Synthesis of Pyrimidine Derivatives Possessing an Antioxidative Property and Their Inhibitory Effects on Picryl Chloride-Induced Contact Hypersensitivity Reaction

• Published in: Chemical & pharmaceutical bulletin Vol. 51; no. 12; pp. 1451 - 1454
• Main Authors: Isobe, Yoshiaki, Hirota, Kosaku
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.12.2003; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Anti-Allergic Agents - chemical synthesis; Anti-Allergic Agents - therapeutic use; Antioxidants - chemical synthesis; Antioxidants - therapeutic use; antioxidative activity; barbituric acid; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; delayed type hypersensitivity (DTH); Dermatitis, Contact - prevention & control; di-t-butylphenol; Life Sciences & Biomedicine; Male; Medical sciences; Mice; Mice, Inbred ICR; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Picryl Chloride - toxicity; Pyrimidines - chemical synthesis; Pyrimidines - therapeutic use; Rats; Science & Technology; uracil; PATHOGENESIS; VITAMIN-E; di-t-butylphenol; delayed type hypersensitivity (DTH); DERMATITIS; uracil; antioxidative activity; barbituric acid; PSORIASIS; Rodentia; Antiinflammatory agent; Lipids; Delayed hypersensitivity; Antioxidant; Vertebrata; Mammalia; Structure activity relation; Mouse; Animal; Phenols; Pyrimidine derivatives; Oxidation; Fluorine Organic compounds; Hydrazone; Barbiturates; Chemical synthesis; Peroxidation
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.51.1451

We conducted a preliminary structure–activity relationship (SAR) study of some barbituric acid and uracil derivatives against the picryl chloride-induced contact hypersensitivity reaction. The introduction of an antioxidative moiety to the side chain of the C(6)-position of uracil was effective against this model. The introduction of dimethoxyphenol (8b) or dimethylphenol (8c) instead of di-t-butylphenol (8a) as an antioxidative moiety gave diminished activities, so, the reactive oxygen would contribute to the inflammation of this model, and an antioxidative activity was required for exhibiting the inhibitory activity. The inhibitory activity was significantly affected by the substituent at the N(1)-phenyl moiety.