78325-26-5Relevant articles and documents
Halogenated mazindol analogs as potential inhibitors of the cocaine binding site at the dopamine transporter
Houlihan, William J.,Boja, John W.,Parrino, Vincent A.,Kopajtic, Theresa A.,Kuhar, Michael J.
, p. 4935 - 4941 (2007/10/03)
A series of halogenated (F, Cl, Br, I), pyrimido and diazepino homologs of mazindol were prepared and evaluated for their ability to displace [3H]WIN 35,428 binding and to inhibit uptake of [3H]dopamine (DA) in rat striatal tissue. All of the compounds except for the 2'-chloro (6) and 2'- bromo (16) analogs of mazindol displaced [3H]WIN 35,428 binding and inhibited [3H]DA uptake more effectively than (R)-cocaine. Structure- activity studies indicated that best inhibition of [3H]WIN 35,428 binding occurred in the imidazo series with compounds containing one or two Cl or Br atoms in the 3'- or 4'-position of the free phenyl group. Replacement of the imidazo ring by a pyrimido or diazepino ring enhanced binding inhibition. The most potent inhibitors of [3H]WIN 35,428 binding and [3H]DA uptake were 6- (3'-chlorophenyl)-2,3,4,6-tetrahydropyrimido[2,1-α]isoindol-6-ol (23; IC50 1.0 nM; 8x mazindol) and 7-(3',4'-dichlorophenyl)-2,3,4,5-tetrahydro-7H- diazepino[2,1-α]isoindol-7-ol (28; IC50 0.26 nM; 32x mazindol), respectively. No significant differences was found between binding and uptake inhibition. Mazindol and the pyrimido and diazepino homologs 24 and 27 showed a selectivity for the DA uptake over the serotonin (5-HT) uptake site of 5-, 250-, and 465-fold, respectively, and displayed weak or no affinity for a variety of neurotransmitter receptor sites.
