title: Immunomodulating action and structure-activity relationships of substituted phenylamides of 5-amino-3-methylisoxazole-4-carboxylic acid.
abstract: A series of 5-amino-3-methylisoxazole-4-carboxylic acid amides has been prepared by condensation of 5-amino-3-methylisoxazole-4-carboxylic acid with ethyl chloroformate. The resulting mixed anhydride undergoes condensation with appropriate phenylamides to form the corresponding amides 6-16. The compounds obtained were evaluated for their immunological activities in cultures of human peripheral blood mononuclear cells (PMBC). We found that the activities of the compounds in the proliferation test and in the lipopolysaccharide (LPS)-induced cytokine production in PBMC cultures were differential. The stimulatory or inhibitory effects depended strongly on the origin and location of substituents in the phenyl ring which is described in the discussion and was supported by QSAR studies.
authors.affiliation: University of Medicine, Faculty of Pharmacy, Dept. Organic Chemistry, Grodzka, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Ryng
authors.forename: M
authors.initials: M
authors.lastname: Zimecki
authors.forename: Z
authors.initials: Z
authors.lastname: Sonnenberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Mokrosz
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha