141120-39-0Relevant articles and documents
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.
