TY - JOUR
T1 - SAR studies of piperidine-based analogues of cocaine. Part 3
T2 - Oxadiazoles
AU - Petukhov, Pavel A.
AU - Zhang, Mei
AU - Johnson, Kenneth J.
AU - Tella, Srihari R.
AU - Kozikowski, Alan P.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001/8/20
Y1 - 2001/8/20
N2 - The synthesis of novel 4β-aryl-1-methyl-3α-(3-substituted-1,2,4-oxadiazol-5-yl) piperidines, bioisosteres of ester (+)-1, is described. The synthesized oxadiazoles were evaluated for their affinity to the DAT and their ability to inhibit monoamine reuptake at the DAT, NET, and 5HTT. The results show that affinity to the DAT and ability to inhibit the reuptake at the DAT, NET, and 5HTT is a function of the size of the substituent in the oxadiazole ring. (+)-(3R,4S)-4β-(4-Chlorophenyl)-1-methyl-3α-(3-methyl-1,2,4- oxadiazol-5-yl)piperidine [(+)-2a], which is structurally and pharmacologically most similar to the ester (+)-1 in this series, showed at least a 2-fold longer duration of action when compared to ester (+)-1.
AB - The synthesis of novel 4β-aryl-1-methyl-3α-(3-substituted-1,2,4-oxadiazol-5-yl) piperidines, bioisosteres of ester (+)-1, is described. The synthesized oxadiazoles were evaluated for their affinity to the DAT and their ability to inhibit monoamine reuptake at the DAT, NET, and 5HTT. The results show that affinity to the DAT and ability to inhibit the reuptake at the DAT, NET, and 5HTT is a function of the size of the substituent in the oxadiazole ring. (+)-(3R,4S)-4β-(4-Chlorophenyl)-1-methyl-3α-(3-methyl-1,2,4- oxadiazol-5-yl)piperidine [(+)-2a], which is structurally and pharmacologically most similar to the ester (+)-1 in this series, showed at least a 2-fold longer duration of action when compared to ester (+)-1.
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U2 - 10.1016/S0960-894X(01)00379-1
DO - 10.1016/S0960-894X(01)00379-1
M3 - Article
C2 - 11514143
AN - SCOPUS:0035921116
VL - 11
SP - 2079
EP - 2083
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 16
ER -