Synthesis and pharmacological evaluation of analogs of indole-based cannabimimetic agents

Aminoalkylindoles (AAIs), although structurally dissimilar from the classical cannabinoids, are known to be capable of binding to cannabinoid receptors and of evoking cannabinomimetic responses. With the aim of investigating the structure-activity relationships (SAR) for the binding of non-classical agonists to CB1 and CB2 cannabinoid receptors, we designed and synthesized a series of indole derivatives. The compounds were tested for their analgesic action by formalin test and compared to WIN 55212-2, an AAI acting to the cannabinoid receptors. In receptor binding assay, compound 5 showed affinity for the CB1 receptor comparable to WIN 55212-2. © 2009 John Wiley & Sons A/S

Design and synthesis of small libraries of peptidomimetics based on a thiazolidine moiety

A short and general synthesis for the preparation of two series of conformationally constrained building block has been elaborated starting from amino acids. The intrinsic tendency of the dipeptide mimetic scaffold to induce β-turn formation was evaluated by computer methods. The results indicate that the diastereomers with the (R) configuration at the C-2 have high propensity to the type II β-turn formation

Synthesis of novel indole-based ring systems by acid-catalysed condensation from α -amino aldehydes and L-Trp-OMe

Acid-catalysed condensation of tryptophan with different α-amino aldehyde derivatives has been explored as a useful route to the synthesis of novel amino acid derived heterocycles and peptidomimetic scaffolds. By this approach, compounds containing a tetrahydro-β-carboline and a novel octahydropyrrolo[3′,2′:3,4]pyrrolo[2,3-b]indole system have been efficiently synthesized. Here we report the characterization of these new compounds and preliminary studies of the reactivity of the tetrahydro-β-carboline system