Synthesis, biological evaluation, and docking studies of N-substituted acetamidines as selective inhibitors of inducible nitric oxide synthase.
New acetamidines structurally related to N-(3-(aminomethyl)benzyl)acetamidine (1, W1400) were designed as inhibitors of inducible nitric oxide synthase (iNOS). Six compounds were found to be selective for iNOS over endothelial nitric oxide synthase (eNOS), and among them, the most active and selective compound was the N-benzylacetamidine 2. A docking study was also performed to shed light on the effects of the structural modifications on the interaction of the designed inhibitors with the NOS.
Maccallini
Cristina
C
Dipartimento di Scienze del Farmaco, Universita G. d'Annunzio, Chieti, Italy.
Patruno
Antonia
A
Besker
Neva
N
Alì
Jamila Isabella
JI
Ammazzalorso
Alessandra
A
De Filippis
Barbara
B
Franceschelli
Sara
S
Giampietro
Letizia
L
Pesce
Mirko
M
Reale
Marcella
M
Tricca
Maria L
ML
Re
Nazzareno
N
Felaco
Mario
M
Amoroso
Rosa
R
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D008958:Models, Molecular; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D013329:Structure-Activity Relationship
C550369:1-(benzylamino)ethaniminium; D000578:Amidines; D001596:Benzylamines; D052247:Nitric Oxide Synthase Type II