29745-42-4Relevant academic research and scientific papers
Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor based alignment
Iskander, Magdy N.,Leung, Lok M.,Buley, Trevor,Ayad, Fadi,Di Iulio, Juliana,Tan, Yean Y.,Coupar, Ian M.
, p. 16 - 26 (2006)
Twenty two 5-HT4 agonists obtained from our laboratory and the recent literature were used to develop a CoMFA model to predict 5-HT4 agonist activity. Two models were produced and compared for predictivity, the first by alignments ba
Synthesis, testing and structure-activity studies on a library of 5-HT 4 ligands
Hanna-Elias, Amir,Manallack, David T.,Levit, Alla,Nguyen, William,Ayad, Fadi,Perera, Glen,Shapiro, Marina,Irving, Helen R.,Coupar, Ian M.,Iskander, Magdy N.
experimental part, p. 344 - 354 (2012/05/19)
Several indole derivatives and analogues comprising a range of related structural classes were designed, synthesized and tested as ligands for the 5-HT4 receptor. Within each series, binding experiments showed compounds with good affinity demonstrating high percentage displacement values at 1 μM. The most potent of these (20) had a pKi of 8.54 demonstrating very good affinity. These indole analogues were combined with 55 ligands that were previously produced in our laboratory to explore the structure-activity relationships of these 5-HT4 ligands. A CoMFA (Comparative Molecular Field Analysis) analysis was used to extend an earlier simple pharmacophore to suggest two new molecular features beyond the primary amino binding site. The pharmacophore confirmed that a newly described tetrahydroquinoline analogue was able to match the basic requirements of the model and the pharmacology of this molecule is provided in more detail.
