Synthesis and Docking of Novel 3 ‐Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5‐HT1AR/SERT

A series of novel 3‐indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin‐1A receptor subtype (5‐HT1AR) and the 5‐HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5‐HT1AR (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all the compounds unveiled relevant drug–target interactions, which allowed rationalizing the observed affinities.

A series of novel 3‐indolylpropyl derivatives were synthesized and evaluated for their binding affinities at the serotonin transporter (SERT) and the 5‐HT1A receptor. 1‐Benzyl‐3‐{4‐[3‐(5‐methoxy‐1H‐3‐indolyl)propyl]‐1‐piperazinylmethyl}‐1H‐indole 11b and (1‐benzyl‐5‐fluoro‐1H‐3‐indolylmethyl)‐(4‐{4‐[3‐(5‐methoxy‐1H‐3‐indolyl)propyl]‐1‐piperazinyl}phenyl)amine 14b exhibited the highest affinities at the 5‐HT1A receptor (Ki = 42.7 and 55.8 nM).

Source: Archiv der Pharmazie - November 30, 2016 Category: Drugs & Pharmacology Authors: Hern án Pessoa‐Mahana, Paul Silva‐Matus, C. David Pessoa‐Mahana, Hery Chung, Patricio Iturriaga‐Vásquez, Gabriel Quiroz, Patricia Möller‐Acuña, Gerald Zapata‐Torres, Claudio Saitz‐Barría, Ramiro Araya‐Maturana, Miguel Reyes‐Parada Tags: Full Paper Source Type: research