A Structure Based, Solid Phase Synthesis Approach to the Development of Novel Selective Estrogen Receptor Modulatory Steroids

Abstract

The objective of this project is the development of new chemotherapeutic agents for the treatment of hoemone-responsive breast cancer using a structure-based solid phase synthesis approach. During the past year we have utilized our functionalized resin to prepare a second series of carboxamido-phenylvinyl estradiols. The compounds were characterized by NMR and analyzed by computational methods. The new agents were evaluated for estrogen receptor binding affinity and in vivo efficacy. The results suggest that incorporation of functional groups at the specific sites proposed reduces both affinity and efficacy, however, positional isomers and configurational isomers had better activity. These observations have been incorporated into the design of the second generation steroids that will be prepared and evaluated in the third year of the project.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2001
Accession Number
ADA403350

Entities

People

  • Robert N. Hanson

Organizations

  • Northeastern University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Alkenes
  • Chemical Synthesis
  • Chemistry
  • Computational Science
  • Drug Abuse
  • Health Services
  • Hormones
  • Organic Chemistry
  • Radioactive Decay
  • Radiotherapy
  • Regression Analysis
  • Solid Phases
  • Statistical Analysis
  • Two Dimensional

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry
  • Organic Chemistry