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Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in
James S Scott1, Andrew Bailey1, Robert D M Davies1
1Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
Abstract:
A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat.
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