# Recent Updates on the Synthesis of Bioactive Quinoxaline-Containing Sulfonamides
## 1 Introduction  
Heterocyclic scaffolds hold a pivotal place in medicinal chemistry and are one of the largest areas of research in organic chemistry due to their wide spectrum of biological activities. Therefore, continuous efforts have been undertaken to explore their therapeutic potential in the field of design and development of new drugs. Quinoxaline **1** is a privileged, ubiquitous and versatile nitrogen-containing heterocyclic motif, which exhibits a broad spectrum of medicinal, pharmacological and pharmaceutical applications. Quinoxaline, also known as benzopyrazine, was formed by the combination of pyrazine **2** and benzene **3** rings at the carbons 2 and 3 of the pyrazine ring (Figure 1) [1, 2, 3, 4, 5]. Quinoxaline derivatives are of relevant interest in medicinal chemistry because of a wide range of pharmacological and biological activities, such as antitumor, anticancer [6, 7, 8, 9, 10, 11, 12], antidiabetic [13, 14, 15, 16, 17], antimycobacterium tuberculosis [18, 19], antimicrobial [20, 21, 22], antidepressant [23], anthelmmitic [24], analgesic [25, 26, 27, 28, 29, 30, 31], anti-inflammatory [32, 33, 34, 35, 36], antiviral [37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49], anti-malarial [50, 51, 52, 53, 54, 55], antibacterial [56, 57, 58, 59, 60, 61, 62, 63], antioxidant [64, 65, 66], antithrombotic [66, 67] and antiprotozoan [54, 68]. Different quinoxaline-based drugs have been playing a main role in the therapy and treatment of various diseases, such as varenicline **4** (aids in smoking cessation), brimonidine **5** (anti-galucoma activity), quinacillin **6** (antibacterial activity) and XK469 NSC **7** (selective topoisomerase II\(\beta\) poison) (Figure 2) [69; 70; 71]. Sulfonamides were first characterized in 1932 and are organic chemical frameworks in which a sulfonyl group is linked to an amine group (-SO\({}_{2}\)-NR\({}^{1}\)R\({}^{2}\)) [72]. The sulfonamide group is a key moiety that plays a paramount role in both medicinal chemistry and organic chemistry due to their immense biological action. A series of therapeutic agents contain a sulfonamide moiety in their chemical structures [73; 74; 75; 76; 77; 78; 79]. Particular examples are antibiotics which are used on a large scale for many clinical purposes [80]. Heterocyclic sulfonamides exhibit different biological activities, such as antibacterial [81; 82; 83], anti-inflammatory [84], antibacterial [85], antimicrobial [86], antifungal [87], antiprotezoal [88], antiviral [89], anti-malarial [90], antitumor [91; 92; 93], carbonic anhydrase inhibitors [94; 95; 96; 97; 98; 99], antidiabetic [100], anticonvulsant, [101], anti-galucoma [95; 97], anti-obesity [102], diuretic [103; 104; 105], hypoglycemic [95; 97], anti-neuropathic pain [106], matrix metalloproteinase and bacterial protease inhibitors [107; 108]. The sulfonamide moiety is a basic component of drugs such as sulfamethazine 8 (antibacterial), chlorotalidone 9 (diuretic), sulfametopyrazine 10 (chronic bronchitis, urinary tract infections and malaria), chlorpropamide 11 (treats diabetes mellitus type 2), ethoxzolamide 12 (carbonic anhydrase inhibitor) and mafenide 13 (anticriboal agent used to treat severe burns) (Figure 3) [109]. Hybrid structures formulated by the combination of quinoxaline and sulfonamide moieties display novelty and versatility and possess a consistent therapeutic potential against most diseases. The general structure of quinoxaline sulfonamide 14, sulfaquinxaline 15 ( antimicrobial and a coccidiosis for veterinary use) and chloroquinoxaline sulfonamide 16 (topoisomerase-II\(\alpha\) and a topoisomerase-II\(\beta\) poison) are depicted in Figure 4[110]. The significance of quinoxaline sulfonamide derivatives in medicinal chemistry as therapeutic agents is clearly displayed by the patents.