DOB & DOI
These molecules are, on the left, DOB, and on the right, DOI. These are space-filling representations of the minimum energy conformations of the free bases in a vacuum. The more active R-(-) optical isomers are shown for both of them. The red atoms are in the 2,5-dimethoxy groups, and the blue atom is the amino group in the side chain. Chemically, they're really pretty similar. The only obvious difference is the brown bromine atom on DOB, and the purple iodine atom on DOI. They are both among the most potent substituted amphetamine type hallucinogens known. It has been known for many years that the most active compounds possessed 4-substitutents that were hydrophobic (nonpolar) and resistant to metabolism. Halogens such as bromine and iodine fit this requirement well. Although it is not known for certain why these groups give such high activity, one possibility is that the 4-substituent fits into a hydrophobic region in the serotonin 5-HT2A receptor. Both of these compounds have a quite long duration of action when given to man, probably because they are so resistant to metabolism. The alpha-methyl of the side chain hinders deamination, which is a minor metabolic pathway in any case, and the bromine or iodine atom blocks aromatic hydroxylation at the 4-position, which would otherwise be expected to be an important metabolic route..
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