title: Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors.
abstract: A novel series of HCV replication inhibitors based on a pyrido[3,2-d]pyrimidine core were optimized for pharmacokinetics (PK) in rats. Several associations between physicochemical properties and PK were identified and exploited to guide the design of compounds. In addition, a simple new metric that may aid in the prediction of bioavailability for compounds with higher polar surface area is described (3*HBD-cLogP).
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Lazerwith
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Gina
authors.initials: G
authors.lastname: Bahador
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Eda
authors.initials: E
authors.lastname: Canales
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Lee
authors.initials: L
authors.lastname: Chong
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Clarke
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Doerffler
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Eisenberg
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Hayes
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Lu
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Matles
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Mertzman
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mitchell
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Philip
authors.initials: P
authors.lastname: Morganelli
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Murray
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: Robinson
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Strickley
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Tessler
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Tirunagari
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Xubin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Medicinal Chemistry, Drug Metabolism, Biology, and Formulation and Process Development, Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: William J
authors.initials: WJ
authors.lastname: Watkins
keywords: 3*HBD-cLogP; HCV inhibitors; Pharmacokinetics; pyrido[3,2-d]pyrimidine core