The present work is divided to two parts: 1) Applied Pharmacochemistry and 2) Computational Pharmacochemistry 1) Applied Pharmacochemistry: New heterocyclic chemotypes are synthesized that are derivatives of: i) the octahydroindolquinoline that may be useful for the pharmacotherapy of depression and ii) 2,4- and 2,5- substituted pyrroles that may be useful for the pharmacotherapy of the chronic complications of diabetes mellitus. These structures were designed based on molecular modeling methods. Their biological profile was studied based on biochemical models. For the synthesis of the compounds, known reactions, appropriately modified, were applied as well as novel synthetic procedures were developed. The aim was to find simple and efficient methodologies for the synthesis of the compounds. A total of 4 target compounds were isolated, one of them is an indole derivative and the others are pyrrole derivatives. Furthermore, 36 intermediates were synthesized, from which 25 are new compounds, 7 are pyrrole derivatives and 18 are indole derivatives. a) The synthesis of the tetracyclic compound, which is an indole derivative, involves a successful cyclization at the 4-position of the indole ring. This is carried out using a novel Friedel-Crafts cyclization system. The new indole derivative was tested in vitro for its affinity for serotonin receptors (5-HT1A, 5-HT2A and 5-HT1C) and dopamine receptors (D1 and D2). It was found that the compound acts mainly at 5-HT2C receptors whereas it expresses no binding affinity at dopamine receptors. Also, it was tested in vitro for its ability to inhibit the enzyme aldose reductase and to inhibit in vitro the irreversible modification of proteins. The above three in vitro models are related to depression and the results demonstrate desirable biological properties for the pharmacotherapy of mood disorders. Finally, it was tested ex vivo for its intestinal permeability while its polar molecular surface area was calculated. These two parameters are related to passive permeability through biomembranes. Taken together, the above results indicate that the compound could be given per os and it could penetrate the blood brain barrier. b) The synthesis of the pyrrole derivatives was carried out based on Friedel- Crafts acylations. It was found that, for these reactions, the presence of nitromethane was necessary. Intramolecular aroyl migration was also observed and a possible mechanism is proposed. The new pyrrole derivatives were tested in vitro for their ability to inhibit the enzyme aldose reductase. It was found that two of them are strong inhibitors in nanomolar concentrations. The compound that was found to be the more potent aldose reductase inhibitor was studied for its ability to inhibit in vitro the irreversible modification of proteins. It was found to be as effective as trolox. 2) Computational Pharmacochemistry: A number of physicochemical properties were calculated for several molecules with different structures. For the calculation of a number of physicochemical properties, a Monte-Carlo conformational search was first performed to identify a low energy conformer. The calculated properties and the ability of the compounds to inhibit the enzyme aldose reductase were correlated using regression analyses. It was found that the inhibition is favored from rigid molecules, molecules for which the conformations have a significant difference in their energy. It was also found that the inhibition influenced positively from high values of EHOMO and maximum electrostatic potential. These results could contribute to the development of overall more active compounds.