Pyrrolopyrazine derivatives: synthetic approaches and biological activities

Nitrogen-containing heterocycles were employed in different applications such as pharmaceuticals, organic materials, natural products, and mainly in bioactive molecules. Pyrrolopyrazine as a biologically active scaffold contains pyrrole and pyrazine rings. Compounds with this scaffold have widely exhibited different biological activities, such as antimicrobial, anti-inflammatory, antiviral, antifungal, antioxidant, antitumor, and kinase inhibitory. In addition, many pyrrolopyrazine derivatives have been isolated from plants, microbes, soil, marine life, and other sources. This review explained various synthetic routes for pyrrolopyrazine derivatives, including cyclization, ring annulation, cycloaddition, direct C-H arylation, and other methods. Besides, pyrrolopyrazines are classified into three chemical categories with two or three nitrogen atoms, indicating various biological activities. According to the findings, pyrrolo [1,2- a ] pyrazine derivatives exhibited more antibacterial, antifungal, and antiviral activities, while 5H-pyrrolo [2,3- b ] pyrazine derivatives showed more activity on kinase inhibition. However, studies show that the action mechanisms of pyrrolopyrazine derivatives are not clearly recognized. Moreover, despite the scaffold’s importance, there are only a few Structure-Activity Relationship (SAR) research on it. Therefore, the synthetic methods and biological activities of pyrrolopyrazine derivatives discussed in this paper will certainly help medicinal chemistry researchers design and synthesize new leads to treat various diseases. Highlights Pyrrolopyrazine scaffold is a nitrogen-containing heterocyclic compound that includes a pyrrole ring and a pyrazine ring. A wide range of biological activities related to pyrrolopyrazine scaffold is discussed. This review provides the recent efficient synthetic methods for the pyrrolopyrazines. The pyrrolopyrazine structure is an attractive scaffold for drug discovery research.