title: Novel diaryltriazines with a picolinonitrile moiety as potent HIV-1 RT inhibitors: a patent evaluation of WO2016059647(A2).
abstract: Diaryltriazine derivatives, which are structurally related to diarylpyrimidines, are a representative class of HIV-1 reverse transcriptase inhibitors with remarkable antiviral activities against wild-type and several mutant strains of HIV-1. A series of novel diaryltriazines with a picolinonitrile moiety was reported as potent HIV-1 RT inhibitors in the patent WO2016059647(A2). Two representative compounds 5e (hydrochloride) and 6e (hydrochloride) exhibited outstanding activities against various HIV-1 strains in cell-based assays, which were superior to those of AZT. Moreover, modeling simulation study is performed and discussed in details, providing deep insights and valuable information to explain the excellent antiviral potency of 6e. Finally, several cases to improve anti-drug-resistance profiles by targeting highly conserved residues in HIV-1 RT are herein preliminarily summarized.
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Huang
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Kang
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Wanzhuo
authors.initials: W
authors.lastname: Li
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.affiliation: a Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , Shandong , P. R. China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010330:Patents as Topic; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D014227:Triazines; D015215:Zidovudine
keywords: Diaryltriazine; HIV-1 RT inhibitors; highly conserved residues; modeling simulation; picolinonitrile