Previous studies have shown that 8-chloro-5,6-dihydro-5-oxo-pyrazolo[1,5-c]quinazoline-2-carboxylates (PQZ series) represent a family of glycine/N-methyl-D-aspartic acid (NMDA) and/or (R,S)-2-amino-3-(3-hydroxy- 5-methylisoxazol-4-yl)propionic acid (AMPA) and/or kainic acid (KA) receptor antagonists. Moreover, some groups have been identified that introduced in suitable positions of the PQZ 2-carboxylate framework shift affinity and selectivity toward glycine/NMDA receptor. These substituents are a carboxylate function at position-1 and/or a chlorine atom at position-9. In this paper we report a study on some new 5,6-dihydro-5-oxo-pyrazolo[ 1,5-c]quinazoline-1-carboxylates bearing at position-2 a lipophilic amide group or lacking substituent at this same position. All the newly synthesised compounds were evaluated for their binding at glycine/NMDA, AMPA and KA receptors. These studies led to the identification of some new PQZ derivatives endowed with good glycine/NMDA receptor affinity and selectivity and to better definition of the structure–activity relationship (SAR) of this class of compounds.

Synthesis and biological evaluation of a new set of pyrazolo[1,5-c]quinazolines as glycine/N-methyl-D-aspartic acid receptor antagonists / F. Varano; D. Catarzi; V. Colotta; D. Poli; G. Filacchioni; A. Galli; C. Costagli. - In: CHEMICAL & PHARMACEUTICAL BULLETIN. - ISSN 0009-2363. - STAMPA. - 57:(2009), pp. 826-829.

Synthesis and biological evaluation of a new set of pyrazolo[1,5-c]quinazolines as glycine/N-methyl-D-aspartic acid receptor antagonists

VARANO, FLAVIA;CATARZI, DANIELA;COLOTTA, VITTORIA;POLI, DANIELA;FILACCHIONI, GUIDO;GALLI, ALESSANDRO;
2009

Abstract

Previous studies have shown that 8-chloro-5,6-dihydro-5-oxo-pyrazolo[1,5-c]quinazoline-2-carboxylates (PQZ series) represent a family of glycine/N-methyl-D-aspartic acid (NMDA) and/or (R,S)-2-amino-3-(3-hydroxy- 5-methylisoxazol-4-yl)propionic acid (AMPA) and/or kainic acid (KA) receptor antagonists. Moreover, some groups have been identified that introduced in suitable positions of the PQZ 2-carboxylate framework shift affinity and selectivity toward glycine/NMDA receptor. These substituents are a carboxylate function at position-1 and/or a chlorine atom at position-9. In this paper we report a study on some new 5,6-dihydro-5-oxo-pyrazolo[ 1,5-c]quinazoline-1-carboxylates bearing at position-2 a lipophilic amide group or lacking substituent at this same position. All the newly synthesised compounds were evaluated for their binding at glycine/NMDA, AMPA and KA receptors. These studies led to the identification of some new PQZ derivatives endowed with good glycine/NMDA receptor affinity and selectivity and to better definition of the structure–activity relationship (SAR) of this class of compounds.
57
826
829
F. Varano; D. Catarzi; V. Colotta; D. Poli; G. Filacchioni; A. Galli; C. Costagli
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/372890
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