192648-66-1Relevant academic research and scientific papers
Synthesis and dopamine transporter binding of 2'-substituted cocaine analogs
El-Moselhy, Tarek F.,Avor, Kwasi S.,Basmadjian, Garo P.
, p. 50 - 57 (2007/10/03)
A series of 2'-substituted cocaine analogs (4-8) was synthesized and evaluated in an in vitro dopamine transporter (DAT) system. 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 NEt3 and benzene. Compound 3 was obtained from cocaine (1) by hydrolysis using lN HCl to afford ecgonine HCl which was subjected to acid catalyzed esterification using MeOH saturated with HCl gas. Compound 8 was obtained from 5 by selective trans- esterification with MeOH and HCl gas. The binding affinities of these compounds were determined at DAT for the displacement of [3H]WIN-35428 (2). The 2'-substituted acetoxy and hydroxy analogs exhibited high binding potency for the DAT compared to cocaine (3.5- and 10-fold respectively).
Synthesis and ligand binding studies of 4'-iodobenzyl esters of tropanes and piperidines at the dopamine transporter
Singh, Satendra,Basmadjian, Garo P.,Avor, Kwasi S.,Pouw, Buddy,Seale, Thomas W.
, p. 2474 - 2481 (2007/10/03)
Four analogs and two homologs of cocaine, designed as potent cocaine antagonists, were synthesized. The S(N)2 reaction between ecgonine methyl ester (13) or appropriately substituted piperidinol (19, 21) and appropriately substituted 4-indobenzoyl chloride gave 4-indobenzoyl esters of tropane and piperidines (5-8). 2'-Hydroxycocaine (9) was obtained from 2'- acetoxycocaine (12) by selective transesterification with MeOH saturated with dry HCl gas. 2'-Acetoxycocaine (12) was synthesized from acetylsalicyloyl chloride (23) and ecgonine methyl ester (13). The binding affinities of these compounds were determined at the dopamine transporter for the displacement of ([3H]WIN-35428. An iodo group substitution at the 4'-position of cocaine decreased dopamine transporter binding potency, while a hydroxy or acetoxy group at the 2'-position exhibited increased binding potency for the dopamine transporter compared to cocaine (10- and 3.58-fold, respectively). 2'- Hydroxylation also enhanced the binding potency of 4'-iodococaine (5) by 10- fold. Replacement of the tropane ring with piperidine led to poor binding affinities.
