Analogues
A number of bupropion analogues were recently reported by F. Ivy Carroll, et al. The aims were two-fold: one smoking cessation, and two, cocaine addiction agents.
In their efforts to find smoking cessation agents, F. Ivy Carroll, et al. also recently (2011) disclosed a number of 2-(substituted phenyl)-3,5,5-trimethylmorpholine analogues.
F. Ivy Carroll, et al. have also produced hydroxy-bupropion analogues, with smoking cessation as the stated application.
Although structurally unrelated to bupropion, F. Ivy Carroll, et al. recently (2011) disclosed a number of 3-phenyltropanes that had some nAChR activity.
Through reading the above citations it would be possible to draw up possible SARs. To give an example, extending the α-methyl chain in bupropion to C3H7 (presumed n-propyl), improved the DA IC50 from 658nM to 56nM. Extending the α-methyl to an α-ethyl also improved DA IC50 to 209nM. According to work done on sibutramine though, the absolute optimum chain length in these compounds is an iso-butyl radical. This has been confirmed by P. Meltzer et al. in his seminal paper on naphyrone analogs. Mark Froimowitz, et al. also explored the effect of replacing the carbomethoxy group in Ritalin with different alkyl groups. In fact, the isobutyl analog of bupropion was also studied by RTI, but DA IC50 was only 140nM.
It can also be readily seen that omission of the hydroxy group in Radafaxine makes DA and NE IC50 shift from 630 and 180nM, respectively, to 220 and 130nM, and 5-HT was 387nM.
Other analogs of desoxy-Radafaxine were also prepared. For example, replacing the m-chloro group with m-fluoro gave an analog that had DA and NE and 5HT IC50 values of 61, 32, and 4600nM, respectively.
A somewhat interesting observation is that in the case of methcathinone, the m-chloro group is not needed as the compound is fully active already. However in the case of bupropion where we have a tert-butyl-N group, omission of the m-chloro halogen gave a compound that had diminished activity as a MAT inhibitor. Moving the m-chloro to the para position also led to a deterioration in the compounds resultant potency.
Read more about this topic: Bupropion
Famous quotes containing the word analogues:
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