Publications [#330226] of Michael J. Therien

Papers Published

1. Macdonald, D; Brideau, C; Chan, CC; Falgueyret, J-P; Frenette, R; Guay, J; Hutchinson, JH; Perrier, H; Prasit, P; Riendeau, D; Tagari, P; Thérien, M; Young, RN; Girard, Y, Substituted 2,2-bisaryl-bicycloheptanes as novel and potent inhibitors of 5-lipoxygenase activating protein., Bioorganic & medicinal chemistry letters, vol. 18 no. 6 (March, 2008), pp. 2023-2027 [doi]
   (last updated on 2026/01/15)

   Abstract:
   The discovery and SAR of a novel series of substituted 2,2-bisaryl-bicycloheptane inhibitors of 5-lipoxygenase activating protein (FLAP) are herein described. SAR studies have shown that 2,5-substitution on the exo-aryl group is optimal for potency. The most potent compounds in this series have an ortho-nitrogen aryl linked with a methyleneoxy as the 5-substituent and a polar group such as a urethane as the 2-substituent. One of the most potent compounds identified is the 5-benzothiazolymethoxy-2-pyridinylcarbamate derivative 2 (FLAP IC(50)=2.8 nM) which blocks 89% of ragweed induced urinary LTE(4) production in dogs (at an I.V. dose of 2.5 microg/kg/min). This compound inhibits calcium ionophore stimulated LTB(4) production in both human polymorphonuclear (PMN) leukocytes and human whole blood (IC(50)=2.0 and 33 nM, respectively).