Leichtl, Stefan and von Angerer, Erwin (1998) 2-phenylbenzo[b]thiophene-based antiestrogens with mammary tumor inhibiting activity. ARCHIV DER PHARMAZIE, 331 (9). pp. 283-289. ISSN 0365-6233, 1521-4184
Full text not available from this repository.Abstract
In this study we extended our studies on heterocyclic antiestrogens to 2-phenylbenzo[b]thiophenes which can be considered as isosteric to the 2-phenylindole system. We synthesized a number of 6-hydroxy-2-(4-hydroxyphenyl)benzo [b]thiophenes with carbamoyl and amino functions in the side chain at carbon-3 and analyzed their biological properties. The binding affinities for the estrogen receptor are mainly influenced by the chain length where-as the hormonal profile depends on the nature of the functional group. From this study 3-[10-(2,2,3,3,4,4,4-heptafluorobutyl-methylcarbamoyl)decyl] -6-hydroxy- 2-(4-hydroxyphenyl)benzo-[b]thiophene (6e) emerged as an antiestrogen with all the characteristics of a pure antagonist. It did not stimulate gene expression in HeLa cells cotransfected with the expression vector for the human estrogen receptor HEG0 and the luciferase reporter plasmid EREwtc luc nor did it show any estrogenic activity in the mouse uterus weight test. In the latter assay, it completely abrogated theory effect of estrone. Due to its antiestrogenic potency it inhibited the growth of estrogen-sensitive human MCF-7 breast cancer cells with an IC50 value of 5 nM. These data suggest that an amide function in combination with the fluorination of the terminal carbon atoms is an appropriate modification to abolish the estrogenic action of the 2-phenylbenzothiophene system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ESTROGEN-RECEPTOR AFFINITY; CLINICAL BREAST-CANCER; PURE ANTIESTROGENS; ANTAGONIST; TAMOXIFEN; MICE; ICI-182780; RATS; benzothiophene; antiestrogen; in vitro antitumour activity; transfection assay |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Feb 2023 09:22 |
| Last Modified: | 16 Feb 2023 09:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49522 |
Actions (login required)
 |
View Item |
