Synthesis and biological evaluation of a new set of pyrazolo[1,5-c]quinazolines as glycine/N-methyl-D-aspartic acid receptor antagonists.
In: Chemical & pharmaceutical bulletin, Jg. 57 (2009-08-01), Heft 8, S. 826-9
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Zugriff:
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.
Titel: |
Synthesis and biological evaluation of a new set of pyrazolo[1,5-c]quinazolines as glycine/N-methyl-D-aspartic acid receptor antagonists.
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Autor/in / Beteiligte Person: | Varano, F ; Catarzi, D ; Colotta, V ; Poli, D ; Filacchioni, G ; Galli, A ; Costagli, C |
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Zeitschrift: | Chemical & pharmaceutical bulletin, Jg. 57 (2009-08-01), Heft 8, S. 826-9 |
Veröffentlichung: | Tokyo, Pharmaceutical Society of Japan., 2009 |
Medientyp: | academicJournal |
ISSN: | 0009-2363 (print) |
DOI: | 10.1248/cpb.57.826 |
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