2. Academic Validation
  3. 5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor

5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)--a potent FLAP inhibitor

  • Bioorg Med Chem Lett. 2010 Jan 1;20(1):213-7. doi: 10.1016/j.bmcl.2009.10.131.
Nicholas Stock 1,  Christopher Baccei,  Gretchen Bain,  Alex Broadhead,  Charles Chapman,  Janice Darlington,  Christopher King,  Catherine Lee,  Yiwei Li,  Daniel S Lorrain,  Pat Prodanovich,  Haojing Rong,  Angelina Santini,  Jasmine Zunic,  Jilly F Evans,  John H Hutchinson,  Peppi Prasit
Affiliations

Affiliation

  • 1 Amira Pharmaceuticals, 9535 Waples St., Suite 100, San Diego, CA 92121, USA. [email protected]
PMID: 19914828 DOI: 10.1016/j.bmcl.2009.10.131
Abstract

A series of potent 5-lipoxygenase-activating protein (FLAP) inhibitors are herein described. SAR studies focused on the discovery of novel alicyclic moieties appended to an indole core to optimize potency, physical properties and off-target activities. Subsequent SAR on the N-benzyl substituent of the indole led to the discovery of compound 39 (AM679) which showed potent inhibition of leukotrienes in human blood and in a rodent bronchoalvelolar lavage (BAL) challenge model.

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