Ethyl 4-(4-amino-3-sulfanylphenyl)-4-oxobutanoate | 136912-43-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethyl 4-(4-amino-3-sulfanylphenyl)-4-oxobutanoate
• CAS: 136912-43-1
• 化学式: C₁₂H₁₅NO₃S
• 分子量: 253.322
• InChiKey: YQVMRDWBTHRSPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 4-(4-amino-3-sulfanylphenyl)-4-oxobutanoate 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 72.5h， 生成 ethyl 4-oxo-4-<2-<(3-chlorobenzoyl)oxy>-3,4-dihydro-3-oxo-2H-1,4-benzothiazin-7-yl>butyrate
  参考文献：
  名称：

  Heteroatom analogs of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones

  摘要：

  A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.

  DOI：

  10.1021/jm00079a023
• 作为产物：
  描述：

  4-(4-氨基苯基)-4-氧代丁酸乙酯 在 sodium sulfide 、 溴 作用下， 以 溶剂黄146 为溶剂， 反应 1.25h， 生成 Ethyl 4-(4-amino-3-sulfanylphenyl)-4-oxobutanoate
  参考文献：
  名称：

  Heteroatom analogs of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones

  摘要：

  A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.

  DOI：

  10.1021/jm00079a023

文献信息

• [EN] 1-ARYLSULPHONYL, ARYLCARBONYL AND 1-ARYLPHOSPHONYL-3-PHENYL-1,4,5,6-TETRAHYDROPYRIDAZINES<br/>[FR] 1-ARYLSULFONYLE, ARYLCARBONYLE ET 1-ARYLPHOSPHONYLE-3-PHENYLE-1,4,5,6-TETRAHYDROPYRIDAZINES
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：WO1994001412A1

  公开（公告）日：1994-01-20

  (EN) 1-phenylsulphonyl, 1-phenylcarbonyl, 1-phenylthiocarbonyl and 1-phenylphosphenyl-3-aryl-1,4,5,6-tetrahydropyridazines are disclosed to promote bone cell growth to be progestin antagonists and agonists and to bind to the GABAA receptor.(FR) L'invention concerne des 1-phénylsulfonyle, 1-phénylcarbonyle, 1-phénylthiocarbonyle et 1-phénylphosphonyle-3-aryle-1,4,5,6-tétrahydropyridazines utiles pour stimuler la croissance des cellules osseuses, constituant des antagonistes et des agonistes de la progestérone et pouvant se fixer au récepteur d'acide gamma-aminobutyrique (GABAA).

  1-苯基砜基-1- ary-1,4,5,6-四氢吡咯烷、1-苯基羰基、1-苯基硫=keydcarryl和1-苯基磷酸基-3- ary-1,4,5,6-四氢吡咯烷被发现可以促进骨细胞生长，是雄激素拮抗剂和agonists，并且能结合到谷氨酸钠氨基丁酸 (GABAA) 接受器。
• 1-ARYLSULPHONYL, ARYLCARBONYL AND 1-ARYLPHOSPHONYL-3-PHENYL-1,4,5,6-TETRAHYDROPYRIDAZINES
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：EP0650480A1

  公开（公告）日：1995-05-03
• US5684151A
  申请人：——

  公开号：US5684151A

  公开（公告）日：1997-11-04
• Heteroatom analogs of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones
  作者：Donald W. Combs、Marianne S. Rampulla、James P. Demers、Robert Falotico、John B. Moore

  DOI：10.1021/jm00079a023

  日期：1992.1

  A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.