Grupo de Estudos em Quimica Organica e Biologica (GEQOB), Departamento de Quimica, ICEx, Universidade Federal de Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
Curr Drug Targets. 2013 Mar;14(3):378-97. doi: 10.2174/138945013804999043.
Tacrine was the first drug approved by FDA for the treatment of Alzheimer's disease. However, its use was restricted in function of side effects observed in some patients. Investigations on the structural basis by which tacrine inhibits cholinesterases activity brought new perspectives for the design of more potent analogs with fewer side effects. This review discusses the recent advances on the development of tacrine-structure-based compounds capable to target multiple molecules involved in Alzheimer's disease. Detailed information on strategies of molecular modifications commonly used in medicinal chemistry, such as bioisosterism, hybridization, dimerization and simplification is presented as well.
他克林是 FDA 批准用于治疗老年痴呆症的第一种药物。然而，由于在一些患者中观察到的副作用，其使用受到限制。对他克林抑制胆碱酯酶活性的结构基础的研究为设计具有更少副作用的更有效类似物提供了新的视角。本文综述了基于他克林结构的化合物在治疗阿尔茨海默病的多靶点药物开发方面的最新进展。还介绍了药物化学中常用的分子修饰策略的详细信息，如生物等排、杂化、二聚化和简化等。
