Dutta A K, Xu C, Reith M E
Organix Inc., Woburn, Massachusetts 01801, USA.
J Med Chem. 1996 Feb 2;39(3):749-56. doi: 10.1021/jm9506581.
Several analogs of the potent dopamine (DA) transporter ligand 4-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-1-(3-phenylpropyl)piperidine, 1b, were made and biologically evaluated for their binding at the DA and serotonin (5HT) transporters in rat striatal membranes. Different alkyl chain lengths and substitutions were introduced in these molecules to generate an optimum activity and selectivity for the DA transporter. In general, unsubstituted and fluoro-substituted compounds were the most active and selective for the DA transporter. The compound 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, 9a, showed high potency and was the most selective for the DA transporter (5HT/DA = 49) in this series of compounds. Some of these novel analogs were found to be more selective in binding at the DA transporter than the original GBR 12909 molecule, 1-[2-]bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperidine.
制备了强效多巴胺（DA）转运体配体4-[2-[双（4-氟苯基）-甲氧基]乙基]-1-（3-苯基丙基）哌啶（1b）的几种类似物，并对其在大鼠纹状体膜中与DA和5-羟色胺（5HT）转运体的结合进行了生物学评估。在这些分子中引入不同的烷基链长度和取代基，以产生对DA转运体的最佳活性和选择性。一般来说，未取代和氟取代的化合物对DA转运体最具活性和选择性。化合物4-[2-（二苯基甲氧基）乙基]-1-苄基哌啶（9a）表现出高效力，并且在该系列化合物中对DA转运体的选择性最高（5HT/DA = 49）。发现这些新型类似物中的一些在与DA转运体结合方面比原始的GBR 12909分子1-[2-]双（4-氟苯基）甲氧基]乙基]-4-（3-苯基丙基）哌啶更具选择性。
