title: Novel fused pyrimidine and isoquinoline derivatives as potent HIV-1 NNRTIs: a patent evaluation of WO2016105532A1, WO2016105534A1 and WO2016105564A1.
abstract: In the three patent applications, the impact of changing the pyrimidine core of the rilpivirine (RPV) to a variety of alternative fused cores was explored, culminating in the identification of a series of conformationally restricted compounds with comparable potencies against WT and mutant HIV-1 strains with those of efavirenz (EFV) and RPV, and higher security in the Human Ether-a-go-go-Related Gene (hERG) assay. Areas covered: The present review provides a fused pyrimidine and isoquinoline derivatives as potent HIV-1 NNRTIs, and highlights the conformational restriction strategies in the development of NNRTIs. Expert opinion: The molecular docking analysis of the newly synthesized compounds maintain the classical horseshoe conformation and shares similar binding mode with RPV. The conformational restriction strategies have greatly accelerated the optimization of the DAPY NNRTIs and contribute to finding new chemical entities (NCEs) with favorable druggability.
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Shandong , PR 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 , Shandong , PR China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Huo
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Shandong , PR China.
authors.forename: Gaochan
authors.initials: G
authors.lastname: Wu
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Shandong , PR China.
authors.forename: Jiabao
authors.initials: J
authors.lastname: Xu
authors.affiliation: a Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Shandong , PR 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 , Shandong , PR 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 / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D010330:Patents as Topic; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D007546:Isoquinolines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1; NNRTI; diarylpyrimidine; fused pyrimidine; isoquinoline