title: New 2-arylpyrazolo[4,3-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists.
abstract: In this paper we report the synthesis and biological evaluation of a new class of 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-ones as A(3) adenosine receptor antagonists. We designed a new route based on the Kira-Vilsmeier reaction for the synthesis of this class of compounds. Some of the synthesized compounds showed A(3) adenosine receptor affinity in the nanomolar range and good selectivity as evaluated in radioligand binding assays at human (h) A(1), A(2A), A(2B), and A(3) adenosine receptor subtypes. We introduced several substituents on the 2-phenyl ring. In particular substitution at the 4-position by methyl, methoxy, and chlorine gave optimal activity and selectivity 6c (K(i)hA(1), A(2A)>1000 nM, EC(50)hA(2B)>1000 nM, K(i)hA(3) = 9 nM), 6d (K(i)hA(1), A(2A)>1000 nM, EC(50)hA(2B)>1000 nM, K(i)hA(3) = 16 nM), 6b (K(i)hA(1), A(2A) >1000 nM, EC(50)hA(2B)>1000 nM, K(i)hA(3) = 19 nM). In conclusion, the 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-one derivatives described herein represent a new family of in vitro selective antagonists for the adenosine A(3) receptor.
authors: Dipartimento di Scienze Farmaceutiche, Dipartimento di Medicina Clinica e Sperimentale-Sezione di Farmacologia, Università di Ferrara, 44100 Ferrara, Italy. pgb@dns.unife.it
authors: Pier Giovanni
authors: PG
authors: Baraldi
authors: Mojgan Aghazadeh
authors: MA
authors: Tabrizi
authors: Delia
authors: D
authors: Preti
authors: Andrea
authors: A
authors: Bovero
authors: Francesca
authors: F
authors: Fruttarolo
authors: Romeo
authors: R
authors: Romagnoli
authors: Naser Abdel
authors: NA
authors: Zaid
authors: Allan R
authors: AR
authors: Moorman
authors: Katia
authors: K
authors: Varani
authors: Pier Andrea
authors: PA
authors: Borea
mesh_terms: D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D043684:Receptor, Adenosine A3 / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D011720:Pyrazoles; D011804:Quinolines; D043684:Receptor, Adenosine A3; D000242:Cyclic AMP