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Synthesis and Biological Evaluation of New Quinazoline and Cinnoline Derivatives as Potential Atypical Antipsychotics
Author(s) -
Alvarado Mario,
Barceló María,
Carro Laura,
Masaguer Christian F.,
Raviña Enrique
Publication year - 2006
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200690001
Subject(s) - chemistry , affinities , quinazoline , cinnoline , dopamine receptor d2 , 5 ht receptor , stereochemistry , serotonin , receptor , selectivity , derivative (finance) , dopamine , combinatorial chemistry , medicinal chemistry , biochemistry , neuroscience , psychology , financial economics , economics , catalysis
Four new diaza analogues ( 14, 15, 23 , and 24 ) of the conformationally constrained aminobutyrophenone derivatives QF0104B ( 5 ) and QF0108B ( 6 ) were synthesized ( Schemes 2 and 3 ), and evaluated for their binding affinities ( Table ) towards the serotonin 5‐HT 2A and 5‐HT 2C , and the dopamine D 2 receptors. Among the new compounds, the quinazoline derivative 15 (=7‐{[4‐(4‐fluorobenzoyl)piperidin‐1‐yl]methyl}‐5,6,7,8‐tetrahydroquinazolin‐5‐one) exhibited the highest affinities towards the serotonin 5‐HT 2A and dopamine D 2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (=7‐{[4‐(4‐fluorobenzoyl)piperidin‐1‐yl]methyl}‐5,6,7,8‐tetrahydro‐3‐methylcinnolin‐5‐one) displayed high selectivity in its binding profile towards the 5‐HT 2C compared to both the 5‐HT 2A and D 2 receptors.