Preface

Heterocycles have diverse applications in various fields, such as pharmacy, medicine, dyestuffs, and polymers. As such, there is a need to continually upgrade the information related to heterocyclic compounds, which play a significant role in biochemical reactions in living cells. There is a whole range of heterocycles/fused heterocycles with one/two heteroatoms with a variety of applications. The momentum gained for the synthesis of new heterocycles testifies to their significance. The challenges in synthesizing new heterocycles and heterocycle properties that expand their use have stimulated research in the field. This book discusses various chemical strategies for the synthesis of the spectrum of heterocycles and their relevant applications in pharmaceuticals, agriculture, and material science. The green synthetic approach is an eco-friendly method to minimize/eliminate waste, decrease the consumption of energy, and promote the usage of green solvents. The book examines these green synthetic approaches for synthesizing the spectra of heterocyclic scaffolds. It includes eleven chapters.

Chapter 1, "Substituted Azoles as Non-Nucleoside Reverse Transcriptase Inhibitors Activity", discusses five-member azoles as anti-HIV medicines and, in particular, as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Chapter 2, "Pyrazole Scaffold: Strategies toward the Synthesis and Their Applications", addresses the broad-spectrum bioactivity of pyrazoles and the green synthetic methodology used for synthesizing them. Chapter 3, "Synthesis and Biological Applications of Thiazolidinone," discusses the synthesis of thiazolidinone derivatives and their biological effectiveness, including their anti-diabetic, antioxidant, and antibacterial activities. Chapter 4, "Synthetic Approaches for Pharmacologically Active Decorated Six-Membered Diazines", elaborates on the various synthetic techniques used to synthesize pharmacologically active decorated diazines, paying particular attention to non-fused substituted pyrimidines that have clinical applications. According to reports, diazines have numerous beneficial effects on human health, including antimetabolite, anticancer, antibacterial, anti-allergic, tyrosine kinase, antimicrobial, anti-inflammatory, analgesic, antihypertensive, antileishmanial, antituberculostatic, anticonvulsant, diuretic potassium-sparing, and anti-aggressive activities. Chapter 5, "Selected Imidazole Derivatives: Synthesis and X-Ray Crystal Structure – A Review", describes the synthesis and X-ray crystal structure analysis of selected significant imidazole derivatives, including DMDPIMH: 4,5-Dimethyl-1,2-diphenyl-1H-imidazole monohydrate; DMPPTI: 4,5-Dimethyl-2-phenyl-1-(p-tolyl)-1H-imidazole; FPDMMPI: 2-(4-Fluorophenyl)-4,5-dimethyl-1-(4- methylphenyl)-1H-imidazole; DMPDMPIHH: 1-(3,5-Dimethylphenyl)-4,5-dimethyl-2-phenyl-1H-imidazole hemihydrate; DMPFPDMI: 1-(3,5-Dimethylphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazole; FPMOPDMI: 2-(4-Fluorophenyl)-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole; DMOPFPDMI: 1-(3,5-Dimethoxyphenyl)-2-(4-fluorophenyl)-4,5-dimethyl-1H-imidazo; and FPTPI: 2-(4-Fluorophenyl)-1,4,5-triphenyl-1H-imidazole.

Chapter 6, "Synthesis of Five-Membered Heterocycles Using Water as a Solvent", discusses three typical five-membered heterocyclic compounds (furan, thiophene, and pyrrole) that can be synthesized using water as a solvent, as an aqueous medium has attracted tremendous interest from chemists for various organic synthesis. Chapter 7, "Current Development in the Synthesis of Benzimidazole-Quinoline Hybrid Analogues and their Biological Applications", presents synthetic methodologies for quinolone benzimidazole hybrid scaffolds and their potential pharmacological activity. Quinoline and benzimidazole are crucial scaffolding for drug discovery leads and have significance in medicinal chemistry. Chapter 8, "Construction of Biologically Active Five- and Six-Membered Fused Ring Pyrimidine Derivatives from 1,3-Diarylthiobarbituric Acids (DTBA)", highlights the synthesis and biological activity of certain fused pyrimidines, such as pyrazolo[3,4-d]pyrimidine-6-thiones; 5,7-diaryl-4-oxo-isoxazolo[5,4-d]pyrimidine-6-thiones; 5-oxo-pyrimido[4,5-d] pyrimidine-7-thiones; 2-thioxo-pyrano[2,3-d]pyrimidine-4-ones; pyrido[2,3-d] pyrimidines; quinazoline-4-oxo-2-thiones.Pyrimidines and fused pyrimidines have attracted a lot of attention because of the diverse range of biological functions they exhibit. Moreover, the pyrimidine ring with the thiourea linkage (-NH-C(S)-NH) is significant for pharmacological purposes because heterocyclic molecules with nitrogen and sulphur atoms were a major contributor to the development of medicine. Pyrimidine derivatives hold a special position in biological and medicinal chemistry because of the diverse spectrum of biological activities they display.

Chapter 9, "Synthetic Strategies and Biological Activities of 1,5-Disubstituted Pyrazoles and 2,5-Disubstituted Thiazoles", focuses on the strategies and various viewpoints on the synthesis of thiazoles and pyrazoles, including derivatives at the 2,4,5 positions and 1,5 positions, respectively. The chapter also explores their biological and therapeutic evaluations. Chapter 10, "Greener Approach towards the Synthesis of Nitrogen Based Heterocycles", covers the synthesis of N-based heterocycles using environmentally friendly and greener approaches. Chapter 11, "Recent Methods for Synthesis of Coumarin Derivatives and Their New Applications," discusses the synthesis of coumarins during which equivalent coumarin analogues are produced from substituted alkyne substrates.

Overall, this book offers an overview of synthetic methods for the synthesis of a variety of heterocycles, including green synthetic methods and heterocycle applications in a variety of fields.

> **Premlata Kumari** Associate Professor, Department of Chemistry, Sardar Vallabhbhai National Institute of Technology, Surat, India

> > **Amit B. Patel** Department of Chemistry, Government College Daman, Daman, India

**Chapter 1**

**Abstract**

Substituted Azoles as

*Rohit Singh and Avneet Kaur*

treatment of various diseases.

and biological application

**1. Introduction**

Non-Nucleoside Reverse

Transcriptase Inhibitors Activity

This Review article gives an overview of substituted azole based synthetic medicine and their significance application in treating various ailments. The chemical reactions of azoles with other heterocyclic compounds/chemical reagents produce a lot of new substituted molecules, which have plentiful biological actions and potential pharmaceutical applications. Azoles is considered a major class of heterocyclics and worldwide researchers have put great efforts in studying this nucleus in order to design and synthesize various new derived of imidazole and hybrid molecules with the identification of their significant role in many classes of drugs such as antiviral including anti-HIV. Azoles has inspiring molecular geometric structure that offers a suitable skeleton to build newer chemical entities which has encouraged medicinal chemists to design and synthesis of novel and effective molecule as potential therapeutic agents. However, there is an urgent need to study the mechanism of action at molecular level of several pharmacological actions resulting from azoles scaffold through modern methods to furnish safer and effective new molecules for the

**Keywords:** azoles, heterocyclic compounds, hybrid compounds, synthetic reactions

AIDS (Acquired immune deficiency syndrome) is the major cause of death which leads to pandemic worldwide. In today's scenario combination of Nucleoside reverse transcriptase inhibitors (NRTI), Non nucleoside reverse transcriptase inhibitors (NNRTI) and Protease inhibitors (PI). Highly active antiretroviral therapy (HAART) also called as anti retroviral therapy which is a combination of two or more combination of antiviral drugs become unsuccessful because of mutational change and virus getting resistant against anti viral drugs. Non nucleoside reverse transcriptase Inhibitors (NNRTI) binds to specific active site of reverse transcriptase of HIV are the important cascade of anti HIV-1 drugs mechanism. Molecular modeling studies of HIV enzyme complexes and chemical generation of second and third generation of
