Synthesis and Antiviral Activities of Some 2,4,6-Trisubstituted 1,3,5-Triazines

• Published in: Chemical & pharmaceutical bulletin Vol. 62; no. 10; pp. 1032 - 1040
• Main Authors: Mibu, Nobuko, Yokomizo, Kazumi, Koga, Airi, Honda, Miyuki, Mizokami, Kou, Fujii, Hiroyuki, Ota, Norimasa, Yuzuriha, Ai, Ishimaru, Kanji, Zhou, Jianrong, Miyata, Takeshi, Sumoto, Kunihiro
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.10.2014; Pharmaceutical Society of Japan; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: 1,3,5-triazine; Animals; anti-herpes simplex virus type 1; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; C3 symmetry; Cell Survival - drug effects; Cercopithecus aethiops; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; CS symmetry; cytotoxic activity; Herpesvirus 1, Human - drug effects; Humans; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; plaque reduction assay; Science & Technology; Structure-Activity Relationship; Triazines - chemical synthesis; Triazines - chemistry; Triazines - pharmacology; Vero Cells; Cs symmetry; anti-herpes simplex virus type 1; C-3 symmetry; COUPLING REAGENTS; 1,3,5-triazine; cytotoxic activity; plaque reduction assay; PROTEINS; DERIVATIVES
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c14-00421

We describe the synthesis and results of biological evaluation of newly designed 2,4,6-trisubstituted symmetrical 1,3,5-triazine (TAZ) derivatives. Among the tested trisubstituted TAZ derivatives, some CS-symmetrical alkoxy-amino-substituted TAZ derivatives, including 7ggp and 6dpp, showed significant antiviral activity against herpes simplex virus type 1 (HSV-1). The compound with the highest level of antiviral activity was C3-symmetrical trialkoxy-TAZ derivative 4bbb, which showed a considerably high selectivity index (IC50/EC50=256.6). The structure–activity relationships for anti-HSV-1 activity of the tested 2,4,6-trisubstituted TAZ derivatives are also described.