cis-7-amino-5,6-dihydro-6-hydroxy-5,5-dimethyl-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: cis-7-amino-5,6-dihydro-6-hydroxy-5,5-dimethyl-5H-thieno<3,2-b>pyran
• 英文别名: (6R,7S)-7-amino-5,5-dimethyl-6,7-dihydrothieno[3,2-b]pyran-6-ol
• 化学式: C₉H₁₃NO₂S
• 分子量: 199.274
• InChiKey: XKGVOPVKKXUCIE-HTRCEHHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  83.7
• 氢给体数：
  2
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	5,6-dihydro-7-hydroxy-5,5-dimethyl-5H-thieno<3,2-b>pyran	129969-31-9	C9H12O2S	184.259
  ——	5.6-Dihydro-5,5-dimethyl-7H-thieno[3,2-b]pyran-7-one	129969-30-8	C9H10O2S	182.243

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C14H19NO3S	281.376
  ——	(-)-trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C14H19NO3S	281.376
  ——	trans-2-bromo-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C14H18BrNO3S	360.272
  ——	trans-2-cyano-5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C15H18N2O3S	306.386
  ——	(-)-trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C14H18N2O5S	326.373
  ——	trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C14H18N2O5S	326.373
  ——	((S)-1-Phenyl-ethyl)-carbamic acid (6S,7S)-5,5-dimethyl-7-(2-oxo-piperidin-1-yl)-6,7-dihydro-5H-thieno[3,2-b]pyran-6-yl ester	143164-06-1	C23H28N2O4S	428.552
  ——	trans-6-(benzyloxy)-2-bromo-5,6-dihydro-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C21H24BrNO3S	450.396
  ——	trans-6-(benzyloxy)-2-cyano-5,6-dihydro-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C22H24N2O3S	396.51
  ——	trans-6-(benzyloxy)-2-carbamoyl-5,6-dihydro-5,5-dimethyl-7-(2-oxopiperidin-1-yl)-5H-thieno<3,2-b>pyran	——	C22H26N2O4S	414.525

反应信息

• 作为反应物：
  描述：

  cis-7-amino-5,6-dihydro-6-hydroxy-5,5-dimethyl-5H-thieno<3,2-b>pyran 在 N,N-二甲基乙醇胺 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 44.0h， 生成 ((S)-1-Phenyl-ethyl)-carbamic acid (6S,7S)-5,5-dimethyl-7-(2-oxo-piperidin-1-yl)-6,7-dihydro-5H-thieno[3,2-b]pyran-6-yl ester
  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：

  5.6-Dihydro-5,5-dimethyl-7H-thieno[3,2-b]pyran-7-one 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 sodium azide 、 molecular sieve 、 水 、 sodium hydride 、 对甲苯磺酸 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 54.0h， 生成 cis-7-amino-5,6-dihydro-6-hydroxy-5,5-dimethyl-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

• 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.