tropoxane tropoxane tropoxane (o-1072) is an aryloxytropane derivative drug developed by organix inc., which acts as a stimulant and potent dopamine and serotonin reuptake inhibitor. it is an analogue of dichloropane where the amine nitrogen has been replaced by an oxygen ether link (at the bridgehead position), demonstrating that the amine nitrogen is not required for dat binding and reuptake inhibition. tropoxaneclinical dataatc codenoneidentifiers iupac name methyl (1r,2s,3s,5s)-3-(3,4-dichlorophenyl)-8-oxabicyclooctane-2-carboxylate pubchem cid9796921chemspider7972687chemical and physical dataformulac15h16cl2o3molar mass315.19 g·mol−13d model (jsmol)interactive image smiles clc1ccc(cc1cl)2c3o(2c(=o)oc)cc3 inchi inchi=1s/c15h16cl2o3/c1-19-15(18)14-10(7-9-3-5-13(14)20-9)8-2-4-11(16)12(17)6-8/h2,4,6,9-10,13-14h,3,5,7h2,1h3/t9-,10+,13+,14-/m0/s1key:dhxanqgcravcsq-pjqznrqzsa-n (verify) thia analog the 8-thiabicyclo(3.2.1)octanes analogs such as o-4210 have been prepared. a representative set of analogs is listed below. mat ic50 (nm) 8-thiabicyclooctanes xcomdatsertcomdatsertcomdatsert h1a910>10um2a140>8um3a117>3um f1b220>30um2b59>11um3b38494 cl1c13>10um2c111um3c9.633 br1d9.1>25um2d6.03423d6.014 i1e6.7>8um2e9.0703e1410 cl21f4.5>3um2f6.9993f5.78.0 bn1g8.0>1um2g8.0363g1613 it had been hypothesized that transporter binding of the tropanes might include ionic bonding of the central tropane nitrogen. but it turned out that at this site neither ionic nor hydrogen bonding is a prerequisite for potent monoamine reuptake inhibition. oxa- and thia-analogs of rti-111 are potent inhibitors, and even an n-replacement by methylene holds the potency within the same magnitude. however, n-quaternisation (n-dimethyl) considerably reduces dat affinity. in this sar, the focus is on seeing the effect of changing 8-nme to s, o, or ch2. both enantiomers, as well as the racemates are presented in several cases for comparison. mat ic50 (nm) cl2 bicyclooctanes enant.xcomdatsertcomdatsertcomdatsert racs1a4.53,6002a6.9993a5.78.0 raco1a106,0002a3.164.53a3.36.5 1rnme1a1.28672a0.4273a1.12.5 racch21a7.15,1602a131663a9.633