Chang A C, Burgess J P, Mascarella S W, Abraham P, Kuhar M J, Carroll F I
Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA.
J Med Chem. 1997 Apr 11;40(8):1247-51. doi: 10.1021/jm960703k.
2beta,3beta-Diphenyl-(5), 2alpha,3alpha-diphenyl-(6), and 2alpha,3beta-diphenyltropane (3) as well as 2,3-diphenyltrop-2-ene (4) were prepared in racemic form and assayed for inhibition of radioligand binding at the dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters. Among all three transporters, compounds 4-6 bound the DA transporter with the highest affinity. The 2beta,3beta-diphenyltropane (5) bound the DA transporter with an IC50 value (28 nM) almost identical to that of 3beta-phenyltropane-2beta-carboxylic acid methyl ester (WIN 35,065-2) and has much greater selectivity relative to binding to the serotonin transporter. A comparison of the radioligand data from this study to radioligand data obtained on other WIN 35,065-2 analogs suggests that hydrophobicity of the C-2 substituent of some analogs of the WIN 35,065-2 class may be an important contributing factor to binding at the DA transporter.
外消旋形式的2β,3β-二苯基-（5）、2α,3α-二苯基-（6）和2α,3β-二苯基托烷（3）以及2,3-二苯基托-2-烯（4）被制备出来，并测定了它们对多巴胺（DA）、5-羟色胺（5-HT）和去甲肾上腺素（NE）转运体放射性配体结合的抑制作用。在所有三种转运体中，化合物4 - 6与DA转运体的结合亲和力最高。2β,3β-二苯基托烷（5）与DA转运体结合的IC50值（28 nM）几乎与3β-苯基托烷-2β-羧酸甲酯（WIN 35,065 - 2）相同，并且相对于与5-羟色胺转运体的结合具有更高的选择性。将本研究的放射性配体数据与其他WIN 35,065 - 2类似物获得的放射性配体数据进行比较表明，WIN 35,065 - 2类某些类似物的C-2取代基的疏水性可能是其与DA转运体结合的一个重要因素。
