Synthesis and biological investigations of 3β-aminotropane arylamide derivatives with atypical antipsychotic profile

Abstract

This work is a continuation of our previous research, concentrating this time on lead structure modification to increase the 5-HT1A receptor affinity and water solubility of designed compounds. Therefore, the compounds synthesised within the present project included structural analogues of 3β-acylamine derivatives of tropane with the introduction of a methyl substituent in the benzyl ring and a 2-quinoline, 3-quinoline, or 6-quinoline moiety. A series of novel 3β-aminotropane derivatives was evaluated for their affinity for 5-HT1A, 5-HT2A, and D2 receptors, which allowed for the identification of compounds 12e, 12i, and 19a as ligands with highest affinity for the tested receptors; they were then subjected to further evaluation in preliminary in vivo studies. Selected compounds 12i and 19a displayed antipsychotic properties in the d-amphetamine-induced and MK-801-induced hyperlocomotor activity test in mice. Moreover, compound 19a showed significant antidepressant-like activity in the forced swim test in mice.

Recent advances in dopamine D2 receptor ligands in the treatment of neuropsychiatric disorders

“…As a continuation of previous studies, 668,669 various 3β‐aminotropanes were developed with atypical antipsychotic profiles 674 . These modulators were evaluated for their affinity toward D 2 , 5‐HT 1A , and 5‐HT 2A receptors.…”

“…669 As a continuation of previous studies, 668,669 various 3β-aminotropanes were developed with atypical antipsychotic profiles. 674 These modulators were evaluated for their affinity toward D 2 , 5-HT 1A , and 5-HT 2A receptors. The purpose of this study was to continue searching for new compounds with antipsychotic potential in group of derivatives based on β66d 669 (Figure 38).…”