Metabolites and derivatives of ambrisentan
View Patent ↗The invention relates to derivatives and metabolites of ambrisentan, including compounds of general Formula (I) or salts, hydrates, solvates, racemates, or optical isomers thereof, wherein R 1 is —OH or —OCH 3 ; R 2 is —H, lower alkyl (e.g. C 1 -C 4 alkyl) or glycosidyl; and R 3 and R 4 are independently —CH 3 , —C(O)H or —CH 2 OR 6 , wherein R 6 is —H or a hydrocarbyl group having 1 to 20 carbon atoms.
1. A method for identifying a metabolite of ambrisentan comprising: administering ambrisentan to a mammal and
detecting and/or measuring a level or concentration of a metabolite of ambrisentan in tissues or bodily fluids of the mammal,
wherein the metabolite comprises a compound which is selected from:
and pharmaceutically acceptable salts thereof.
2. The method according to claim 1 , wherein the bodily fluids are selected from the group consisting of plasma, bile, urine, and feces.
3. The method according to claim 1 , comprising detecting nuclear decay products from a 3 H or 14 C labeled ambrisentan molecule administered to the mammal.
4. The method according to claim 1 , comprising administering 13 C enhanced ambrisentan to the mammal.
5. The method according to claim 1 , wherein the metabolite has an S configuration about the asymmetric carbon.