Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens
| Autor: | Jae Chon Jo, Hee An Kwon, Masahiro Nishimoto, Iwao Ohizumi, Toshiaki Tsunenari, Hak Yeop Kim, Kenji Taniguchi, Yoshitake Kanbe, Yoshiaki Nabuchi, Shin ichi Kaiho, Yoshihito Ohtake, Myung Hwa Kim, Setsu Kawata, Kazumi Morikawa, Hyun-Suk Lim |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
chemistry.chemical_classification
Stereochemistry Organic Chemistry Clinical Biochemistry Pharmaceutical Science Administration Oral Sulfoxide Biological activity Antiestrogen Biochemistry Sulfonamide chemistry.chemical_compound chemistry Estrogen Receptor Modulators Oral administration Area Under Curve Drug Discovery Side chain Molecular Medicine Moiety Chromans skin and connective tissue diseases Molecular Biology hormones hormone substitutes and hormone antagonists Sulfamide |
| Zdroj: | Bioorganicmedicinal chemistry letters. 16(15) |
| ISSN: | 0960-894X |
| Popis: | In order to search for alternatives to the sulfoxide moiety in the long side chain of pure antiestrogens, several molecules that may interact with water in a fashion similar to ICI164,384 were designed and it was found that compounds with the carboxy, the sulfamide, or the sulfonamide instead of the sulfoxide moiety also functioned as pure antiestrogens. Interestingly, the compound possessing the carboxy moiety showed superior antiestrogen activity compared to ICI182,780 when dosed orally. Results of the pharmacokinetic evaluation indicated that the potent antiestrogen activity at oral dosing attributed to both the improved absorption from the intestinal wall and the metabolic stability of the compound in liver. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect