title: A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with improved metabolic stability.
abstract: Following the previous SAR of a novel dihydropyrimidinone scaffold as HIV-1 replication inhibitors a detailed study directed towards optimizing the metabolic stability of the ester functional group in the dihydropyrimidinone (DHPM) scaffold is described. Replacement of the ester moiety by thiazole ring significantly improved the metabolic stability while retaining antiviral activity against HIV-1 replication. These novel and potent DHPMs with bioisosteres could serve as advanced leads for further optimization.
authors.affiliation: Medicinal Chemistry Group, 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: Taedong
authors.initials: T
authors.lastname: Ok
authors.forename: Changmin
authors.initials: C
authors.lastname: Park
authors.forename: Wonyoung
authors.initials: W
authors.lastname: So
authors.forename: Mina
authors.initials: M
authors.lastname: Jo
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Minjung
authors.initials: M
authors.lastname: Seo
authors.forename: Doohyun
authors.initials: D
authors.lastname: Lee
authors.forename: Suyeon
authors.initials: S
authors.lastname: Jo
authors.forename: Yoonae
authors.initials: Y
authors.lastname: Ko
authors.forename: Inhee
authors.initials: I
authors.lastname: Choi
authors.forename: Youngsam
authors.initials: Y
authors.lastname: Park
authors.forename: Jaewan
authors.initials: J
authors.lastname: Yoon
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: Michel
authors.initials: M
authors.lastname: Liuzzi
authors.forename: Peter
authors.initials: P
authors.lastname: Sommer
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004355:Drug Stability; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D019829:Nevirapine / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D019829:Nevirapine; D054303:HIV Reverse Transcriptase