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Chemical Compound Review:

SureCN6581572 3-(4-methylsulfinylphenyl)-2- pyridin-4-yl...

Synonyms: Skf-105809, SKF 105809, AC1L2W3W, 122454-69-7

Marshall, P.J. et al., Olivera, D.L. et al., Shohami, E. et al., Griswold, D.E. et al., Reddy, M.P. et al., et al.

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Disease relevance of Skf-105809

The anti-inflammatory activity of SK&F 105809 and its metabolite were evaluated in an antigen-specific murine model of delayed type hypersensitivity (DTH) response, where they were found to affect only the inflammatory and not the induction phase of this response [1].
SK&F 105809 treated rats which received 30 mg/kg had significantly less brain edema, as measured by both gravimetry and water content, at 4 h after trauma [2].
SK&F 105809, a dual inhibitor of 5-LO/CO, significantly reduced hyperalgesia [3].
The present study was designed to determine the effect of a novel drug, SK&F 105809, a dual inhibitor of 5-LO and CO on cerebral edema formation after head injury in rats [2].

High impact information on Skf-105809

The impact of inhibition of both 5-lipoxygenase (5-LO) and CO was seen with platelet-activating factor-induced vascular permeability which was inhibited markedly by SK&F 105809 [4].
In spite of a short half-life (14-18 min) for both SK&F 105809 and the active metabolite SK&F 105561 [2-(4- methylthiophenyl)-3-(4-pyridyl)-6,7-dihydro-[5H]-pyrrolo[1,2-a] imidazole], the pharmacological activity lasted at least 1.5 hr [4].
Neither SK&F 105561 nor SK&F 105809 inhibited the stimulated-turnover of arachidonic acid-containing phospholipids in human monocytes or the activity of cell-free phospholipases A2 and C. Moreover, neither SK&F 105561 nor SK&F 105809 antagonized the binding of LTB4 or leukotriene D4 to membrane receptors [5].
Oral administration of SK&F 105809 to rats resulted in a dose-related generation of SK&F 105561 and in the inhibition of thromboxane B2 and LTB4 production ex vivo with a half-maximal dose (ED50) of 15 and 60 mg/kg, respectively [5].
Treatment with SK&F 105809 (30 and 100 mg/kg p.o.) delivered 30 min prior to LPS resulted in 90-100% inhibition of serum TNF [6].

Associations of Skf-105809 with other chemical compounds

Furthermore, in a murine model of endotoxin shock in which animals are injected with LPS in combination with D-galactosamine (D-gal), SK&F 105809 (10, 30, and 100 mg/kg p.o.), delivered 30 min prior to LPS/D-gal, caused a dramatic reduction in serum TNF (40-90%) and protected the animals from the lethal effects of this treatment [6].

Gene context of Skf-105809

The mixed lipoxygenase/cyclooxygenase inhibitor SK&F 105809 reduces cerebral edema after closed head injury in rat [2].

Analytical, diagnostic and therapeutic context of Skf-105809

SK&F 105809 was also effective in inhibiting mouse collagen-induced arthritis and associated acute-phase reactant protein [7].

References

Pyridinyl imidazoles inhibit the inflammatory phase of delayed type hypersensitivity reactions without affecting T-dependent immune responses. Reddy, M.P., Webb, E.F., Cassatt, D., Maley, D., Lee, J.C., Griswold, D.E., Truneh, A. Int. J. Immunopharmacol. (1994) [Pubmed]
The mixed lipoxygenase/cyclooxygenase inhibitor SK&F 105809 reduces cerebral edema after closed head injury in rat. Shohami, E., Glantz, L., Nates, J., Feuerstein, G. Journal of basic and clinical physiology and pharmacology. (1992) [Pubmed]
Analgetic activity of SK&F 105809, a dual inhibitor of arachidonic acid metabolism. Griswold, D.E., Marshall, P., Martin, L., Webb, E.F., Zabko-Potapovich, B. Agents Actions Suppl. (1991) [Pubmed]
Pharmacology of the pyrroloimidazole, SK&F 105809--II. Antiinflammatory activity and inhibition of mediator production in vivo. Griswold, D.E., Marshall, P.J., Lee, J.C., Webb, E.F., Hillegass, L.M., Wartell, J., Newton, J., Hanna, N. Biochem. Pharmacol. (1991) [Pubmed]
Pharmacology of the pyrroloimidazole, SK&F 105809--I. Inhibition of inflammatory cytokine production and of 5-lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acid. Marshall, P.J., Griswold, D.E., Breton, J., Webb, E.F., Hillegass, L.M., Sarau, H.M., Newton, J., Lee, J.C., Bender, P.E., Hanna, N. Biochem. Pharmacol. (1991) [Pubmed]
Beneficial effects of SK&F 105809, a novel cytokine-suppressive agent, in murine models of endotoxin shock. Olivera, D.L., Esser, K.M., Lee, J.C., Greig, R.G., Badger, A.M. Circ. Shock (1992) [Pubmed]
Pharmacological profile of SK&F 105809, a dual inhibitor of arachidonic acid metabolism. Hanna, N., Marshall, P.J., Newton, J., Schwartz, L., Kirsh, R., Dimartino, M.J., Adams, J., Bender, P., Griswold, D.E. Drugs under experimental and clinical research. (1990) [Pubmed]

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