This complete study - from rational design to validation by X-ray crystallography allowed us to discover two sub-nanomolar hAChE inhibitors (430 and 530 pM) grafted with an easily derivatized linker directed toward the AChE peripheral site. The crystal structure of mouse AChE in complex with compound 4 was solved and confirms the favorable position of the triazole in the active site gorge, paving the way for a new class of bifunctional ligands.
Ronco C, Carletti E, Colletier JP, Weik M, Nachon F, Jean L, Renard PY (2012) Huprine derivatives as sub-nanomolar human acetylcholinesterase inhibitors: from rational design to validation by X-ray crystallography ChemMedChem7: 400-5
Ronco C, Carletti E, Colletier JP, Weik M, Nachon F, Jean L, Renard PY (2012) ChemMedChem7: 400-5