trans-5,6-dihydro-6-hydroxy-2,5,5-trimethyl-7-(2-oxopyrrolidin-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-2,5,5-trimethyl-7-(2-oxopyrrolidin-1-yl)-5H-thieno<3,2-b>pyran
• 英文别名: trans-5,6-dihydro-6-hydroxy-2,5,5-trimethyl-7-(2-oxopyrrolidin-1-yl)-5H-thieno[3,2-b]pyran；1-[(6S,7S)-6-hydroxy-2,5,5-trimethyl-6,7-dihydrothieno[3,2-b]pyran-7-yl]pyrrolidin-2-one
• 化学式: C₁₄H₁₉NO₃S
• 分子量: 281.376
• InChiKey: CYNHPLXCFGPEPS-YPMHNXCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 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

• 作为产物：
  描述：

  5.6-Dihydro-5,5-dimethyl-7H-thieno[3,2-b]pyran-7-one 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 molecular sieve 、 trans-benzyl(chloro)-bis(triphenylphosphine)palladium(II) 、 水 、 溴 、 sodium hydride 、 对甲苯磺酸 作用下， 以 六甲基磷酰三胺 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 135.5h， 生成 trans-5,6-dihydro-6-hydroxy-2,5,5-trimethyl-7-(2-oxopyrrolidin-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