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Concluded Synthesis

L-684,414: g-secretase Inhibitor

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L-684,414 (3) is a potent inhibitor of g-secretase (IC 50 = 181 nM) and is of potential therapeutic benefit in the treatment of Alzheimer’s disease and other neurological disorders.

L-684,414 is a novel inhibitor of AbPP-g-secretase activity, with a similar potency for inhibition of Ab(42) and Ab(40) peptides. L-684,414 contains a hydroxyethylene dipeptide isostere that should serve as a transition state analogue mimic to direct the inhibitor to the active site of an aspartyl protease target.


  1. "Allyltrichlorostannane Additions to alpha-Aminoaldehydes. Application to the Total Synthesis of the Aspartyl Protease Inhibitors L-682,679, L684,414, L-685,434, and L-685,458". Dias, L.C.; Diaz, G.; Ferreira, A.A.; Meira, P.R.R.; Ferreira, E. Synthesis 2003, 4, 603-622.

  2. “Short Total Synthesis of Aspartyl Protease Inhibitors L-685,434, L-682,679 and L-685,458”. Dias, L.C.; Ferreira, A.A.; Diaz, G. Synlett 2002, 1845-1849.


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