Premium
2′‐Substituted analogs of cocaine: synthesis and dopamine transporter binding potencies
Author(s) -
ElMoselhy Tarek F.,
Avor Kwasi S.,
Basmadjian Garo P.
Publication year - 2001
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200109)334:8/9<275::aid-ardp275>3.0.co;2-b
Subject(s) - chemistry , radioligand , dopamine transporter , stereochemistry , hydrolysis , dopamine , chloride , benzene , medicinal chemistry , binding site , transporter , organic chemistry , biochemistry , biology , neuroscience , gene
A series of 2′‐substituted cocaine analogs (4‐8) was prepared and evaluated in an in vitro dopamine transporter (DAT) binding assay. Compounds 4‐7 were prepared by esterifying the 3β‐hydroxyl group of ecgonine methyl ester (3) using the appropriate acid chloride in the presence of Et 3 N and benzene. Compound 3 was obtained from cocaine (1) by hydrolysis using 1N HCl to afford ecgonine . HCl which was subjected to acid catalyzed esterification using methanol saturated with HCl gas. Compound 8 was obtained by hydrogenation of 7 using H 2 /Pd‐C. The IC 50 values were calculated from displacement experiment of the radioligand [ 3 H]WIN‐35,428 (2) . 2′‐Aminococaine (8) showed high binding affinity to the DAT (14‐ and 1.3‐fold more active than cocaine and the radioligand 2 , respectively). These results, along with previous results, emphasize the importance of a hydrogen‐bond donor group at the 2′‐position of cocaine to enhance binding affinity to the DAT.