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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).

SUBMITTER: Lazerwith SE 

PROVIDER: S-EPMC4018142 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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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). ...[more]

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