119th General Meeting of the KCS

Type Poster Presentation
Area 의약화학
Room No. 포스터발표장
Time 4월 20일 (목요일) 11:00~12:30
Code MEDI.P-460
Subject Novel Enterovirus Inhibitory Activity of 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo [4,3-a]pyrimidin-5(4H)-one analogs with C8-tert-butyl Group
Authors BISWAS BISHYAJIT KUMAR, 정영식1,*
과학기술연합대학원대학교(UST) 의약 및 약품화학, Korea
1한국화학연구원 신물질연구단, Korea
Abstract A series of 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e]triazolo[4,3-a]pyrimidin-5(4H)-one analogs (A), were prepared and tested for their inhibitory activity against representative enteroviruses. The activities were tested against Coxsackie Virus B1 (Cox B1), Coxsackie Virus B3 (Cox B3), Poliovirus 3 (PV3), Human Rhinovirus 14 (HRV14), Human Rhinovirus 21 (HRV21) and Human Rhinovirus 71 (HRV71). The C8-tert-butyl group in these derivatives was found to be crucial for the activity of these compounds against these enteroviruses. Compound 5 as a racemic mixture showed single digit micro molar activity (1.6 - 8.85 micromoles) in the whole spectrum of viruses screened. Substitution on phenyl ring at N4 position were tolerated, especially at ortho and para positions, among which compound 22 (p-methyl) and 29 (p-methoxy) being less cytotoxic, showed better selectivity indices against HRV14, HRV21 and HRV71 (selective index value range 4.6 - 12.2) compared to compound 5. In general phenyl substitutions were more tolerated in PV3 and HRV’s compared to Coxsackie strains & showed improved cytotoxicity in rhinoviruses. Metabolic stability of the compounds evaluated experimentally which shows them to be promising for further development. The chiral separation of compound 5 resulted compound with much better activity profile than the racemic form 5. The present study resulted in discovery of thienotriazolopyrimidinones as a novel skeleton as replication inhibitor of enterovirus.
E-mail biswas@krict.re.kr