US EPA

1165824 

Journal Article 

2 '-substituted analogs of cocaine: synthesis and dopamine transporter binding potencies 

El-Moselhy, TF; Avor, KS; Basmadjian, GP 

2001 

Yes 

Archiv der Pharmazie
ISSN: 0365-6233
EISSN: 1521-4184 

334 

8-9 

275-278 

English 

11688137 

10.1002/1521-4184(200109)334:8/9<275::aid-ardp275>3.0.co;2-b 

WOS:000171615000003 

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0034740519&doi=10.1002%2f1521-4184%28200109%29334%3a8%2f9%3c275%3a%3aAID-ARDP275%3e3.0.CO%3b2-B&partnerID=40&md5=847fb2a1831b3c663dfba91fa49e0b33
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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 3 beta-hydroxyl group of ecgonine methyl ester (3) using the appropriate acid chloride in the presence of Et3N 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 H2/Pd-C. The IC50 values were calculated from displacement experiment of the radioligand [3H]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. 

cocaine analogs; substituted cocaines; cocaine antagonists; dopaminergic system