Catarzi Daniela, Varano Flavia, Falsini Matteo, Varani Katia, Vincenzi Fabrizio, Pasquini Silvia, Dal Ben Diego, Colotta Vittoria
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, Italy.
Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, Italy.
Bioorg Med Chem Lett. 2018 May 15;28(9):1484-1489. doi: 10.1016/j.bmcl.2018.03.086. Epub 2018 Mar 30.
With the aim of finding new adenosine receptor (AR) ligands, a preliminary investigation focusing on the thieno[2,3-d]pyridazin-5(4H)-one scaffold was undertaken. The synthesized compounds 1-11 were evaluated for their binding at hA, hA and hA ARs and efficacy at hA subtype in order to determine the affinity at the human adenosine receptor subtypes. Small structural changes on this scaffold highly influenced affinity; compound 5 (5-ethyl-7-(thiazol-2-yl)thieno[2,3-d]pyridazin-4(5H)-one) emerged as the best of this series. The simplicity of the synthetic process, the capability of the scaffold to be easily decorated, together with the predicted ADME properties confirm the role of these compounds as promising hits. A molecular docking investigation at the hAAR crystal structure was performed to rationalize the SARs of the herein reported thienopyridazinones.
为了寻找新的腺苷受体（AR）配体，开展了一项针对噻吩并[2,3-d]哒嗪-5(4H)-酮骨架的初步研究。对合成的化合物1-11进行了它们在hA、hA和hA ARs上的结合以及在hA亚型上的活性评估，以确定其对人腺苷受体亚型的亲和力。该骨架上的微小结构变化对亲和力有很大影响；化合物5（5-乙基-7-(噻唑-2-基)噻吩并[2,3-d]哒嗪-4(5H)-酮）成为该系列中表现最佳的化合物。合成过程的简单性、骨架易于修饰的能力以及预测的ADME性质证实了这些化合物作为有前景的先导化合物的作用。对hAAR晶体结构进行了分子对接研究，以阐明本文报道的噻吩并哒嗪酮的构效关系。
