title: Docking, Molecular Dynamics Simulation and Synthesis of New Fenobam Analogues as mGlu5 Receptor Antagonists.
abstract: BACKGROUND
  Fenobam is a non-competitive mGluR5 antagonist as an anxiolytic agent.
  
  
  OBJECTIVE
  In this research a new series of fenobam analogues containing thiazole moiety instead of imidazole ring were designed and synthesized.
  
  
  METHODS
  The ureido-substituted products were synthesized from reaction of amino thiazole derivatives and isocyanate derivatives in dichloromethane solvent under microwave and ultrasonic irradiation condition. The synthesized compounds structures were established by means of IR, 1HNMR, 13CNMR spectroscopic data. Then, docking calculations were performed on the active site of mGLuR5 and compared to Fenobam as a reference drug by using AutoDock program. The molecular dynamics (MD) simulations were done using GROMACS 5.0.5.
  
  
  RESULTS
  Docking studies suggested that all of the compounds possess better binding energy when compared to fenobam. The results of MD simulations might offer the binding mode of ligand (3b), accuracy of docking and the reliability of active conformations which obtained by AutoDock.
  
  
  CONCLUSIONS
  New derivatives of fenobam were designed and synthesized that have the better insilico results compared to fenobam and will evaluate in future studies.
authors: Abdollah
authors: A
authors: Javidan
authors: Mohammad Javad
authors: MJ
authors: Taghizadeh
authors: Seyed Ayoub
authors: SA
authors: Hosseini
authors: Chemical Injuries Research Center, Baqiyatallah University of Medical Science, Molla-Sadra Street, P.O. Box: 19945-581, Tehran, Iran. m-iman@alumnus.tums.ac.ir.
authors: Maryam
authors: M
authors: Iman
authors: Rahim
authors: R
authors: Jafari
mesh_terms: D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D014151:Anti-Anxiety Agents; D007093:Imidazoles; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; C032794:fenobam