Details

Autor(en) / Beteiligte

• Colotta, Vittoria
• Catarzi, Daniela
• Varano, Flavia
• Cecchi, Lucia
• Filacchioni, Guido
• Martini, Claudia
• Trincavelli, Letizia
• Lucacchini, Antonio

Titel

Synthesis and Structure−Activity Relationships of a New Set of 2-Arylpyrazolo[3,4-c]quinoline Derivatives as Adenosine Receptor Antagonists

Ist Teil von

• Journal of medicinal chemistry, 2000-08, Vol.43 (16), p.3118-3124

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2000

Quelle

MEDLINE

Beschreibungen/Notizen

• In a recent paper (Colotta et al. J. Med. Chem. 2000, 43, 1158−1164) we reported the synthesis and adenosine receptor binding activity of two sets of 2-aryl-1,2,4-triazolo[4,3-a]quinoxalines (A and B) some of which were potent and selective A1 or A3 antagonists. In this paper the synthesis of a set of 2-arylpyrazolo[3,4-c]quinolin-4-ones 1 − 10, 4-amines 11 − 18, and 4-amino-substituted derivatives 19 − 35 are reported. The binding activity at bovine A1 and A2A and human cloned A3 adenosine receptors showed that (i) the substituent on the appended 2-phenyl ring could be used to modulate A1 and A3 affinity, (ii) the 4-amino group was necessary for A1 and A2A binding activity, and (iii) a nuclear or extranuclear CO proton acceptor at position 4 yielded potent and selective A3 antagonists. These results are in agreement with those of the previously reported series A and B suggesting a similar adenosine receptor binding mode. In particular, the A3 nanomolar affinity of 1 − 8, 31 − 33, and 35 confirms the hypothesis of the presence in the N-6 region of the adenosine A3 subtype of a proton donor able to bind to a CO proton acceptor at position 4.