title: Pharmacophore-based design, synthesis, and biological evaluation of novel chloro-pyridazine piperazines as human rhinovirus (HRV-3) inhibitors.
abstract: A series of chloro-pyridazine piperazines were developed based on the structure of human rhinovirus (HRV) capsid-binding inhibitors with proven activity using a pharmacophore model. A preliminary evaluation demonstrated potent activity against HRV-3 with low cytotoxicity. A docking analysis indicated that 8a could fit into, and form tight interactions (e.g., H-bonds, σ-π effect) with the active site in VP1.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Wang
authors.forename: Junhai
authors.initials: J
authors.lastname: Xiao
authors.forename: Dapeng
authors.initials: D
authors.lastname: Gao
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Zehui
authors.initials: Z
authors.lastname: Gong
authors.forename: Tinmin
authors.initials: T
authors.lastname: Sun
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D010879:Piperazines; D011724:Pyridazines; D014764:Viral Proteins; C062482:pyridazine