3-Amidoquinuclidine derivatives: synthesis of compounds and inhibition of butyrylcholinesterase.
The synthesis of racemic and enantiomerically pure 3-butanamidoquinuclidines ((+/-)-Bu, (R)-Bu and (S)-Bu), (1-3) and 3-benzamidoquinuclidines ((+/-)-Bz, (R)-Bz, and (S)-Bz), (4-6) is described. The N-quaternary derivatives, N-benzyl-3-butanamidoquinuclidinium bromides ((+/-)-BnlBu, (R)-BnlBu and (S)-BnlBu), (7-9) and N-benzyl-3-benzamidoquinuclidinium bromides ((+/-)-BnlBz, (R)-BnlBz and (S)-BnlBz), (10-12) were subsequently synthesized. The interaction of the four enantiomerically pure quaternary derivatives with horse serum butyrylcholinesterase (BChE) was tested. All tested compounds inhibited the enzyme. The best inhibitior of the enzyme was (S)-BnlBz with a K(i) = 3.7 microM. The inhibitor potency decreases in order (S)-BnlBz > (R)-BnlBz >> (R)-BnlBu > (S)-BnlBu.
Odzak
Renata
R
Laboratory of Organic Chemistry, Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102A, HR-10 000 Zagreb, Croatia. rodzak@chem.pmf.hr
Tomić
Srdanka
S
D002091:Butyrylcholinesterase / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D011812:Quinuclidines / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D011812:Quinuclidines; D002091:Butyrylcholinesterase