Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and iNOS) potential inhibitors (III)

Abstract

We have previously described a series of 4,5-dihydro-1 H-pyrazole as moderately potent nNOS inhibitors. As a follow up of these studies, we report here the preparation and the preliminary evaluation of a series of 1-alkyl-3-benzoyl-4,5-dihydro-1 H-pyrazole and 1-alkyl-3-benzoyl-1 H-pyrazole as potential inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS). None of the reported compounds exhibited significant iNOS or nNOS inhibition, although the 1-benzyl-3-(2-amino-5-chlorobenzoyl)-1 H-pyrazole-5-carboxylic acid ethyl ester derivative ( 10l), which shows an inhibition of 50% versus iNOS at a 1 mM final concentration and no activity against nNOS, is potentially amenable of further optimization. The reasons for the inactivity of the reported series are discussed on the basis of docking studies.