Combinatorial Synthesis for the Expedited Discovery of Novel Selective Antiestrogens for Breast Cancer Prevention and Therapy
Final rept. 1 Sep 1997-31 Aug 2001
ILLINOIS UNIV CHAMPAIGN
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We have conceived of an approach to prepare by combinatorial methods, libraries of novel ligands for the estrogen receptor, by the creation of simple amide or five-membered ring heterocyclic core structures that display peripheral substituents phenols, aliphatic groups, etc. commonly found in non-steroidal estrogens. These novel estrogens might be useful in the treatment or prevention of breast cancer. We have made excellent progress on the preparation of novel estrogens of the diphenyl carboxamide class, the diphenylsulfonamide class, the phenyl benzylcarboxamide and sulfonamide classes, and the pyrazole, oxazole, thiazole, and imidazole classes. Members of some classes have high affinity for the estrogen receptor, and some of them show high binding and potency selectivity for the estrogen receptor subtype alpha and can be adapted as selective estrogen receptor alpha antagonists. We have also developed a convenient solid phase synthesis of the pyrazole class, so that we can prepare conveniently and rapidly larger libraries of the members of what appear presently to be the most promising of these classes of novel estrogens.
- Medicine and Medical Research