Synthesis and structure activity relationships (SAR) of a new class of potent and selective butyrylcholinesterase inhibitors.
Reported here is the synthesis and SAR of novel group of highly potent and selective inhibitors of human plasma butyrylcholinesterase (BuChE; EC 3.1.1.8). The design is based on the discovery that isosorbide 2-esters are hydrolysed by BuChE at exceptionally rapid rates. Two families of carbamates were synthesised in which the vulnerable 2-ester was replaced with a carbamate or reversed carabamate. Several compounds in one of the families are among the most potent and selective BuChE inhibitors reported.
Gaynor
Joanne M
JM
School of Science, Athlone I.T. Co Westmeath, Ireland. jgaynor@ait.ie <jgaynor@ait.ie>
Dillon
Gerald P
GP
Reidy
Sean
S
Gilmer
John F
JF
D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D002091:Butyrylcholinesterase