PT  - JOURNAL ARTICLE
AU  - Shinichi Fukuyama
AU  - Yoshimi Hirasawa
AU  - Yasuko Kato
AU  - Mie Nishio
AU  - Mitsuko Ohno
AU  - Shigetaka Nishino
AU  - Kazuhiro Maeda
AU  - Masayuki Kato
AU  - Yasuhiro Kita
TI  - Structure-Activity Relationships of Spontaneous Nitric Oxide Releasers, FK409 and its Derivatives
DP  - 1997 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 236--242
VI  - 282
IP  - 1
4099  - http://jpet.aspetjournals.org/content/282/1/236.short
4100  - http://jpet.aspetjournals.org/content/282/1/236.full
SO  - J Pharmacol Exp Ther1997 Jul 01; 282
AB  - (±)-(E)-4-Ethyl-2-[(E)-hydroxyimino] - 5 - nitro-3-hexenamide (FK409) shows both potent in vitro vasorelaxant and antiplatelet activities via nitric oxide (NO) generated spontaneously from the compound. In this study, we measured spontaneous NO-releasing rates of a series of FK409 derivatives, of which chain lengths or substituents were systematically modified, in sodium-phosphate buffer solution at pH 7.4. Furthermore, we studied their in vitro antiplatelet and vasorelaxant effects to evaluate relationships between spontaneous NO-releasing activities of FK409 analogs and their biological activities. FK409 derivatives were found to possess different spontaneous NO-releasing rates and biological activities according to their structural modification. In addition, these studies revealed a close correlation between NO-releasing rates of FK409 derivatives and their in vitro antiplatelet activities in human platelet-rich plasma, whereas the in vitro vasorelaxant activities of these compounds in isolated rat aorta did not correlate with the rates of NO liberation. The vasorelaxant effects were supposed to be affected by the structural properties of FK409 derivatives as well as their NO-releasing abilities. The American Society for Pharmacology and Experimental Therapeutics