title: Synthesis and biological evaluation of novel HIV-1 protease inhibitors using tertiary amine as P2-ligands.
abstract: A series of tertiary amine derivatives exhibiting potent HIV-1 protease inhibiting properties were identified. These novel inhibitors were designed based on the structure of Darunavir with modification on the P2 and P2' position. This effort led to discovery of 35e and 38e, which exhibited excellent HIV-1 protease inhibition with IC50 values of 15 nM and 64 nM, respectively.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Bai
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Ju-Xian
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Hebei General Hospital, Hebei, Shijiazhuang 050051, PR China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: wyc9999@gmail.com.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Wang
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D008024:Ligands; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D017320:HIV Protease Inhibitors; D008024:Ligands; D016333:HIV Protease
keywords: Darunavir; HAART; HIV-1 protease; Inhibitors