Introduction to Chemistry and Applications of Benzimidazoles

**3**

derivatives [1, 31–33].

**Chapter 1**

Introductory Chapter: Short

Applications of Benzimidazole

Benzimidazole is well known as an important pharmacophore among heterocyclic compounds due to the remarkable medicinal and pharmacological properties of its derivatives [1–3]. Among these currently marketed benzimidazole drugs to treat several diseases, we can mention bendamustine, selumetinib, galeterone, and pracinostat as antitumor agents; pantoprazole, lansoprazole, esomeprazole, and ilaprazole as proton pump inhibitors; bezitramide as an analgesic; mebendazole, albendazole, thiabendazole, and flubendazole as antihelminthics; ridinilazole as antibacterial; astemizole and bilastine as antihistamines; enviradine, samatasvir, and maribavir as antivirals; and candesartan and mibefradil as antihypertensive [1, 4–7]. Recent research recommends benzimidazole derivatives as potential EGFR and erbB2 inhibitors [8, 9], DNA/RNA binding ligands [10, 11], antitumor agents [12–14], anti-Alzheimer agents [15, 16], antidiabetic agents [17, 18], antiparasitic agents [10, 19], antimicrobial agents [20, 21], antiquorum-sensing agents [12], and antimalarial agents [19]. Intensive studies have demonstrated the use of the benzimidazole scaffold as key pharmacophore in clinically approved analgesic and anti-inflammatory agents [22]. Chiral benzimidazole derivatives were found to be NaV1.8 (voltage-gated sodium channels) blockers, which play a key role in the transmission of pain signals, with excellent preclinical in vitro ADME and safety profile [23]. Other benzimidazole derivatives have been shown to be anti-HIV-1 agents through the protection of APOBEC3G protein [24]. Benzimidazoles grafted with aromatic nuclei have been noted as antioxidant agents [25]. A correlation of the grafted organic functions on the benzimidazole scaffold has been found with their therapeutic potential [26]. Thus, carboxylic acids, carbamates, and amidines have been shown to be effective anticancer drugs [26–28], benzimidazole esters were reported as antifungal agents [29], and 2-aminobenzimid-

azole derivatives possesses very good antimicrobial activity [30].

Structure-activity relationship (SAR) studies have shown that 1,2,5,6-sub-

stituted benzimidazoles with various substituents are analgesic and antiinflammatory agents [22]. Also, SAR studies were accomplished for antiviral, anticancer, antihelminthic, antimicrobial, antimycobacterial, antidiabetic, antiprotozoal, antipsychotic, antidepressant, and antioxidant benzimidazole

Insight in Synthesis and

and Its Derivatives

*Maria Marinescu*

**1. Introduction**

#### **Chapter 1**
