ethyl 3-(methanesulfonylamino)isoxazole-5-carboxylate | 933055-57-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-(methanesulfonylamino)isoxazole-5-carboxylate
• CAS: 933055-57-3
• 化学式: C₇H₁₀N₂O₅S
• 分子量: 234.233
• InChiKey: KRLKZRRRUYCUSF-UHFFFAOYSA-N

物化性质

• 熔点：
  99-101 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  398.6±52.0 °C(Predicted)
• 密度：
  1.460±0.06 g/cm3(Predicted)

反应信息

• 作为反应物：
  描述：

  ethyl 3-(methanesulfonylamino)isoxazole-5-carboxylate 在 sodium tetrahydroborate 、 Trimethylphenylammonium tribromide 、 二甲羟胺盐酸盐 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 N-[5-(2-bromo-1-hydroxyethyl)isoxazol-3-yl]methanesulfonamide
  参考文献：
  名称：

  Novel chiral isoxazole derivatives: Synthesis and pharmacological characterization at human β-adrenergic receptor subtypes

  摘要：

  Isoxazole derivative (+/-)-4 and the three pairs of stereoisomeric 3-bromo-isoxazolyl amino alcohols (S,R)-(-)-7a/(R,R)(+)-7b, (S, R)-(-)-8a/(R, R)-(+)-8b, and (S, R)-(-)-9a/(R, R)-(+)-9b were synthesized and assayed for their affinity and efficacy at human beta(1)-, beta(2)-, and beta(3)-adrenergic receptors (beta-ARs) in membranes from Chinese hamster ovary (CHO) cells stably transfected with the respective receptor subtype. Whereas derivative ()-4 did not bind at all three P-ARs, stereoisomers (S, R)-7a-(S, R)-9a behaved as high-affinity ligands at beta(1)- and, particularly, at beta(2)-ARs (K-i 2.82-66.7 nM). The Ki values of isomers (R,R)-7b-(R,R)-9b at beta(1)- and beta(2)-subtypes were about 30-100 times higher than those of their (S, R)-7a-9a counterparts, indicating a sizable stereochemical effect. The affinity at beta(3)-ARs was negligible for all the investigated compounds. When submitted to a functional assay, the three stereoisomeric pairs showed a comparable pattern of efficacy at all three beta-AR subtypes. The highest value of efficacy (75-90%) was observed at beta(2)-ARs, whereas all compounds behaved as partial agonists (30-60%) at the beta(3)-subtype. The lowest degree of efficacy (15-35%) was found at beta(1)-ARs. The affinity/efficacy profile of the derivatives under study has been compared with that of the two model compounds, Broxaterol [(+/-)-1] and BRL 37344 [(+/-)-6]. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.056
• 作为产物：
  描述：

  3-氨基异恶唑-5-羧酸乙酯 、 甲基磺酰氯 在 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 1.0h， 以81%的产率得到ethyl 3-(methanesulfonylamino)isoxazole-5-carboxylate
  参考文献：
  名称：

  Novel chiral isoxazole derivatives: Synthesis and pharmacological characterization at human β-adrenergic receptor subtypes

  摘要：

  Isoxazole derivative (+/-)-4 and the three pairs of stereoisomeric 3-bromo-isoxazolyl amino alcohols (S,R)-(-)-7a/(R,R)(+)-7b, (S, R)-(-)-8a/(R, R)-(+)-8b, and (S, R)-(-)-9a/(R, R)-(+)-9b were synthesized and assayed for their affinity and efficacy at human beta(1)-, beta(2)-, and beta(3)-adrenergic receptors (beta-ARs) in membranes from Chinese hamster ovary (CHO) cells stably transfected with the respective receptor subtype. Whereas derivative ()-4 did not bind at all three P-ARs, stereoisomers (S, R)-7a-(S, R)-9a behaved as high-affinity ligands at beta(1)- and, particularly, at beta(2)-ARs (K-i 2.82-66.7 nM). The Ki values of isomers (R,R)-7b-(R,R)-9b at beta(1)- and beta(2)-subtypes were about 30-100 times higher than those of their (S, R)-7a-9a counterparts, indicating a sizable stereochemical effect. The affinity at beta(3)-ARs was negligible for all the investigated compounds. When submitted to a functional assay, the three stereoisomeric pairs showed a comparable pattern of efficacy at all three beta-AR subtypes. The highest value of efficacy (75-90%) was observed at beta(2)-ARs, whereas all compounds behaved as partial agonists (30-60%) at the beta(3)-subtype. The lowest degree of efficacy (15-35%) was found at beta(1)-ARs. The affinity/efficacy profile of the derivatives under study has been compared with that of the two model compounds, Broxaterol [(+/-)-1] and BRL 37344 [(+/-)-6]. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.056