New substituted 1,4-benzoxazine derivatives with potential intracellular calcium activity

被引:85
作者
Bourlot, AS
Sánchez, I
Dureng, G
Guillaumet, G
Massingham, R
Monteil, A
Winslow, E
Pujol, MD
Mérour, JY
机构
[1] Univ Barcelona, Fac Farm Quim Farmaceut, E-08028 Barcelona, Spain
[2] Univ Orleans, CNRS, Inst Chim Organ & Analyt, F-45067 Orleans 2, France
[3] RL CERM, ZI La Varenne, F-63203 Riom, France
关键词
D O I
10.1021/jm970795t
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed. The 4-benzyl-3,4-dihydro-2[3-[[2-(3,4-dimethoxyphenyl)ethyl]amino]propyl]-2H-1,4-benzoxazine (3c) is the most potent derivative of the series with a ratio of IC50 values against PE (phenylephrine) and K+ of 2.1. Under these test conditions a ratio near 1 indicates potential intracellular calcium activity while a ratio greater than 100 an action on extracellular calcium influx.
引用
收藏
页码:3142 / 3158
页数:17
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