A New Series of Estrogen Receptor Modulators: Effect of Alkyl Substituents on Receptor-Binding Affinity

Abstract

New types of selective estrogen receptor modulators (SERMs) were synthesized and evaluated for their binding affinity and biological effect on reproductive cells. A proposed lead structure (B) was derivatized to provide compounds 30 and 44, which showed good estrogen-receptor binding affinity (K i values: 6.3 and 10 nM, respectively), as well as minimal impact on mammary and uterine carcinoma cells. Introduction of an alkyl group in the core structure considerably enhanced receptor-binding affinity of the compounds tested. Synthesis and structure-activity relationships of these compounds are described.

Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta

“…Starting with ketone 9 , the alkyl chains were introduced by enolate alkylation to obtain the substituted ketones 29a , 30a and 31 within only 30 min at room temperature. In accordance with literature precedent [35], an excess of base and alkylating agent gave the monoalkylated products in good yields, together with much smaller amounts of the corresponding bis-alkylated compounds. Since the enolate is not preformed in that procedure, it is noteworthy that when one equivalent of base and iodoalkane were used, only a single alkyl chain was introduced selectively.…”

Diverse Visible‐Light‐Promoted Functionalizations of Benzotriazoles Inspired by Mechanism‐Based Luminescence Screening

“…Va rious styrenes with different electronic properties could be employed affording alkylated products 8d-8i in moderate to good yields (30-68 %). Theo btained products have,t othe best of our knowledge,n ot been described previously.H owever, related structural motifs can be found in several novel drug candidates for the regulation of estrogen receptors [16] and for the inhibition of factor Xa. [17] In accordance with other Meerwein-type addition processes of aryl radicals,a liphatic alkenes,which are comparatively poor radical acceptors,were not suitable coupling partners.…”

Durch sichtbares Licht vermittelte Funktionalisierungen von Benzotriazolen, inspiriert durch mechanismusbasiertes Lumineszenz‐ Screening

“…Die erhaltenen Produkte sind unseres Wissens bislang noch nicht beschrieben worden. Allerdings lassen sich strukturell ähnliche Motive in verschiedenen Wirkstoffkandidaten zur Regulation von Estrogen‐Rezeptoren oder zur Inhibition des Faktors Xa finden . In Übereinstimmung mit anderen Meerwein‐Additionsprozessen von Arylradikalen sind Alkylolefine, die vergleichsweise schlechte Radikalakzeptoren sind, keine geeigneten Kupplungspartner.…”