title: Novel antiallergic agents. Part I: Synthesis and pharmacology of pyrimidine amide derivatives.
abstract: We have synthesized many pyrimidine amide derivatives. Novel pyrimidine bis-glycolic amide derivatives showed moderate inhibition in the rat passive cutaneous anaphylaxis (PCA) assay by oral administration. Among these compounds, 2,4-bis(methoxyacetylamino)-6-piperidinopyrimidine (2i) exhibited significant inhibition. However the compound (2i) did not inhibit antigen-induced histamine or SRS-A release from lung fragments of the guinea-pig at less than 10(-4) M. Derivatives of 2i have also notable or moderate activity in the rat PCA assay. Compound 2h which has no oxygen atom at the alpha-position of the amide carbonyl group and, compound 17 which has no amide carbonyl group, showed no inhibition in the rat PCA assay. We supposed that both the amide carbonyl group and the oxygen atom at alpha-position of the amide carbonyl group play an important role in inhibiting the rat PCA reaction. These pyrimidine bis-glycolic amide derivatives have a novel structure and unique activity which suggests they may be potentially useful in the treatment of allergic diseases.
authors.affiliation: Pharmaceuticals Research Center, TOYOBO Co., Ltd, Ohtsu, Shiga, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ban
authors.forename: H
authors.initials: H
authors.lastname: Taguchi
authors.forename: T
authors.initials: T
authors.lastname: Katsushima
authors.forename: S
authors.initials: S
authors.lastname: Aoki
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013189:SRS-A / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D018926:Anti-Allergic Agents; D011743:Pyrimidines; D013189:SRS-A