2. Academic Validation
  3. Heteroaromatic-aminomethyl quinolones: potent and selective iNOS inhibitors

Heteroaromatic-aminomethyl quinolones: potent and selective iNOS inhibitors

  • Bioorg Med Chem Lett. 2012 Jan 15;22(2):1237-41. doi: 10.1016/j.bmcl.2011.11.073.
Sergio G Durón 1,  Andrew Lindstrom,  Céline Bonnefous,  Hui Zhang,  Xiaohong Chen,  Kent T Symons,  Marciano Sablad,  Natasha Rozenkrants,  Yan Zhang,  Li Wang,  Nahid Yazdani,  Andrew K Shiau,  Stewart A Noble,  Peter Rix,  Tadimeti S Rao,  Christian A Hassig,  Nicholas D Smith
Affiliations

Affiliation

  • 1 Afraxis, La Jolla, CA 92037, United States.
PMID: 22182498 DOI: 10.1016/j.bmcl.2011.11.073
Abstract

The overproduction of nitric oxide during the biological response to inflammation by the nitric oxide synthase (NOS) Enzymes have been implicated in the pathology of many diseases. By removal of the amide core from uHTS-derived Quinolone 4, a new series highly potent heteroaromatic-aminomethyl Quinolone iNOS inhibitors 8 were identified. SAR studies led to identification of piperazine 22 and pyrimidine 32, both of which reduced plasma nitrates following oral dosing in a mouse lipopolysaccharide challenge assay.

Figures