Review: biologically active pyrazole derivatives
TL;DR: In this article, the authors summarize strategies to synthesize pyrazole derivatives and demonstrate that this class of compounds can be targeted for the discovery of new drugs and can be readily prepared owing to recent advances in synthetic medicinal chemistry.
Abstract: Nitrogen-containing heterocyclic compounds and their derivatives have historically been invaluable as a source of therapeutic agents. Pyrazole, which has two nitrogen atoms and aromatic character, provides diverse functionality and stereochemical complexity in a five-membered ring structure. In the past decade, studies have reported a growing body of data on different pyrazole derivatives and their innumerable physiological and pharmacological activities. In part, such studies attempted to reveal the wide range of drug-like properties of pyrazole derivatives along with their structure–activity relationships in order to create opportunities to harness the full potentials of these compounds. Here, we summarize strategies to synthesize pyrazole derivatives and demonstrate that this class of compounds can be targeted for the discovery of new drugs and can be readily prepared owing to recent advances in synthetic medicinal chemistry.
Citations
More filters
TL;DR: This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.
Abstract: The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.
587 citations
Additional excerpts
...No Structure Drug Name Activity 10 Molecules 2020, 25, x FOR PEER REVIEW 4 of 44 10 Fezolamine Antidepressant [35] Fezolamine Antidepressant [35] 11 Molecules 2020, 25, x FOR PEER REVIEW 5 of 44 Table 1....
[...]
...Fezolamine Antidepressant [35] Fezolamine Antidepressant [35]...
[...]
TL;DR: The different synthesis methods and the pharmacological properties of pyrazole derivatives developed by many scientists around the globe are highlighted.
Abstract: Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.
520 citations
TL;DR: A review of the photochemical and electrochemical applications of multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis can be found in this paper.
Abstract: We present here a review of the photochemical and electrochemical applications of multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis. MS-PCETs are redox mechanisms in which both an electron and a proton are exchanged together, often in a concerted elementary step. As such, MS-PCET can function as a non-classical mechanism for homolytic bond activation, providing opportunities to generate synthetically useful free radical intermediates directly from a wide variety of common organic functional groups. We present an introduction to MS-PCET and a practitioner's guide to reaction design, with an emphasis on the unique energetic and selectivity features that are characteristic of this reaction class. We then present chapters on oxidative N-H, O-H, S-H, and C-H bond homolysis methods, for the generation of the corresponding neutral radical species. Then, chapters for reductive PCET activations involving carbonyl, imine, other X═Y π-systems, and heteroarenes, where neutral ketyl, α-amino, and heteroarene-derived radicals can be generated. Finally, we present chapters on the applications of MS-PCET in asymmetric catalysis and in materials and device applications. Within each chapter, we subdivide by the functional group undergoing homolysis, and thereafter by the type of transformation being promoted. Methods published prior to the end of December 2020 are presented.
136 citations
TL;DR: In this article, a microwave assisted one-pot multicomponent reaction using MgO NPs as a heterogeneous, mild and reusable catalyst was proposed for the synthesis of steroidal pyridines.
Abstract: The present study reports a highly efficient and green synthetic route for the synthesis of steroidal pyridines. The synthetic methodology involves a microwave-assisted one-pot multicomponent reaction using MgO NPs as a heterogeneous, mild and reusable catalyst. The synthesized MgO NPs were characterized by FTIR, TGA/DTA and XRD analyses. The remarkable features of this protocol include simple operational procedure, shorter reaction profiles, mild reaction conditions, minimal chemical waste and economic viability. The recyclability of the catalyst and high yield of products make the proposed method a sustainable alternative.
107 citations
TL;DR: An overview of microwave assisted organic synthesis (MAOS) and its role in recent and pressing advancements for the synthesis of small and medium-sized nitrogen-containing heterocycles can be found in this article.
Abstract: Nitrogen containing heterocycles are of immense research interest because they are often found as naturally occurring bioactive compounds. The prominence of N-heterocycles makes it vital to develop methods to increase their synthetic efficiencies and probe the effects of their modifications on biological efficacy. Medicinal chemists have exploited microwave-assisted organic synthesis (MAOS) to facilitate the development of complex heterocyclic structures. MAOS is a growing synthetic methodology among medicinal chemists and has proven to be more efficient in terms of reaction yield, reaction time, product purity and environmental friendliness for many reactions when compared to conventional thermal methods for cycloaddition and selective functionalization. The importance of nitrogen containing ring systems in medicine cannot be understated, as such ring systems have shown to be applicable in compounds such as vitamins, herbicides, anti-fungal agents, anti-bacterial agents and anti-cancer agents, among other things. The significance of these applications has created an unprecedented need for more efficient synthetic methods. This review presents an overview of MAOS and its role in recent and pressing advancements for the synthesis of small- and medium-sized nitrogen containing heterocycles, including pyrroles, indoles, pyridines, pyrrolidines, imidazoles, pyrazoles, pyrazolines, lactams, and 1,2,3-triazoles, which are significant scaffolds for compounds with medicinal uses.
102 citations
References
More filters
TL;DR: Research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines, and the newly available control tools should allow a scaling up of control activities in priority areas.
Abstract: Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
2,150 citations
TL;DR: Analysis of recent trends reveals that the physical properties of molecules that are currently being synthesized in leading drug discovery companies differ significantly from those of recently discovered oral drugs and compounds in clinical development.
Abstract: The application of guidelines linked to the concept of drug-likeness, such as the 'rule of five', has gained wide acceptance as an approach to reduce attrition in drug discovery and development. However, despite this acceptance, analysis of recent trends reveals that the physical properties of molecules that are currently being synthesized in leading drug discovery companies differ significantly from those of recently discovered oral drugs and compounds in clinical development. The consequences of the marked increase in lipophilicity--the most important drug-like physical property--include a greater likelihood of lack of selectivity and attrition in drug development. Tackling the threat of compound-related toxicological attrition needs to move to the mainstream of medicinal chemistry decision-making.
1,954 citations
1,250 citations
TL;DR: The theoretical background for emissive metal complexes and the strategic design of the chelating C-linked 2-pyridylazolate ligands are elaborate, followed by their feasibility in functionalization and modification in an aim to fine-tune the chemical and photophysical properties.
Abstract: This article presents general concepts that have guided important developments in our recent research progress regarding room-temperature phosphorescent dyes and their potential applications. We first elaborate the theoretical background for emissive metal complexes and the strategic design of the chelating C-linked 2-pyridylazolate ligands, followed by their feasibility in functionalization and modification in an aim to fine-tune the chemical and photophysical properties. Subsequently, incorporation of 2-pyridylazolate chromophores is illustrated in the synthesis of the highly emissive, charge-neutral Os, Ru, Ir, and Pt complexes. Insights into their photophysical properties are gained from spectroscopy, relaxation dynamics, and theoretical approaches, from which the lowest-lying excited states, competitive radiative decay, and radiationless processes are then analyzed in detail. In view of applications, their potentials for OLEDs have been evaluated. The results, in combination with the fundamental basis, give a conceptual design contributed to the future advances in the field of OLEDs.
734 citations