Adenosine is an endogenous purine-based nucleoside expressed nearly in all body tissues. It regulates various body functions by activating four G-protein coupled receptors, A₁, A_2A, A_2B, and A₃. These receptors are widely acknowledged as drug targets for treating different neurological, metabolic, and inflammatory diseases. Although numerous adenosine receptor inhibitors have been developed worldwide, achieving target selectivity is still a big hurdle in drug development. However, the identification of specific radioligands-based affinity assay, fluorescent ligands, and MS-based ligand assay have contributed to the development of selective and potent adenosine ligands. In recent years various small heterocyclic-based molecules have shown some promising results. Istradefylline has been approved for treating Parkinson's in Japan, while preladenant, tozadenant, CVT-6883, MRS-1523, and many more are under different phases of clinical development. The present review is focused on the quest to develop potent and selective adenosine inhibitors from 2013 to early 2021 by various research groups. The review also highlights their biological activity, selectivity, structure-activity relationship, molecular docking, and mechanistic studies. A special emphsesis on drug designing strategies has been also given the manuscript. The comprehensive compilation of research work carried out in the field will provide inevitable scope for designing and developing novel adenosine inhibitors with improved selectivity and efficacy.

腺苷是一种几乎在所有身体组织中表达的内源性嘌呤核苷。它通过激活四种 G 蛋白偶联受体 A ₁、A _2A、A _2B和 A _{3来调节各种身体功能}. 这些受体被广泛认为是治疗不同神经、代谢和炎症疾病的药物靶点。尽管世界范围内已经开发了许多腺苷受体抑制剂，但实现靶点选择性仍然是药物开发的一大障碍。然而，基于特定放射性配体的亲和力测定、荧光配体和基于 MS 的配体测定的鉴定有助于开发选择性和有效的腺苷配体。近年来，各种基于杂环的小分子已显示出一些有希望的结果。Istradefylline 已在日本被批准用于治疗帕金森氏症，而 preladenant、tozadenant、CVT-6883、MRS-1523 等则处于不同的临床开发阶段。本综述的重点是各个研究小组在 2013 年至 2021 年初寻求开发有效和选择性的腺苷抑制剂。该综述还强调了它们的生物活性、选择性、构效关系、分子对接和机理研究。手稿还特别强调了药物设计策略。该领域开展的研究工作的全面汇编将为设计和开发具有更高选择性和功效的新型腺苷抑制剂提供不可避免的范围。