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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.

SUBMITTER: Scott JS

PROVIDER: S-EPMC4716595 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat.

Scott James S JS Bailey Andrew A Davies Robert D M RD Degorce Sébastien L SL MacFaul Philip A PA Gingell Helen H Moss Thomas T Norman Richard A RA Pink Jennifer H JH Rabow Alfred A AA Roberts Bryan B Smith Peter D PD

ACS medicinal chemistry letters 20151219 1

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. ...[more]

PMID: 26819673

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