title: Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction.
abstract: In order to find novel nonsteroidal compounds possessing an inhibitory activity against delayed-type hypersensitivity (DTH) reactions, we conducted random screening using a picryl chloride (PC)-induced contact hypersensitivity reaction (CHR) in mice, and found compound 1 as a lead compound. Then we synthesized and evaluated an extensive series of 5-carboxamidouracil derivatives focused on both the uracil and the antioxidative moieties. Among them, we found that the hindered phenol moiety was necessary to exhibit the activities; especially, compounds 28a-28c having the partial structure of vitamin E were found to exert potent activities against the DTH reaction by both oral and topical administration. And compound 28c showed antioxidative activity against lipid peroxidation with an IC50 of 5.9 microM. Compound 28c (CX-659S) was chosen as a candidate drug for the treatment of cutaneous disorders such as atopic dermatitis and allergic contact dermatitis.
authors.affiliation: Pharmaceutical and Biotechnology Laboratory, Japan Energy Corporation, Saitama.
authors.forename: M
authors.initials: M
authors.lastname: Tobe
authors.forename: Y
authors.initials: Y
authors.lastname: Isobe
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: F
authors.initials: F
authors.lastname: Obara
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: J
authors.initials: J
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D001923:Brain Chemistry; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010853:Picryl Chloride; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D000975:Antioxidants; D014498:Uracil; C418807:CX 659S; D010853:Picryl Chloride