- 2-Phenylbenzo[b]thiophene-based antiestrogens with mammary tumor inhibiting activity
-
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 whereas 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 HEGO 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 the stimulatory effect of estrone. Due to its antiestrogenic potency it strongly 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 is combination with the fluorination of the terminal carbon atoms is an appropriate modification to abolish the estrogenic action of the 2- phenylbenzothiophene system.
- Leichtl, Stefan,Von Angerer, Erwin
-
p. 283 - 289
(2007/10/03)
-
- 2-phenylbenzo[B]furans, process for their manufacture and pharmaceutical preparations containing them
-
The invention relates to new furans and thiophenes with the general Formula 1, STR1 in which R1 and R2 independently of one another denote a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a benzyl group, a group C(O)R4, where R4 is an alkyl or alkoxy group having 1 to 10 carbon atoms or a phenyl radical, or a carbamoyl group --C(O)NR5 R6, where R5 and R6 independently of one another are a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n denotes an integer from 0 to 12 if R3 is a hydrogen atom, or n denotes an integer from 4 to 12 if R3 is an amino group --NR7 R8, where R7 and R8 independently of one another represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms or R7 and R8 together represent an alkylene group --(CH2)m -- or the group --(CH2)2 -- or R3 denotes an amide group --C(O)NR7 R 8, where R7 and R8 have the abovementioned meanings, or R3 denotes a sulphinyl group --S(O)R3, where R9 is the radical --(CH2)m (CF2)o CF3 and m and o are 2, 3, 4, 5 or 6 and x denotes an oxygen or sulphur atom. These new compounds are strong and selective anti-oestrogens, and have therapeutic applications in the treatment of oestrogen-related illnesses.
- -
-
-