trans-6-(benzyloxy)-2-bromo-5,6-dihydro-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-6-(benzyloxy)-2-bromo-5,6-dihydro-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran
• 英文别名: trans-6-Benzyloxy-2-bromo-5,6-dihydro-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-7H-thieno[3,2-b]pyran；1-[(6S,7S)-2-bromo-5,5-dimethyl-6-phenylmethoxy-6,7-dihydrothieno[3,2-b]pyran-7-yl]piperidin-2-one
• 化学式: C₂₁H₂₄BrNO₃S
• 分子量: 450.396
• InChiKey: HZTCCTQHKSUGHL-QUCCMNQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  67
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-6-(benzyloxy)-2-bromo-5,6-dihydro-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran 在 ammonium hydroxide 、 bis(triphenylphosphine)palladium(II)-chloride 、 三乙胺 作用下， 以 甲醇 为溶剂， 25.0~100.0 ℃ 、1.1 MPa 条件下， 反应 216.0h， 生成 trans-6-(benzyloxy)-2-carbamoyl-5,6-dihydro-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 溴 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 trans-6-(benzyloxy)-2-bromo-5,6-dihydro-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：US05284857A1

  公开（公告）日：1994-02-08

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

  本发明揭示了替代噻吩并制备噻吩并的过程。这些噻吩并可用作降压药物；抗心绞痛药和外周抗血管收缩药。
• US5284857A
  申请人：——

  公开号：US5284857A

  公开（公告）日：1994-02-08
• US5378713A
  申请人：——

  公开号：US5378713A

  公开（公告）日：1995-01-03
• 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.