Abstract:Die Triphenylbutyrolactone (I) werden mit Diisobutylaluminiumhydrid (DIBAH) zu den Triphenylfuranen (II) reduziert, die mit den entsprechenden Chloriden (III) zu den Aminoäthyläthern (IV) reagieren.
“…The results of these initial screening assays are summarized in Figure . 2 Representative furans and pyrroles explored as antifertility agents. − 3 Transcriptional activation data for furans 15a − c and 15g through ERα and ERβ. Human endometrial cancer (HEC-1) cells were transfected with expression vectors for ERα or ERβ and an estrogen responsive reporter gene and were treated with indicated concentrations of estradiol or ligand for 24 h to assay for agonism (diagonal slashed bars) or antagonism (crosshatched bars).…”
Section: Resultsmentioning
confidence: 99%
“…Several furans (3)(4)(5) and pyrroles (6-8) have been described as potential antifertility agents. [26][27][28][29] Few, however, showed significant activity, the most active being the furans (3)(4)(5), and binding and transcriptional activity were reported only in one instance. 26 In this report we describe an investigation of single heteroatom-containing five-membered ring heterocyclic analogues of the high-affinity pyrazole ligands.…”
mentioning
confidence: 99%
“…While certain azoles, such as oxazoles, thiazoles, isoxazoles, and imidazoles, did not produce good ER ligands in our hands, we wondered whether other five-membered ring heterocycles bearing only one heteroatom, namely, furans, thiophenes, and pyrroles, might provide ER ligands with interesting biological character. Several furans ( 3 − 5 ) and pyrroles ( 6 − 8 ) have been described as potential antifertility agents. − Few, however, showed significant activity, the most active being the furans ( 3 − 5 ), and binding and transcriptional activity were reported only in one instance …”
A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavior as ER ligands. An aldehyde enone conjugate addition approach and an enolate alkylation approach were developed to prepare the 1,4-dione systems that were precursors to the trisubstituted and tetrasubstituted systems, respectively. All of the diones were easily converted into the corresponding furans, but formation of the thiophenes and pyrroles from the more highly substituted 1,4-diones was problematical. Of the systems investigated, the tetrasubstituted furans proved to be most interesting. They were ER alpha binding- and potency-selective agents, with the triphenolic 3-alkyl-2,4,5-tris(4-hydroxyphenyl)furans (15a-d) displaying generally higher subtype binding selectivity than the bisphenolic analogues (15f-i). Binding selectivity for ER alpha was as high as 50-70-fold, and transcriptional activation studies showed that several members of this series were ER alpha selective agonists, with the best compound [3-ethyl-2,4,5-tris(4-hydroxyphenyl)furan, 15b] having full transcriptional activity on ER alpha while being inactive on ER beta. Comparative binding affinity analysis and molecular modeling were used to investigate the preferred binding mode adopted by the furan ligands, which appears to have the C(2) phenol mimicking the important role of the A-ring of estradiol. These ligands should be useful in studying the biological roles of both ER alpha and ER beta, and they might form the basis for the development of novel estrogen pharmaceuticals.
“…The results of these initial screening assays are summarized in Figure . 2 Representative furans and pyrroles explored as antifertility agents. − 3 Transcriptional activation data for furans 15a − c and 15g through ERα and ERβ. Human endometrial cancer (HEC-1) cells were transfected with expression vectors for ERα or ERβ and an estrogen responsive reporter gene and were treated with indicated concentrations of estradiol or ligand for 24 h to assay for agonism (diagonal slashed bars) or antagonism (crosshatched bars).…”
Section: Resultsmentioning
confidence: 99%
“…Several furans (3)(4)(5) and pyrroles (6-8) have been described as potential antifertility agents. [26][27][28][29] Few, however, showed significant activity, the most active being the furans (3)(4)(5), and binding and transcriptional activity were reported only in one instance. 26 In this report we describe an investigation of single heteroatom-containing five-membered ring heterocyclic analogues of the high-affinity pyrazole ligands.…”
mentioning
confidence: 99%
“…While certain azoles, such as oxazoles, thiazoles, isoxazoles, and imidazoles, did not produce good ER ligands in our hands, we wondered whether other five-membered ring heterocycles bearing only one heteroatom, namely, furans, thiophenes, and pyrroles, might provide ER ligands with interesting biological character. Several furans ( 3 − 5 ) and pyrroles ( 6 − 8 ) have been described as potential antifertility agents. − Few, however, showed significant activity, the most active being the furans ( 3 − 5 ), and binding and transcriptional activity were reported only in one instance …”
A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavior as ER ligands. An aldehyde enone conjugate addition approach and an enolate alkylation approach were developed to prepare the 1,4-dione systems that were precursors to the trisubstituted and tetrasubstituted systems, respectively. All of the diones were easily converted into the corresponding furans, but formation of the thiophenes and pyrroles from the more highly substituted 1,4-diones was problematical. Of the systems investigated, the tetrasubstituted furans proved to be most interesting. They were ER alpha binding- and potency-selective agents, with the triphenolic 3-alkyl-2,4,5-tris(4-hydroxyphenyl)furans (15a-d) displaying generally higher subtype binding selectivity than the bisphenolic analogues (15f-i). Binding selectivity for ER alpha was as high as 50-70-fold, and transcriptional activation studies showed that several members of this series were ER alpha selective agonists, with the best compound [3-ethyl-2,4,5-tris(4-hydroxyphenyl)furan, 15b] having full transcriptional activity on ER alpha while being inactive on ER beta. Comparative binding affinity analysis and molecular modeling were used to investigate the preferred binding mode adopted by the furan ligands, which appears to have the C(2) phenol mimicking the important role of the A-ring of estradiol. These ligands should be useful in studying the biological roles of both ER alpha and ER beta, and they might form the basis for the development of novel estrogen pharmaceuticals.
“…Furans are found in many natural products (Keay and Dibble, 1996) and as a result of their biological activity, they are often structural moieties in pharmaceuticals (Iyer and Gopalachari, 1973;Dikshit et al, 1974;Durani et al, 1989;Dikshit et al, 1991;Nieves-Neira et al, 1999;Mortensen et al, 2001;Chène, 2003;Issaeva et al, 2004;Thuita et al, 2008;Wenzler et al, 2009;Barrett and Croft, 2012). The Molisch test is a colometric detection method that can be used to detect carbohydrates that have been converted into furfuraldehydes by thermal acid degradation.…”
Multicomponent reactions, conducted in a domino, sequential or consecutive fashion, have not only considerably enhanced synthetic efficiency as one-pot methodology, but they have also become an enabling tool for interdisciplinary research. The highly diversity-oriented nature of the synthetic concept allows accessing huge structural and functional space. Already some decades ago this has been recognized for life sciences, in particular, lead finding and exploration in pharma and agricultural chemistry. The quest for novel functional materials has also opened the field for diversity-oriented syntheses of functional π-systems, i.e. dyes for photonic and electronic applications based on their electronic properties. This review summarizes recent developments in MCR syntheses of functional chromophores highlighting syntheses following either the framework forming scaffold approach by establishing connectivity between chromophores or the chromogenic chromophore approach by de novo formation of chromophore of interest. Both approaches warrant rapid access to molecular functional π-systems, i.e. chromophores, fluorophores, and electrophores for various applications.
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