title: Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat.
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.
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: James S
authors.initials: JS
authors.lastname: Scott
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bailey
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Robert D M
authors.initials: RD
authors.lastname: Davies
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Sébastien L
authors.initials: SL
authors.lastname: Degorce
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Philip A
authors.initials: PA
authors.lastname: MacFaul
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Helen
authors.initials: H
authors.lastname: Gingell
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moss
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Norman
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Pink
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Rabow
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Bryan
authors.initials: B
authors.lastname: Roberts
authors.affiliation: Oncology iMed, AstraZeneca , Mereside, Alderley Park, Macclesfield, SK10 4TG, U.K.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Smith
keywords: Estrogen receptor; antagonist; bioavailable; downregulator; phenol; tetrahydroisoquinoline
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