Preface

Finding new strategies for synthesizing benzimidazole derivatives and functionalizing the benzimidazole core has proved to be important due to the compound's various applications in medicine, chemistry, and other areas. The development of new domains, such as the chemistry of optically active benzimidazole compounds, is imperative because of the compounds' particular pharmacological properties and their use as catalysts or as ligands.

The multitude of benzimidazole derivatives marketed as drugs has led to intensive research in the field for the discovery of new biologically active structures. The general applications of benzimidazole derivatives in materials chemistry, electronics, technology, dyes, pigments, and agriculture open up new research horizons. This book guides the rational design of benzimidazole derivatives synthesis with certain applications. It is organized as follows:

#### Section I: **Introduction to Chemistry and Applications of Benzimidazoles**

Chapter 1 "**Introductory Chapter: Short Insight in Synthesis and Applications of Benzimidazole and Its Derivatives**" summarizes the general and special methods of synthesis of benzimidazole derivatives as well as a scheme of applications of these compounds in the areas of medicine, pharmacology, and chemistry, among others.

#### Section II: **Chemistry of Benzimidazoles**

Chapter 2 "**Catalytic Intermolecular Functionalization of Benzimidazoles**" presents an updated review on functionalizations of nitrogen and at position C–2 in the benzimidazole scaffold. Functionalization of positions C–4 through C–7 is more challenging as these are less activated. A key success factor for reactions is the various catalytic systems.

Chapter 3 "**X-Ray Crystal Structure Analysis of Selected Benzimidazole Derivatives**" describes the X-ray crystal structure analysis of six selected benzimidazole derivatives. The detailed structural analyses indicate that the planes of benzimidazole units are associated in different modes through hydrogen bonds.

Chapter 4 "**Synthesis and Pharmacological Profile of Benzimidazoles**" summarizes the synthetic methods of benzimidazole derivatives and discusses therapeutic use of benzimidazole in conditions like diabetes, cancer, parasitic diseases, viruses, and allergies, as well as for pain management.

#### Section III: **The Therapeutic Potential of Benzimidazoles**

**II**

**Chapter 7 105**

**Chapter 8 139**

Benzimidazole Derivatives in Chemistry of Materials **157**

**Chapter 9 159**

**Chapter 10 181**

**Chapter 11 203**

Supramolecular Assembly of Benzimidazole Derivatives and Applications

)-ATPase Inhibitors

Benzimidazoles: From Antiproliferative to Multitargeted Anticancer Agents

*by Renukadevi Patil, Olivia Powrozek, Binod Kumar, William Seibel, Kenneth Beaman, Gulam Waris, Neelam Sharma-Walia and Shivaputra Patil*

Optical Sensing (Nano)Materials Based on Benzimidazole Derivatives

*by Ema Horak, Robert Vianello and Ivana Murković Steinberg*

Benzimidazole as Solid Electrolyte Material for Fuel Cells

*by Daniel Herranz and Pilar Ocón*

*by Yousef Najajreh*

**Section 4**

*by Ana Beloqui*

Bisbenzimidazoles: Anticancer Vacuolar (H<sup>+</sup>

Chapter 5 "**Antidiabetogenic Features of Benzimidazoles**" examines the effect of a new cyclic aminobenzimidazole derivative, diabenol, which contains a guanidine group and combines pharmacological effects of biguanides and sulfonylurea derivative of gliclazide. Preclinical and clinical studies are also discussed.

Chapter 6 "**Development of Benzimidazole Compounds for Cancer Therapy**" discusses the synthesis and clinical pharmacology of three anticancer compounds: bendamustine, selumetinib, and galeterone. Based on impressive preclinical data, the University of Maryland, Baltimore, was granted an exclusive license for the development of galeterone for the treatment of patients with castration-resistant prostate cancer.

Chapter 7 "**Benzimidazoles: From Antiproliferative to Multi-targeted Anticancer Agents**" focuses on multi-targeted benzimidazole derivatives reported during the last decade, especially dovitinib and AT9283, reported to exhibit potent in vitro and in vivo activities against a group of kinases and non-kinases. Dovitinib, an anti-neoplastic benzimidazolylquinolinone, inhibits multiple growth factor receptor tyrosine kinases important for tumor angiogenesis and tumor growth and is effective against sixteen colorectal cancer cell lines.

Chapter 8 "**Bisbenzimidazoles: Anticancer Vacuolar (H+)-ATPase Inhibitors**" presents the research on several bisbenzimidazoles as proton pump inhibitors with good antiproliferative activity and very good cytotoxicity over most cancer cell lines.

#### Section IV: **Benzimidazole Derivatives in Chemistry of Materials**

Chapter 9 "**Optical Sensing (Nano)Materials Based on Benzimidazole Derivatives**" reviews benzimidazole derivatives as important materials for multifunctional building blocks in optical chemical sensors, materials for optical sensing, fluorescent sensors, metal organic frameworks, and copolymers.

Chapter 10 "**Benzimidazole as Solid Electrolyte Material for Fuel Cells**" discusses the application of polybenzimidazoles as economical materials for fuel cells with excellent thermal and mechanical properties as well as chemical resistance in acidic and alkaline media.

Chapter 11 "**Supramolecular Assembly of Benzimidazole Derivatives and Applications**" focuses on the chemical and physical properties of benzimidazole and its derivatives used for the synthesis of supramolecular materials, including metalorganic frameworks, metal-coordination polymers, and smart nanocontainers.

I am immensely grateful to IntechOpen and Author Service Manager Ms. Ivana Barac, who offered me the opportunity to be the editor of this book.

I would also like to thank the authors for their valuable contributions.

I hope this book will serve as a guide for students and researchers interested in making advancements in benzimidazole chemistry and applications of these compounds in medicinal chemistry and other areas.

> **Dr. Maria Marinescu** Faculty of Chemistry, University of Bucharest, Romania

> > **1**

Section 1

Introduction to Chemistry

and Applications of

Benzimidazoles

Section 1
