Tosh Dilip K, Jacobson Kenneth A
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Medchemcomm. 2013 Dec 17;2013(4):619-630. doi: 10.1039/C2MD20348K.
Adenosine receptors (ARs) and P2Y receptors for purine and pyrimidine nucleotides have widespread distribution and regulate countless physiological processes. Various synthetic ligands are in clinical trials for treatment of inflammatory diseases, pain, cancer, thrombosis, ischemia, and other conditions. The methanocarba (bicyclo[3.1.0]hexane) ring system as a rigid substitution for ribose, which maintains either a North (N) or South (S) conformation, tends to preserve or enhance the potency and/or selectivity for certain receptor subtypes. This review summarizes recent developments in the synthetic approaches to these biologically important nucleoside and nucleotide analogues.
嘌呤和嘧啶核苷酸的腺苷受体(ARs)及P2Y受体分布广泛,调节着无数的生理过程。多种合成配体正处于治疗炎症性疾病、疼痛、癌症、血栓形成、局部缺血及其他病症的临床试验阶段。作为核糖的刚性取代基,甲碳环(双环[3.1.0]己烷)环系保持着北(N)或南(S)构象,往往能保留或增强对某些受体亚型的效力和/或选择性。本综述总结了这些具有重要生物学意义的核苷和核苷酸类似物合成方法的最新进展。