6-carbamoyl-2-(diethylamino)-5-methyl-4H-thieno[3,2-d][1,3]thiazin-4-one | 257611-05-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并噻嗪类
• 英文名称: 6-carbamoyl-2-(diethylamino)-5-methyl-4H-thieno[3,2-d][1,3]thiazin-4-one
• 英文别名: 2-(diethylamino)-5-methyl-4-oxo-4H-thieno[2,3-d][1,3]thiazine-6-carboxamide；2-(Diethylamino)-5-methyl-4-oxothieno[2,3-d][1,3]thiazine-6-carboxamide
• CAS: 257611-05-5
• 化学式: C₁₂H₁₅N₃O₂S₂
• 分子量: 297.402
• InChiKey: HVBPTHUTXHAJHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-carbamoyl-2-(diethylamino)-5-methyl-4H-thieno[3,2-d][1,3]thiazin-4-one 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.08h， 生成 5-carbamoyl-2-(3,3-diethylthioureido)-4-methylthiophene-3-carboxylic acid
  参考文献：
  名称：

  Aromatic 2-(Thio)ureidocarboxylic Acids As a New Family of Modulators of Multidrug Resistance-Associated Protein 1: Synthesis, Biological Evaluation, and Structure−Activity Relationships

  摘要：

  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.

  DOI：

  10.1021/jm900688v
• 作为产物：
  描述：

  2-氨在-5-氨基羰基-4-甲基-3-噻吩羧酸乙酯 在 硫酸 、 calcium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 128.0h， 生成 6-carbamoyl-2-(diethylamino)-5-methyl-4H-thieno[3,2-d][1,3]thiazin-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