Preview
Sign-in for full Details 
Sign-in free and Explore the Exciting World of BiomedExperts:
- Over 1,800,000 Profiles
- More than 3,500 Organizations worldwide
- State of the Art Network Visualizations
- Manage your own Profile
- Locate Experts in your Country/Region
- Locate Experts in your 1. and 2. Level Network
- Connect to Experts Worldwide
find experts for
Sign-in to see more
2003:
Minutolo Filippo; Antonello Michela; Bertini Simone; Ortore Gabriella; Placanica Giorgio; Rapposelli Simona; Sheng Shubin; Carlson Kathryn E; Katzenellenbogen Benita S; Katzenellenbogen John A; Macchia Marco
Novel estrogen receptor ligands based on an anthranylaldoxime structure: role of the phenol-type pseudocycle in the binding process.
Journal of medicinal chemistry 2003;
46(
19):.
The 3,4-diphenylsalicylaldoxime system 1 is an estrogen receptor (ER) ligand of unusual structure, having a hydrogen-bonded pseudocyclic A'-ring in place of the paradigmatic phenolic A-ring that is characteristic of most estrogens. We have investigated the role played by the pseudocycle A' in binding to the ER by preparing 3,4-diphenylbenzaldoxime (4), a compound that completely lacks this ring but still preserves all of the other features of the original molecule 1, as well as a series of 3,4-diphenylanthranylaldoximes (5a-c) in which the nature of the heteroatom participating in the formation of pseudoring A' has been changed from an oxygen (1) to a nitrogen that is either unsubstituted (5a) or substituted with small alkyl groups (a methyl in 5b, or an ethyl in 5c). The importance of hydrogen-bonded pseudocycle A' in the binding process was confirmed by the fact that benzaldoxime 4 showed a greatly reduced binding affinity compared to salicylaldoxime 1. Moreover, the binding affinity improved considerably when the A'-ring contained either an unsubstituted nitrogen (5a) or an N-Me group (5b). On the other hand, the N-Et-substituted anthranyl derivative 5c showed a marked drop in binding affinity. Molecular modeling docking studies on ERalpha confirmed that compounds 5a and 5b fit nicely in the ligand binding pocket, with an especially comfortable fit for the N-Me group of 5b in a small hydrophobic pocket surrounded by nonpolar residues. The limited size of this pocket does not allow accommodation of N-substituents larger than a methyl group, which is consistent with the low binding affinity of the N-Et compound 5c.
Post to CiteULike 
Sign in free and see...
Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more
