The absence of disease modifying drugs in Parkinson's disease therapy urges for new chemical entities acting on relevant PD-associated biological targets. As a result, developing selective and reversible inhibitors targeting MAO-B is still a desirable line of therapeutic research. Within this framework, a small library of chromone derivatives was synthesized and screened towards human monoamine oxidases. Structural modifications on the chromone 3-phenylcarboxamide resulted in potent MAO-B inhibitors with an improved drug-like profile, and for the first time we obtained potent and selective chromone 2-phenylcarboxamides acting in the low nanomolar range. Compounds 5-hydroxy-4-oxo-N-phenyl-4H-chromene-3-carboxamide (38) (IC₅₀ = 13.0 nM) and N-(4-chlorophenyl)-5-hydroxy-4-oxo-4H-chromene-3-carboxamide (41) (IC₅₀ = 8.3 nM) stood out as reversible, potent, selective and non-cytotoxic MAO-B inhibitors bearing a favourable drug-like profile. Both compounds displayed cytoprotective effects towards iron(III) oxidative stressor.

帕金森病治疗中缺乏改善疾病的药物促使新的化学实体作用于相关的 PD 相关生物靶点。因此，开发靶向 MAO-B 的选择性和可逆抑制剂仍然是治疗研究的理想方向。在这个框架内，合成了一个小的色酮衍生物库，并针对人类单胺氧化酶进行了筛选。色酮 3-苯基甲酰胺的结构修饰产生了有效的 MAO-B 抑制剂，具有改善的药物样特性，并且我们首次获得了在低纳摩尔范围内起作用的强效和选择性色酮 2-苯基甲酰胺。化合物 5-hydroxy-4-oxo- N -phenyl-4H-chromene-3-carboxamide ( 38 ) (IC ₅₀  = 13.0 nM) 和N-(4-chlorophenyl)-5-hydroxy-4-oxo-4H-chromene-3-carboxamide ( 41 ) (IC ₅₀  = 8.3 nM) 作为可逆、有效、选择性和非细胞毒性 MAO-B 抑制剂脱颖而出有利的药物样配置文件。两种化合物都显示出对铁 (III) 氧化应激物的细胞保护作用。