Benzofuran (oxygen heterocycle) is a common moiety found in many biologically active natural and therapeutic products, and thus represents a very important pharmacophore. It is present in many medicinally important compounds that show biological activity, including anticancer and antiviral properties. Some benzofuran derivatives are also known as 5-lipoxygenase inhibitors, antagonists of the angiotensin II receptor, blood coagulation factor Xa inhibitors, ligands of adenosine A1 receptor and more recently as MAO inhibitors. In general, benzofurans described as MAO inhibitors have a higher selectivity to the MAO-B isoform. In our efforts to contribute to the development of novel compounds that may be useful in the treatment of neurodegenerative disorders such as PD or AD, we are focusing on 2-phenylbenzofuran derivatives. 2-Phenylbenzofurans have been selected by analogy to 3-phenylcoumarins previously described by us as potent and selective MAO-B inhibitors, and preserving the core of trans-stilbene in their structure. Based on these previous experimental results, and with the aim of finding novel and more selective MAO-B inhibitors, in the present work we continue our studies, describing the synthesis of a new series of nitro-substituted 2-phenylbenzofurans derivatives in order to compare experimental results.