New substituted 1,4-benzoxazine derivatives with potential intracellular calcium activity.
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.
Institut de Chimie Organique et Analytique associé au CNRS, Université d'Orléans, BP 6759, 45067 Orléans Cedex 2, France.
A S
AS
Bourlot
I
I
Sánchez
G
G
Dureng
G
G
Guillaumet
R
R
Massingham
A
A
Monteil
E
E
Winslow
M D
MD
Pujol
J Y
JY
Mérour
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D010078:Oxazines; D010656:Phenylephrine; D002118:Calcium