Novel thiazole derivatives as inhibitors of superoxide production by human neutrophils: synthesis and structure-activity relationships.
Neutrophils have an important role in the self-defense systems of organisms through the production of superoxide. On the other hand, it has been proposed that abnormal amounts of superoxide produced by neutrophils are a serious factor in tissue injury. A series of novel thiazole derivatives was prepared and evaluated inhibitory effect on superoxide production by human neutrophils in vitro. Among these compounds, 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl]-pyridine-2-carboxylic acid (OPC-6535) was selected as one of the most promising compounds. The synthesis and structure-activity relationships of these compounds are reported herein.
Chihiro
M
M
Second Institute of New Drug Research, Otsuka Pharmaceutical Company, Tokushima, Japan.
Nagamoto
H
H
Takemura
I
I
Kitano
K
K
Komatsu
H
H
Sekiguchi
K
K
Tabusa
F
F
Mori
T
T
Tominaga
M
M
Yabuuchi
Y
Y
D000328:Adult; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009504:Neutrophils / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D013844:Thiazoles; D013481:Superoxides