New Pyrazolo[1′,5′:1,6]pyrimido[4,5-d]pyridazin-4 (3H)-ones Fluoroderivatives as Human A1 Adenosine Receptor Ligands

被引：0

作者：

Graziano, Alessia ^{[1
]}

Giovannoni, Maria Paola ^{[1
]}

Cilibrizzi, Agostino ^{[1
]}

Crocetti, Letizia ^{[1
]}

Dal Piaz, Vittorio ^{[1
]}

Vergelli, Claudia ^{[1
]}

Trincavelli, Maria Letizia ^{[2
]}

Martini, Claudia ^{[2
]}

Giacomelli, Chiara ^{[2
]}

机构：

[1] Dipartimento Sci Farmaceut, I-50019 Sesto Fiorentino, Italy

[2] Univ Pisa, Dipartimento Psichiatria Neurobiol Farmacol & Bio, I-56126 Pisa, Italy

来源：

ACTA CHIMICA SLOVENICA | 2012年 / 59卷 / 03期

关键词：

Adenosine receptors; A(1) subtype; Ligands; Pyrazolo[1 ',5 ':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones; BEARING POLAR SUBSTITUENTS; POTENT; PHARMACOLOGY; DESIGN;

D O I：

暂无

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In this paper we report the synthesis and biological evaluation of a new series of pyrazolo[1',5': 1,6] pyrimido[4,5-d]pyridazin-4(3H)-ones as human A(1) adenosine receptor ligands. The tricyclic scaffold was modified at position 6 and 9 by introducing small alkyl chains and substituted phenyls. The most interesting compounds showed Ki for A(1) in the submicromolar range (0.105-0.244 mu M) and the most interesting term (compound 4c) combined an appreciable affinity for A(1) (Ki = 0.132 mu M) with a good selectivity toward A(2A) (43% inhibition at 10 mu M) and A(3) (46% inhibition at 10 mu M).

引用

页码：648 / 655

页数：8

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