4,5-dihydro-1H-pyrazole derivatives with inhibitory nNOS activity in rat brain: synthesis and structure-activity relationships.
In an attempt to find new compounds with neuroprotective activity, we have designed, synthesized and characterized 19 new nNOS inhibitors with a 4,5-dihydro-1H-pyrazole structure. Compounds 11r [1-cyclopropanecarbonyl-3-(2-amino-5-chlorophenyl)-4,5-dihydro-1H-pyrazole] and 11e [1-cyclopropanecarbonyl-3-(2-amino-5-methoxyphenyl)- 4,5-dihydro-1H-pyrazole] show the highest activities with inhibition percentages of 70% and 62%, respectively. A structure-activity relationship for the nNOS inhibition can be established from the structural comparison of these new pyrazole derivatives and the described synthetic kynurenines 10.
Camacho
M Encarnación
ME
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Spain.
León
Josefa
J
Entrena
Antonio
A
Velasco
Guillermo
G
Carrión
M Dora
MD
Escames
Germaine
G
Vivó
Antonio
A
Acuña-Castroviejo
Darío
D
Gallo
Miguel A
MA
Espinosa
Antonio
A
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D007737:Kynurenine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
C494340:1-cyclopropanecarbonyl-3-(2-amino-5-chlorophenyl)-4,5-dihydro-1H-pyrazole; C494341:1-cyclopropanecarbonyl-3-(2-amino-5-methoxyphenyl)-4,5-dihydro-1H-pyrazole; D000814:Aniline Compounds; D011720:Pyrazoles; D007737:Kynurenine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat