ABSTRACT
An indazole based series of glucocorticoid receptor agonists is reported. The SAR exploration of this scaffold yielded compounds with nanomolar affinity for the glucocorticoid receptor with indications of selectivity for the preferred transrepression mechanism; in vivo efficacy was observed in the mouse LPS induced TNFalpha model for compound 28.
Subject(s)
Anti-Inflammatory Agents/chemistry , Indazoles/chemistry , Receptors, Glucocorticoid/agonists , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Indazoles/chemical synthesis , Indazoles/pharmacology , Mice , Receptors, Glucocorticoid/metabolism , Tumor Necrosis Factor-alpha/metabolismSubject(s)
Adhesives/poisoning , DNA Damage , Occupational Exposure , Solvents/poisoning , Brazil , Humans , Industry , ShoesABSTRACT
The synthesis of benzo[c]phenanthridine alkaloid derivatives is described. In vitro antiviral activity against herpes simplex type 1 (HSV1) has been investigated. Contrary to the natural product fagaronine, which did not have any activity in the HSV1 antiviral tests, four 12-alkoxy derivatives showed good activity demonstrating the importance of the 12-substitution in the structure-activity relationships.