Achieving structural diversity using the perpendicular conformation of alpha-substituted phenylcyclopropanes to mimic the bioactive conformation of ortho-substituted …

…, DL Cheney, RS Alexander, AM Smallwood…

Index: Qiao, Jennifer X.; Cheney, Daniel L.; Alexander, Richard S.; Smallwood, Angela M.; King, Sarah R.; He, Kan; Rendina, Alan R.; Luettgen, Joseph M.; Knabb, Robert M.; Wexler, Ruth R.; Lam, Patrick Y.S. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 14 p. 4118 - 4123

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Citation Number: 21

Abstract

Ortho-substituted biphenyl moieties are widely used in drug design. We herein report a successful use of the perpendicular conformation of the alpha-substituted phenylcyclopropyl groups to mimic the aplanar, biologically active conformation of the ortho-substituted biphenyl moieties to achieve structural diversity. This is exemplified by the design and synthesis of a series of highly potent pyrazole bicyclic-based Factor Xa (FXa) inhibitors ...