2. Academic Validation
  3. Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E₂ synthase-1 inhibitors

Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E₂ synthase-1 inhibitors

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):285-8. doi: 10.1016/j.bmcl.2011.11.015.
Tomoya Shiro 1,  Hirotada Takahashi,  Keisuke Kakiguchi,  Yoshifumi Inoue,  Keiki Masuda,  Hidetaka Nagata,  Masanori Tobe
Affiliations

Affiliation

  • 1 Drug Research Division, Dainippon Sumitomo Pharma. Co. Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
PMID: 22137787 DOI: 10.1016/j.bmcl.2011.11.015
Abstract

The imidazoquinoline derivative 1 was found as a novel mPGES-1 inhibitor. Optimization of 1 led to the identification of the 2-chlorophenyl group at the C(2)-position and the Quinolone structure at the C(4)-position. Compound 33, the most potent synthesized compound, showed excellent mPGES-1 inhibition (IC(50)=9.1nM) with high selectivity (>1000-fold) over both COX-1 and COX-2.

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