title: Design and syntheses of 1,6-naphthalene derivatives as selective HCMV protease inhibitors.
abstract: Through high throughput screening of various libraries, substituted styryl naphthalene 6 was identified as an HCMV protease inhibitor. Optimization of various regions of the lead molecule using parallel synthesis resulted in 1,6-substituted naphthalenes 19d-i. These compounds displayed good potency and were selective over elastase, trypsin, and chymotrypsin. The optimization approach on lead compound 6 in three different regions of the molecule using parallel solution-phase synthesis and the corresponding SAR are discussed in detail.
authors.affiliation: Chemical and Screening Sciences and Infectious Diseases,Wyeth Research, Pearl River, NY 10965, USA. gopalsa@wyeth.com
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Kitae
authors.initials: K
authors.lastname: Lim
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
authors.forename: Boris
authors.initials: B
authors.lastname: Mitsner
authors.forename: Antonia
authors.initials: A
authors.lastname: Nikitenko
authors.forename: Janis
authors.initials: J
authors.lastname: Upeslacis
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Mansour
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Olson
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: Bebernitz
authors.forename: Diane
authors.initials: D
authors.lastname: Grinberg
authors.forename: Boris
authors.initials: B
authors.lastname: Feld
authors.forename: Franklin J
authors.initials: FJ
authors.lastname: Moy
authors.forename: John
authors.initials: J
authors.lastname: O'Connell
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D003587:Cytomegalovirus / Q000737:chemistry*; D016208:Databases, Factual; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C485102:C,C,C-trifluoro-N-(5-(2-pyridin-2-ylvinyl)naphthalen-2-yl)methanesulfonamide; D009281:Naphthalenes; D011480:Protease Inhibitors; D013449:Sulfonamides; D015081:2-Naphthylamine; D012697:Serine Endopeptidases; C071910:assemblin