Tomoyuki Koshi

Synthesis and bioactivities of novel pyridazine derivatives: inhibitors of interleukin-1 beta (IL-1β) production

New pyridazine derivatives were prepared, and their abilities to inhibit IL-1beta production were evaluated. Some compounds showed potent inhibitory activity against IL-1beta production in HL-60 cells stimulated with lipopolysaccharide (LPS). The synthesis and structure-activity relationships of these compounds are described.

Synthesis and bioactivities of novel 5,6-bis(4-methoxyphenyl)2H-pyridazin-3-one derivatives : Inhibitors of interleukin-1 beta (IL-1β) production

New 5,6-bis(4-methoxyphenyl)-2H-pyridazin-3-one derivatives were prepared, and their abilities to inhibit IL-1beta production were evaluated. Some compounds showed potent inhibitory activity against IL-1beta production in HL-60 cells stimulated with lipopolysaccharide (LPS). The synthesis and structure-activity relationships of these compounds are described.

Characterization of immunoreactive endothelin in human urine

We developed three antibodies, specific and sensitive to endothelin-1 (ET-1), and established two sandwich and three competitive enzyme immunoassays (EIAs). By using these EIAs, large immunoreactive ET (IR-ET) of molecular weight 10 k Da was identified as a main component of IR-ETs in human urine. This large IR-ET, which reacted with two antibodies specific for N-terminal region of ET-1 but not with the antibody against C-terminal peptide of ET-1, was partially purified by six-step procedure and examined by Western blotting after SDS polyacrylamide gel electrophoresis. The large IR-ET was detected as a single band at molecular weight of 10 k Da both in reduced and non-reduced conditions. From these results, the large IR-ET was thought to consist of a single polypeptide chain and possess the steric restricted N-terminal region of ET-1.

Pyrogenic action of endothelin in conscious rabbit

Injection of 0.3 nmol/kg endothelin(ET)-1 into the ear vein of conscious rabbits induced a significant increase in body temperature. ETB receptor specific agonist, namely 4-Ala-ET-1, also caused an elevation of the body temperature in a dose-dependent manner by injection into the ear vein of rabbit. These results suggest that ET play important roles in regulation of body temperature through selective stimulation of ETB receptor.

Quantitative structure-activity relationships study of endothelin-1 analogs

Abstract Endothelin-1 analogs replaced by various amino acids at position 20 [X20]-ET-1) were synthesized and evaluated for the ETA and ETB receptor binding activities. In order to obtain the structural requirements for the ETA and ETB receptor binding activities, the quantitative structure-activity relationships(QSAR) of sixteen analogs was investigated by the PLS method. The quantitative structuve-activity relationshis(QSAR) of endothelin-1 analogs([X20]-ET-1) replaced by various amino acids at position 20 was investigated by the PLS method.