020

文献信息

• Substituted thienopyrans as antihypertensive agents
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：EP0360621A1

  公开（公告）日：1990-03-28

  Substituted thienopyrans and processes for preparing the thienopyrans are disclosed. The thienopyrans are useful as antihypertensive agents; antianginals are peripheral antivasoconstrictive agents.

  本研究公开了取代的噻吩并吡喃和制备噻吩并吡喃的工艺。噻吩并吡喃类化合物可用作降压药；拮抗剂是外周抗血管收缩药。
• Thiophene systems. 14. Synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxythieno[3,2-b]pyrans and related compounds as new potassium channel activators
  作者：Pauline J. Sanfilippo、James J. McNally、Jeffery B. Press、Louis J. Fitzpatrick、Maud J. Urbanski、Laurence B. Katz、Edward Giardino、Robert Falotico、Joseph Salata

  DOI：10.1021/jm00101a020

  日期：1992.11

  The synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxy-5,5-di-methylthieno[3,2-b]pyrans and related compounds are described. The compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats (SHR) and selected compounds were evaluated in vitro for increases in Rb-86 efflux in rabbit isolated mesenteric arteries. The effects on activity in SHR of lactam ring size, the presence of heteroatoms in the lactam ring, the relative stereochemistry at C-6 and C-7, and the substituents on the thiophene ring are examined. The best racemic compound in this series is 32, trans-5,6-dihydro-6-hydroxy-5,5-di-methyl-2-nitro-7-(2-oxopiperidin-1-yl)-5H-thieno[3,2-b]pyran, which is 10-fold more potent than cromakalim with an ED30 = 0.015 mg/kg in SHR. Compound 32 could be resolved and the antihypertensive activity determined to reside primarily in the (6S,7S)-(-)-enantiomer 41. Surprisingly, the elimination of water to give the enamides 50-52, thiophene isosteres of bimakalim, diminishes activity significantly.