[Synthesis and vasorelaxant activities of benzopyran-4-one hydrazone derivatives].
OBJECTIVE
In search of more potent, less toxic and selective potassium channel openers.


METHODS
According to the structure-activity relationships of benzopyran compounds and the features of structures of aprikalim, dofetilide and nifekalant, twenty benzopyran-4-one hydrazone derivatives have been designed and synthesized from 4-cyanophenos through acetylation, Fries rearrangment, cyclization, hydrazone, substitution reaction and so on. The compounds were tested for their vasorelaxant activity in low (30 mmol.L-1) and high (80 mmol.L-1) KCl-induced contraction of rat aorta to identify potential potassium channel openers in vitro.


RESULTS
Three series of twenty benzopyran-4-one hydrazone derivatives, nominated N-aminoacetyl-(6-cyano-3,4-dihydrospiro [2H-1-benzopyran-2,1'-cyclohexane]-4)-one hydrazone (I), 2-(6-cyano-3, 4-dihydro-2H-1-benzopyran-4-ylene) hydrazinethiocarboxamide derivatives (II) and N-(2-arylethyl) aminoacetyl-(6-cyano-3,4-dihydro-2H-1-benzopyran)-4-one hydrazone (III), have been synthesized. They (I1-9, II1-4 and III1-7) are new compounds. Their chemical structures were determined by IR, 1HNMR, MS and elemental analysis. The vasorelaxant effects of those novel compounds indicated that some of the compounds have vasorelaxant activities at 1 x 10(-6) mol.L-1.


CONCLUSIONS
The vasorelaxant activities of compounds I9, III2 and III5 in inhibiting low KCl-induced vasocontraction at 1 x 10(-6) mol.L-1 are less potent than the reference compound emakalim. However they are more potent than emakalim to inhibition high concentration KCl-induced vasocontraction at 1 x 10(-5) mol.L-1. It is worthy of further study.
Zhao
Sheng-yin
SY
New Drug Research Center, China Pharmaceutical University, Nanjing 210009, China.
Huang
Wen-long
WL
Zhang
Hui-bin
HB
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D014665:Vasodilator Agents