High affinity tamoxifen derivatives

US6096874A · kind A · utility

Assignee

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

Inventors

• Sidney Wallace · Houston, US
• David J. Yang · Sugar Land, US
• E. Delpassand · Bellaire, US
• A. Cherif · Houston, US
• S. Quadri · Houston, US

Key dates

• Filing date: Jun 7, 1995
• Grant date: Aug 1, 2000
• Expiry date: Jun 7, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C237/10
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The synthesis of tamoxifen derivatives, most particularly halo, halo alkyl, hydroxy, and amino tamoxifen derivatives is disclosed. The native tamoxifen molecule includes a substituted chemical group positioned on the aliphatic chain of the tamoxifen molecule. Particular tamoxifen derivatives of the invention include chloro, bromo, iodo, fluoro, amino and DTPA tamoxifen derivatives, and corresponding lower alkyl halogenated forms. The halogenated tamoxifen derivatives possess superior binding affinities for estrogen receptor rich tissues, such as uterine tissue and breast tissue, relative to unsubstituted native tamoxifen. Radiolabeled forms of the tamoxifen derivatives may be used as highly specific imaging agents for estrogen receptor rich tissues. The fluoro and bromo tamoxifen derivatives are particularly useful for imaging estrogen receptors by PET whereas the iodinated tamoxifens are particularly useful in imaging estrogen receptors by SPECT. Rapid and efficient methods of preparing the tamoxifen derivatives having high specific activity (>6 Ci/.mu.mol) are also disclosed. Aliphatic chain substituted tamoxifen derivatives are shown to possess greater estrogen receptor binding …