Dipartimento di Scienze Farmaceutiche, Università di Trieste, Piazzale Europa 1, I-34127, Trieste, Italy.
Purinergic Signal. 2008 Mar;4(1):39-46. doi: 10.1007/s11302-007-9058-y. Epub 2007 Jul 25.
In the last few years, many efforts have been made to search for potent and selective human A(3) adenosine antagonists. In particular, one of the most promising human A(3) adenosine receptor antagonists is represented by the pyrazolo-triazolo-pyrimidine family. This class of compounds has been strongly investigated from the point of view of structure-activity relationships. In particular, it has been observed that fundamental requisites for having both potency and selectivity at the human A(3) adenosine receptors are the presence of a small substituent at the N(8) position and an unsubstitued phenyl carbamoyl moiety at the N(5) position. In this study, we report the role of the N(5)-bond type on the affinity and selectivity at the four adenosine receptor subtypes. The observed structure-activity relationships of this class of antagonists are also exhaustively rationalized using the recently published ligand-based homology modeling approach.
在过去的几年中,人们进行了许多努力来寻找有效且选择性高的人 A(3) 腺苷拮抗剂。特别是,吡唑并三唑嘧啶家族代表了最有前途的人 A(3) 腺苷受体拮抗剂之一。从结构活性关系的角度来看,人们对这一类化合物进行了深入的研究。特别是,人们观察到,在人 A(3) 腺苷受体上具有效力和选择性的基本要求是在 N(8) 位置上存在小取代基,并且在 N(5) 位置上存在未取代的苯甲酰胺部分。在这项研究中,我们报告了 N(5)-键类型对四种腺苷受体亚型的亲和力和选择性的作用。还使用最近发表的基于配体的同源建模方法来详尽地解释了此类拮抗剂的观察到的构效关系。