The Study On Drug Molecular Design For Anti-Influenza Virus Of HA And NA

Influenza virus has highly pathogenic and Variability caused constant threat to human health, it's urgently to study the new anti-influenza virus drugs, especially universally applicable anti-influenza drugs. The development of computer technology help Drug Research develop rapidly as result of Structure-based Drug Design and Receptor-based Drug Design. Televant computer programs and theoretical analysis fecilitate Drug Design on new drugs easy. This paper is divided into five chapters, use structural calculation software Gaussian 09 and statistical analysis methods for drug research and design. The first chapter is brief for the study, the second chapter is quantum chemical agents used to study anovel pyrimidine compounds as neuraminidase inhibitors, the third chapter is QSAR studies used to research N-substituted oseltamivir derivative as NA inhibitors, fourth chapter is QSAR methods study benzenesulfonamide derivatives as potent anti-influenza hemagglutinin inhibitors, Chapter V is molecular design as anti-influenza drugs while inhibit NA and HA activated.Chapter I: Description of the Computer-aided Drug Design methods in quantum chemistry. The structure and characteristics of influenza viruses were introduced. It introduces status and direction of research and some problems facing to the Anti-influenza Virus Drugs. HA and NA are associated with sialic acid on influenza virus replication process, studie NA and HA inhibitor are offen apply sialic acid to a substrate, and thus proposes innovative research and design new drug molecular have dual inhibition betwen HA and NA is provided with great significance.Chapter II: Paper reported a 6-oxo-1,4,5,6-tetrahydro-5-carboxylic acid derivatives of the NA inhibitors with good inhibitory activity. Research those selected good activity of several molecules using density functional theory of quantum chemical calculations, combined with pyrimidine compounds reported in the literature on the NA inhibitory activity data were obtained from structure activity relationship. Provide a theoretical basis for further study of the structure-activity relationship among NA inhibitors.Chapter III: Currently, oseltamivir as NA inhibitors are widly used due to poor oral bioavailability and the emergence of resistance cause Oseltamivir Derivatives research had been an important direction of new NA inhibitor. This chapter use inhibitory activity based on information reported in the literature series of N-Substituted Oseltamivir Derivatives, using QSAR method calculate their quantum chemical informations based on the theory of DFT to build QSAR equation for N-Substituted Oseltamivir Derivatives structure and inhibition on NA in order to provide a theoretical basis for new Dual-inhibition molecules.Chapter IV: literature introduced Benzenesulfonamide Derivatives as Potent Anti-Influenza Hemagglutinin Inhibitors, this chapter based on the structure and inhibitory datas with HA in the paper. Using QSAR method calculate their quantum chemical informations based on the theory of DFT to build QSAR equation for Benzenesulfonamide Derivatives structure and inhibition on HA in order to provide a theoretical basis for new Dual-inhibition molecules.Chapter V: according to Chapters III and IV of the QSAR equation, combined with the structural characteristics of the active center of NA and HA to design new anti-influenza virus drug molecules with dual-inhibition. Using DFT theory calculate quantum chemical structural information for these new design molecule, theoretical predictions on them some have Dual-inhibition however some are poor. Synthesis the structural informations of the design have provide theoretical guidance for the further design drug molecules of high inhibitory activity against influenza virus with dual-inhibition.