title: Synthesis and antiviral activity of novel 1,3,4-thiadiazine derivatives.
abstract: A series of novel 1,3,4-thiadiazine derivatives were synthesized via chemical optimization on phthiobuzone. Their anti-herpes simplex virus (HSV) activities in vitro were also tested. Several compounds exhibited more highly potent anti-HSV activity and much higher selectivity index (SI) values than those of phthiobuzone. The most potent anti-HSV compound was 4f, which showed marked inhibition against HSV-1 (IC₅₀=77.04 µg/ml) and HSV-2 (IC₅₀=30.00 µg/ml). Meanwhile it had low cytotoxicity (CC₅₀=1000.00 µg/ml), resulting in high (SI(HSV-1)=12.98, SI(HSV-2)=33.33, respectively). Furthermore, a computational study for prediction of absorption, distribution, metabolism, excretion (ADME) properties of compound 4f was performed by determination of topological polar surface area, absorption and Lipinski parameters.
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine (Ministry of Education), Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.forename: Ziming
authors.initials: Z
authors.lastname: Feng
authors.forename: Jianshuang
authors.initials: J
authors.lastname: Jiang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiandao
authors.initials: X
authors.lastname: Pan
authors.forename: Peicheng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D013829:Thiadiazines