Mazindol - Analogs

Analogs

From considering the attached QSAR table we can make the apparent observations:

  1. Desoxylation of the tertiary alcohol in mazindol improves DAT and SERT binding. The compound now behaves as a functional SNDRI instead of predominantly a noradrenaline reuptake inhibitor.
  2. Removal of the p-chloro atom in mazindol means that the compound now only behaves as a noradrenaline reuptake inhibitor.
  3. Changing the size of the imidazoline type ring system in mazindol to the corresponding six-membered homolog increases potency of the resultant compound at the DAT by approximately ten-fold.
n R R' R" hSERT hNET hDAT
1 Cl H OH 94 4.9 43
1 Cl H H 15 6.9 6.0
1 H H OH 2140 2.8 730
1 -C4H4- OH 1.8 4.5 66
2 Cl H OH 53 4.9 3.7
2 OH H OH 60 1.9 59.0
2 OMe H OH 94 4.1 30.4
2 -OCH2O- OH 83 0.62 2.21

To make the six membered (so-called homomazindol) analog, one can simply substitute 1,2-diaminoethane with 1,3-diaminopropane. Importantly, another procedure was also published.

Given the data in the above table, one might also be interested in making the desoxy-mazindol analog. The synthesis for this is facile. Although "mazindane" is relatively stable in air, it is readily oxidized to mazindol upon contact with monoamine oxidaze enzymes present at the DAT.

See also: SNDRI for context.

Read more about this topic:  Mazindol

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