Lipase-catalysed synthesis of new acetylcholinesterase inhibitors: N-benzylpiperidine aminoacid derivatives.
New acetylcholinesterase inhibitors were synthetized via a lipase-mediated regioselective amidation using Candida antarctica lipase B as a biocatalyst in the key step. The new compounds have two different structural fragments: a N-benzylpiperidine moiety to anchor the enzyme active site and a dicarboxylic aminoacid to act as a biological carrier. Some analogues of N-benzylpiperazine were also synthesised and studied but they did not display AChE inhibitor activity. A preliminary structure activity relationship study was performed employing some computational techniques as similarity indices and electrostatic potential maps.
Martínez
A
A
Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
Lanot
C
C
Perez
C
C
Castro
A
A
López-Serrano
P
P
Conde
S
S
D000110:Acetylcholinesterase / Q000187:drug effects*; D002175:Candida / Q000201:enzymology; D002384:Catalysis; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055672:Static Electricity
D002800:Cholinesterase Inhibitors; D010880:Piperidines; D008049:Lipase; D000110:Acetylcholinesterase