## 1 Introduction  
Heterocyclic scaffolds are interesting chemical structures that are vital in the discovery of novel drugs for the diagnosis and treatment of diseases. Generally, medicinal chemists tether bioactive heterocyclic motifs in order to produce better drugs. Generally, medicinal chemists explore the strategy of combining the entire molecule or a part of the structure such as two or more heterocyclic rings, which can lead to the generation of new types of structures that have potential bioactivities, and this approach is called molecular hybridization (MH). The design, synthesis, and screening of different heterocyclic hybrids are interesting due to their excellent pharmacological properties and ease of preparation. Many heterocyclic rings are privileged structures due to their significant biological profiles. Hybridization can provide these qualities that can further make the drugs with heterocyclic moieties to have better profiles in terms of their pharmacokinetics, pharmacodynamics, and toxicities [1]. The MH approach not only enhances the pharmacological activity of newly prepared compounds but also modulates the pharmacokinetic properties associated with each heterocyclic scaffold [2]. Additionally, heterocyclic hybrids have good interactions with the molecular drug target and they may have a dual or entirely new mode of action [3]. Nine of the 12 drugs approved in 2021 by the US FDA contain one or more privileged heterocyclic rings as their core elements that are crucial for their activity [4]. This state indicates the implication of utilizing heterocyclic scaffolds in drug discovery programs through the MH strategy. Pyrazine and pyrimidine are important six-membered nitrogenous rings belonging to a class of heterocyclic compounds known as diazines that are commonly distributed in many pharmacologically useful compounds. These rings are present as the fundamental pharmacoophoric group in a variety of drug molecules that are used to treat different diseases. The pyrazine scaffold is present in antitubercular drugs, i.e., pyrazinamide and morinamide; bortezomib, an anti-cancer agent used in multiple myeloma; potassium channel blocker antidiabetic-glipizide; antihyperlipidemic triglyceride lipase inhibitor acipimox; and the potassium sparing diuretics, i.e., amiloride and benzamil [5]. On the other hand, pyrimidine is one of the routinely seen scaffold in drug molecules. This ring is particularly found in drugs used as chemotherapeutic agents because of its ability to interfere with the central metabolic pathways including folate and nucleic acid synthesis. Examples of drugs with a pyrimidine nucleus are antibacterial and antimalarial agents targeting the folate pathway: trimethoprim, iclaprim, sulfadimethoxine, pyrimethamine, and sulfadoxine; antimetabolite and ergosterol biosynthesis inhibitor antifungal drugs: flucytosine and voriconazole; antimetabolite anti-cancer agents: 5-fluorouracil and capecitabine; tyrosine kinase inhibitors: imatinib, dasatinib, and nilotinib; antivirals: ara-c, doxorubicin, zidovudine, stavudine, lamivudine, and emtricitabine; and the antitubercular drug capreomycin (Figure 1). Many substituted pyrazine derivatives were reported with potential antibacterial [6; 7; 8; 9; 10; 11], antifungal [12; 13; 14; 15], anticancer [16; 17; 18; 19; 20; 21], antioxidant [22; 23; 24; 25], and antitubercular [9; 26; 27; 28] activities. Similarly, pyrimidine-based compounds also showed excellent antimicrobial (antibacterial and antifungal) [29; 30; 31; 32; 33], antimycobacterial [34; 35; 36; 37; 38], antioxidant [39; 40; 41; 42], cytotoxic and anticancer [43; 44; 45; 46; 47; 48; 49; 50; 51; 52], and antiviral [51; 52; 53] properties. Figure 1: Chemical structures of selected drugs comprising pyrazine and pyrimidine scaffolds. In our previous study, we reported the antimicrobial and antiproliferative activities of chloropyrazine-linked 1,5-benzothazepine hybrids [54].