Synthesis, 5-hydroxytryptamine1A receptor affinity and docking studies of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives.
A series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a-h) was synthesized and evaluated for binding affinity at the human 5-hydroxytryptamine(1A) receptor (5-HT(1A)R) compounds (12b) and (12h) showed the highest 5-HT(1A) receptor affinity (IC(50)=15 nM). Molecular docking studies with all the compounds in a homology model of 5-HT(1A) showed that the main interaction anchoring the ligand in the receptor was a charge-reinforced bond between the protonated nitrogen atom (N-4) of the piperazine ring and Aspartate(3.32).
Department of Organic Chemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Casilla 233, Santiago 1, Chile. hpessoa@ciq.uchile.cl
Hernán
H
Pessoa-Mahana
Catalina Ugarte
CU
Núñez
Ramiro
R
Araya-Maturana
Claudio Saitz
CS
Barría
Gerald
G
Zapata-Torres
Carlos David
CD
Pessoa-Mahana
Patricio
P
Iturriaga-Vasquez
Jaime
J
Mella-Raipán
Miguel
M
Reyes-Parada
Cristian
C
Celis-Barros
D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D007211:Indoles; D010879:Piperazines; D044282:Receptor, Serotonin, 5-HT1A; D000077489:Piperazine; D001224:Aspartic Acid