cis/trans-2-(1-(2,3-dichlorobenzylidene)-acetonyl)-1,3,4-oxadiazol | 103946-24-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: cis/trans-2-(1-(2,3-dichlorobenzylidene)-acetonyl)-1,3,4-oxadiazol
• 英文别名: 1-(2,3-dichlorophenyl)-2-(1,3,4-oxadiazol-2-yl)-but-1-en-3-one；4-(2,3-Dichlorophenyl)-3-(1,3,4-oxadiazol-2-yl)but-3-en-2-one
• CAS: 103946-24-3
• 化学式: C₁₂H₈Cl₂N₂O₂
• 分子量: 283.114
• InChiKey: WRTMMQGUTGEROQ-UHFFFAOYSA-N

物化性质

• 沸点：
  465.9±55.0 °C(Predicted)
• 密度：
  1.420±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cis/trans-2-(1-(2,3-dichlorobenzylidene)-acetonyl)-1,3,4-oxadiazol 在 lithium 作用下， 以 二甲基亚砜 为溶剂， 反应 35.0h， 生成 isopropyl-(R)-1,4-dihydro-2,6-dimethyl-4-(2,3-dichlorophenyl)-5-(1,3,4-oxadiazol-2-yl)-pyridine-3-carboxylate
  参考文献：
  名称：

  Calcium- and calmodulin-antagonism of elnadipine derivatives: comparative SAR

  摘要：

  The Ca2+-antagonistic properties of elnadipine derivatives have been quantified by means of binding experiments in bovine cerebral cortex membranes using H-3-nitrendipine. Competition experiments have shown a 308-fold concentration range of K(i)-values (2.9 x 10(-10) to 8.9 x 10(-8)) for elnadipine derivatives and a eudismic ratio for elnadipine and its (+)-enantiomer of 448. Calmodulin (CaM)-antagonistic properties have been measured in the test system of CaM-stimulated phosphodiesterase. The concentration range of IC50 values only amounts to 9 (5 x 10(-7) to 4.5 x 10(-6) M). In contrast to Ca2+-antagonism, enantioselectivity of CaM-inhibition by elnadipine is negligible. CaM-antagonistic potency of elnadipine derivatives is diminished by a factor of 10 to 5000 as compared to their Ca2+-antagonistic potency. The following conclusions regarding structural determinants of Ca2+- and CaM-antagonistic properties can be made: lipophilic substituents of the oxadiazole in 5-position of the dihydropyridine (DHP) ring increase the CaM-antagonistic and decrease the Ca2+-antagonistic potency: correspondingly the unsubstituted compound is the strongest Ca2+- and the weakest CaM-antagonist; 1,3,4-oxadiazole substitution is superior to 1,2,4-oxadiazole as regards Ca2+- and CaM-antagonistic potency.

  DOI：

  10.1016/0223-5234(92)90006-m
• 作为产物：
  描述：

  2,3-二氯苯甲醛 、 2-Acetonyl-1,3,4-oxadiazole 在 哌啶 作用下， 以 甲苯 为溶剂， 以62%的产率得到cis/trans-2-(1-(2,3-dichlorobenzylidene)-acetonyl)-1,3,4-oxadiazol
  参考文献：
  名称：

  Calcium- and calmodulin-antagonism of elnadipine derivatives: comparative SAR

  摘要：

  The Ca2+-antagonistic properties of elnadipine derivatives have been quantified by means of binding experiments in bovine cerebral cortex membranes using H-3-nitrendipine. Competition experiments have shown a 308-fold concentration range of K(i)-values (2.9 x 10(-10) to 8.9 x 10(-8)) for elnadipine derivatives and a eudismic ratio for elnadipine and its (+)-enantiomer of 448. Calmodulin (CaM)-antagonistic properties have been measured in the test system of CaM-stimulated phosphodiesterase. The concentration range of IC50 values only amounts to 9 (5 x 10(-7) to 4.5 x 10(-6) M). In contrast to Ca2+-antagonism, enantioselectivity of CaM-inhibition by elnadipine is negligible. CaM-antagonistic potency of elnadipine derivatives is diminished by a factor of 10 to 5000 as compared to their Ca2+-antagonistic potency. The following conclusions regarding structural determinants of Ca2+- and CaM-antagonistic properties can be made: lipophilic substituents of the oxadiazole in 5-position of the dihydropyridine (DHP) ring increase the CaM-antagonistic and decrease the Ca2+-antagonistic potency: correspondingly the unsubstituted compound is the strongest Ca2+- and the weakest CaM-antagonist; 1,3,4-oxadiazole substitution is superior to 1,2,4-oxadiazole as regards Ca2+- and CaM-antagonistic potency.

  DOI：

  10.1016/0223-5234(92)90006-m

文献信息

• Dihydro-2,6-dimethyl pyridines, formulations and method of use for
  申请人：Cassella Aktiengesellschaft

  公开号：US04681891A1

  公开（公告）日：1987-07-21

  1,4-dihydropyridines of the formula I ##STR1## wherein R.sup.1 denotes optionally substituted phenyl, pyridyl or thienyl, R.sup.2 denotes optionally substituted oxadiazolyl, thiadiazolyl or thiazolyl and R.sup.3 denotes hydrogen or --COOH, their preparation by a modified Hantzsch synthesis and their use as a calcium-agonist in pharmacy.

  公式I中的1,4-二氢吡啶化合物 ##STR1## 其中R.sup.1表示可选取代的苯基、吡啶基或噻吩基，R.sup.2表示可选取代的噁二唑基、噻二唑基或噻唑基，R.sup.3表示氢或--COOH，它们通过改良的Hantzsch合成法制备，并用作药学中的钙激动剂。
• Calcium- and calmodulin-antagonism of elnadipine derivatives: comparative SAR
  作者：R Mannhold、B Jablonka、W Voigt、K Schönafinger、E Schraven

  DOI：10.1016/0223-5234(92)90006-m

  日期：1992.4

  The Ca2+-antagonistic properties of elnadipine derivatives have been quantified by means of binding experiments in bovine cerebral cortex membranes using H-3-nitrendipine. Competition experiments have shown a 308-fold concentration range of K(i)-values (2.9 x 10(-10) to 8.9 x 10(-8)) for elnadipine derivatives and a eudismic ratio for elnadipine and its (+)-enantiomer of 448. Calmodulin (CaM)-antagonistic properties have been measured in the test system of CaM-stimulated phosphodiesterase. The concentration range of IC50 values only amounts to 9 (5 x 10(-7) to 4.5 x 10(-6) M). In contrast to Ca2+-antagonism, enantioselectivity of CaM-inhibition by elnadipine is negligible. CaM-antagonistic potency of elnadipine derivatives is diminished by a factor of 10 to 5000 as compared to their Ca2+-antagonistic potency. The following conclusions regarding structural determinants of Ca2+- and CaM-antagonistic properties can be made: lipophilic substituents of the oxadiazole in 5-position of the dihydropyridine (DHP) ring increase the CaM-antagonistic and decrease the Ca2+-antagonistic potency: correspondingly the unsubstituted compound is the strongest Ca2+- and the weakest CaM-antagonist; 1,3,4-oxadiazole substitution is superior to 1,2,4-oxadiazole as regards Ca2+- and CaM-antagonistic potency.