Computer-aided Molecular Design Of New Active Compounds Against Terrorism

Fentanyl is a highly selectiveμ-opioid agonist. Due to its high analgesic potency and generally favourable pharmacological profile, it is clinically widely used for the narcotic analgesic. However,because of it is lethiferous, its usage is limited. We proposed to design a novel anti-terrist compound using fentanyl derivatives as leading compound, which will has hign analgesic activity and be low lethiferous. The methods is as follows:1.A GALAHAD screening is performed using fentanyl derivatives.2.A activity-reliable fentanyl derivatives is aligned on the pharmacophore obtained, and a CoMFA model which is useful on leading compound screening and new compound rebuilding is formed.3.Molecules complying with the pharmacophore obtained are searched in database.4.A screening is further performed using Docking and CoMFA model.5.A constructure rebuilding is conducted on the compounds which are obtained by screening, using CoMFA model.In present study, the steps 1, 2 and 3 are conducted.50 molecules were selected to produce the 3D pharmacophors. The 50 molecules were divided into one trainingset and one testset by means of chemical as well as biological diversity. The pharmacophores were tested with the testset molecules. Then 50 molecules were aligned on the pharmacophore to build the CoMFA Model. At last,the molecules complied with the pharmacophore were searched, which will be further studied.