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.