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Discovery of AZD2716: A Novel Secreted Phospholipase A₂ (sPLA₂) Inhibitor for the Treatment of Coronary Artery Disease.

ABSTRACT: Expedited structure-based optimization of the initial fragment hit 1 led to the design of (R)-7 (AZD2716) a novel, potent secreted phospholipase A₂ (sPLA₂) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7 was selected as a clinical candidate for the treatment of coronary artery disease.

SUBMITTER: Giordanetto F

PROVIDER: S-EPMC5066155 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Discovery of AZD2716: A Novel Secreted Phospholipase A2 (sPLA2) Inhibitor for the Treatment of Coronary Artery Disease.

Giordanetto Fabrizio F Pettersen Daniel D Starke Ingemar I Nordberg Peter P Dahlström Mikael M Knerr Laurent L Selmi Nidhal N Rosengren Birgitta B Larsson Lars-Olof LO Sandmark Jenny J Castaldo Marie M Dekker Niek N Karlsson Ulla U Hurt-Camejo Eva E

ACS medicinal chemistry letters 20160809 10

Expedited structure-based optimization of the initial fragment hit 1 led to the design of (R)-7 (AZD2716) a novel, potent secreted phospholipase A2 (sPLA2) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7 was selected as a clinical candidate for the treatment of coronary artery disease. ...[more]

PMID: 27774123

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