2-(3,3-diethylthioureido)-5,6-dihydro-4H-cyclohepta[4,5]thiophene-3-carboxylic acid | 257611-14-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环七噻吩
• 英文名称: 2-(3,3-diethylthioureido)-5,6-dihydro-4H-cyclohepta[4,5]thiophene-3-carboxylic acid
• 英文别名: 2-(3,3-diethylthioureido)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid；2-(diethylcarbamothioylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid
• CAS: 257611-14-6
• 化学式: C₁₅H₂₂N₂O₂S₂
• 分子量: 326.484
• InChiKey: YGHVDTHISFMMCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  113
• 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
  ——	ethyl 2-(3,3-diethylthioureido)-5,6,7,8-tetrahydro-4H-cyclohepta[4,5]thiophene-3-carboxylate	257610-99-4	C17H26N2O2S2	354.538
  2-氨基环庚烷并[B]噻吩-3-羧酸乙酯	2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid ethyl ester	40106-13-6	C12H17NO2S	239.338
  ——	ethyl 2-(isothiocyanato)-5,6,7,8-tetrahydro-4H-cyclohepta[4,5]thiophene-3-carboxylate	257610-91-6	C13H15NO2S2	281.4

反应信息

• 作为反应物：
  描述：

  2-(3,3-diethylthioureido)-5,6-dihydro-4H-cyclohepta[4,5]thiophene-3-carboxylic acid 在 mercury(II) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以78%的产率得到2-Diethylamino-6,7,8,9-tetrahydro-5H-3-oxa-10-thia-1-aza-benzo[a]azulen-4-one
  参考文献：
  名称：

  2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.

  DOI：

  10.1021/jm991108w
• 作为产物：
  描述：

  ethyl 2-(3,3-diethylthioureido)-5,6,7,8-tetrahydro-4H-cyclohepta[4,5]thiophene-3-carboxylate 在 sodium hydroxide 、 硫酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 74.83h， 生成 2-(3,3-diethylthioureido)-5,6-dihydro-4H-cyclohepta[4,5]thiophene-3-carboxylic acid
  参考文献：
  名称：

  2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.

  DOI：

  10.1021/jm991108w

文献信息

• Aromatic 2-(Thio)ureidocarboxylic Acids As a New Family of Modulators of Multidrug Resistance-Associated Protein 1: Synthesis, Biological Evaluation, and Structure−Activity Relationships
  作者：Hans-Georg Häcker、Stefan Leyers、Jeanette Wiendlocha、Michael Gütschow、Michael Wiese

  DOI：10.1021/jm900688v

  日期：2009.8.13

  Four series of aromatic carboxylic acids were prepared with a urea or thiourea moiety at the neighboring position to the carboxyl group and benzene or thiophene as aromatic scaffold. Using a calcein AM assay, these compounds were evaluated as inhibitors of multidrug resistance-associated protein I (MRP1) and selected compounds were examined toward P-glycoprotein (P-gp) as well as breast cancer resistance protein (BCRP) to assess selectivity for MRP1. Two 2-thioureidobenzo[b]-thiophene-3-carboxylic acids (48, 49) were identified as particularly potent inhibitors of MRP1, with IC50 values of around 1 mu M. The structural features of this new family or nontoxic MRP1 inhibitors include a (thio)urea disubstituted with preferentially two alkyl groups at the terminal nitrogen and an additional fused aromatic ring.
• 2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase
  作者：Michael Gütschow、Lars Kuerschner、Ulf Neumann、Markus Pietsch、Reik Löser、Norman Koglin、Kurt Eger

  DOI：10.1021/jm991108w

  日期：1999.12.1

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.