117574-76-2Relevant articles and documents
Dual Inhibitors of Thromboxane A2 Synthase and 5-Lipoxygenase with Scavenging Activity of Active Oxygen Species. Synthesis of a Novel Series of (3-Pyridylmethyl)benzoquinone Derivatives
Ohkawa, Shigenori,Terao, Shinji,Terashita, Zen-ichi,Shibouta, Yumiko,Nishikawa, Kohei
, p. 267 - 276 (2007/10/02)
A novel series of (3-pyridylmethyl)benzoquinone derivatives was molecular designed and synthesized for the dual purpose of inhibiting thromboxane A2 and leukotriene biosynthesis enzymes and scavenging active oxygen species (AOS).They were evaluated for inhibition of TXA2 synthase, inhibition of 5-lipoxygenase, and for their scavenging activity of AOS using the thiobarbituric acid method. 2,3,5-Trimethyl-6-(3-pyridylmethyl)-1,4-benzoquinone (24, CV-6504) was the most promising derivative since it showed efficient AOS scavenging activity (inhibition of lipid peroxidation in rat brain homogenates: IC50 = 1.8 10-6 M) as well as potent, specific, and well-balanced inhibitory effects on both enzymes (inhibitory effect on TXA2 synthase in human blood, IC50 = 3.3 10-7 M; inhibitory effect on 5-lipoxygenase in human blood, IC50 = 3.6 10-7 M).In adriamycin-induced proteinuria in a rat model, compound 24 at 10 mg/kg per day (po) suppressed proteinuria by more than 50percent.The proteinuria, however, could not be reduced by single administration of an inhibitor specific for thromboxane A2 synthase or for 5-lipoxygenase .The proteinuria was also not reduced by administration of an AOS scavenger, 2-O-octadecylascorbic acid (4, CV-3611).Triple function compounds such as compound 24 that specifically inhibit both enzymes as well as scavenge AOS possess a variety of pharmacologically beneficial effects.
Certain benzoquinones, naphthoquinones, corresponding hydroquinones which exhibit thromboxane A2 synthetase inhibition or receptor antagonism and the like
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, (2008/06/13)
Quinone derivatives represented by the general formula STR1 (wherein, R1 and R2, the same or different, refer to a hydrogen atom, methyl or methoxymethyl group, or R1 and R2 bind together to form --CH=CH--CH=CH--; R3 is a hydrogen atom or methyl group; R4 is a nitrogen-containing heterocyclic group which may be substituted; R5 is a hydrogen atom, methyl group, hydroxymethyl group which may be substituted, or a carboxyl group which may be esterified or amidated; Z is STR2 (wherein, R' is hydrogen atom or methyl group); n is an integer from 0 through 12, m is an integer from 0 through 3, and k is an integer from 0 through 7, providing that, when m is 2 or 3, Z and k are able to vary appropriately in the repeating unit shown in [ ]), and the hydroquinone derivatives thereof, are novel compounds, possess improvement effects of metabolism of polyunsaturated fatty acids, particularly two or more of inhibition of production of fatty acid peroxides, inhibition of production of metabolites in 5-lipoxygenase pathway, inhibition of thromboxane A2 synthetase, thromboxane A2 receptor antagonism and scavenging action of active oxygen species, and of use as drugs, such as antithrombotics, anti-vascular constriction agents, anti-asthma agent, antiallergic agents, therapeutics for psoriasis, agents for improvement in heart, brain and cardiovascular systems, therapeutics for nephritis, active oxygen-eliminating agents, anticancer agents, agents for improvement of control of arachidonate cascade products, etc.
