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Document Report Card

Doc ID CHEMBL1148732
Journal J Med Chem (2007) 50:4061-4074
Title New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies.
Authors Colotta V, Catarzi D, Varano F, Capelli F, Lenzi O, Filacchioni G, Martini C, Trincavelli L, Ciampi O, Pugliese AM, Pedata F, Schiesaro A, Morizzo E, Moro S.
Abstract This paper reports the study of some 2-arylpyrazolo[3,4-c]quinolin-4-ones, 4-amines, and 4-amino-substituted derivatives designed as human A3 adenosine receptor (AR) antagonists. Most of the herein reported compounds showed a nanomolar affinity toward the hA3 receptor subtype and different degrees of selectivity that resulted to be strictly dependent on the presence and nature of the substituent on the 4-amino group. Bulky and lipophilic acyl groups, as well as the benzylcarbamoyl residue, afforded highly potent and selective hA3 receptor antagonists. The selected 4-diphenylacetylamino-2-phenylpyrazoloquinoline (25) and 4-dibenzoylamino-2-(4-methoxyphenyl)pyrazoloquinoline (36), tested in an in vitro rat model of cerebral ischemia, prevented the irreversible failure of synaptic activity induced by oxygen and glucose deprivation in the hippocampus. The observed structure-affinity relationships of this class of antagonists were also exhaustively rationalized using the recently published ligand-based homology modeling (LBHM) approach.
CiteXplore 17665891
DOI 10.1021/jm070123v

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