High affinity tamoxifen derivatives and uses thereof

US5192525A · kind A · utility

Assignee

• The Board of Regents of the University of Texas System · US

Inventors

• David J. Yang · Sugar Land, US
• Sidney Wallace · Houston, US

Key dates

• Filing date: Jun 28, 1991
• Grant date: Mar 9, 1993
• Expiry date: Jun 28, 2011

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C217/18
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The synthesis of tamoxifen derivatives, most particularly halo, haloalkyl and hydroxy tamoxifen derivatives, wherein the native tamoxifen molecule includes a substituted chemical group positioned on the aliphatic chain of the tamoxifen molecule, is provided. Methods for imaging estrogen receptors using the tamoxifen derivatives of the invention are also described. The aliphatic chain substituted tamoxifen derivatives of the invention possess greater estrogen receptor binding affinities and more potent tumor cell inhibiting activity than native tamoxifen or tamoxifen derivatives substituted at other locations on the molecule (i.e., non-aliphatic chain substituted tamoxifen, phenolic-ring substituted tamoxifen). Examples of the halogenated tamoxifen derivatives of the invention include chloro-, bromo-, iodo- and fluoro-tamoxifen derivatives, and their corresponding lower alkyl halogenated forms.