title: Synthesis and biological evaluation of triazolothienopyrimidine derivatives as novel HIV-1 replication inhibitors.
abstract: We identified a novel class of triazolothienopyrimidine (TTPM) compounds as potent HIV-1 replication inhibitors during a high-throughput screening campaign that evaluated more than 200,000 compounds using a cell-based full replication assay. Herein, we report the optimization of the antiviral activity in a cell-based assay system leading to the discovery of aryl-substituted TTPM derivatives (38, 44, and 45), which exhibited significant inhibition of HIV-1 replication with acceptable safety margins. These novel and potent TTPMs could serve as leads for further development.
authors.affiliation: Medicinal Chemistry 2, Institut Pasteur Korea, Sampyeong-dong 696, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.
authors.forename: Junwon
authors.initials: J
authors.lastname: Kim
authors.forename: Jeongjin
authors.initials: J
authors.lastname: Kwon
authors.forename: Doohyun
authors.initials: D
authors.lastname: Lee
authors.forename: Suyeon
authors.initials: S
authors.lastname: Jo
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Park
authors.forename: Jihyun
authors.initials: J
authors.lastname: Choi
authors.forename: Eunjung
authors.initials: E
authors.lastname: Park
authors.forename: Jong Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Yoonae
authors.initials: Y
authors.lastname: Ko
authors.forename: Inhee
authors.initials: I
authors.lastname: Choi
authors.forename: Moon Kyeong
authors.initials: MK
authors.lastname: Ju
authors.forename: JiYe
authors.initials: J
authors.lastname: Ahn
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Han
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Kim
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cechetto
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Nam
authors.forename: Sujin
authors.initials: S
authors.lastname: Ahn
authors.forename: Peter
authors.initials: P
authors.lastname: Sommer
authors.forename: Michel
authors.initials: M
authors.lastname: Liuzzi
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; D014230:Triazoles; C476003:thienopyrimidine