title: Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors.
abstract: Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R(1), R(2) or R(3) positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC(50)), PK parameters in all species studied, and cross genotype activity.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Rd., Kenilworth, NJ 07033, USA. vinay.girijavallabhan@spcorp.com
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Girijavallabhan
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez
authors.forename: Frank
authors.initials: F
authors.lastname: Bennett
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Stephen
authors.initials: S
authors.lastname: Gavalas
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Huang
authors.forename: Seong-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Aneta
authors.initials: A
authors.lastname: Kosinski
authors.forename: Patrick
authors.initials: P
authors.lastname: Pinto
authors.forename: Razia
authors.initials: R
authors.lastname: Rizvi
authors.forename: Randall
authors.initials: R
authors.lastname: Rossman
authors.forename: Bandarpalle
authors.initials: B
authors.lastname: Shankar
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.forename: Francisco
authors.initials: F
authors.lastname: Velazquez
authors.forename: Srikanth
authors.initials: S
authors.lastname: Venkatraman
authors.forename: Vishal A
authors.initials: VA
authors.lastname: Verma
authors.forename: Joseph
authors.initials: J
authors.lastname: Kozlowski
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Cecil D
authors.initials: CD
authors.lastname: Kwong
authors.forename: Namita
authors.initials: N
authors.lastname: Bansal
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Clark
authors.forename: Anita T
authors.initials: AT
authors.lastname: Fowler
authors.forename: Hollis S
authors.initials: HS
authors.lastname: Kezar
authors.forename: Jacob
authors.initials: J
authors.lastname: Valiyaveettil
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reynolds
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Maddry
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ananthan
authors.forename: John A
authors.initials: JA
authors.lastname: Secrist
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Chase
authors.forename: Stephanie
authors.initials: S
authors.lastname: Curry
authors.forename: Hsueh-Cheng
authors.initials: HC
authors.lastname: Huang
authors.forename: Xiao
authors.initials: X
authors.lastname: Tong
authors.forename: F George
authors.initials: FG
authors.lastname: Njoroge
authors.forename: Ashok
authors.initials: A
authors.lastname: Arasappan
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011743:Pyrimidines; D013844:Thiazoles