Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

C-nucleosides have intrigued biologists and medicinal chemists since their discovery in 1950's. In that regard, C-nucleosides and their synthetic analogues have resulted in promising leads in drug design. Concurrently, advances in chemical syntheses have contributed to structural diversity and drug discovery efforts. Convergent and modular approaches to synthesis have garnered much attention in this regard. Among them nucleophilic substitution at C1' has seen wide applications providing flexibility in synthesis, good yields, the ability to maneuver stereochemistry as well as to incorporate structural modifications. In this review, we describe recent reports on the modular synthesis of C-nucleosides with a focus on D-ribonolactone and sugar modifications that have resulted in potent lead molecules.

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Recent Advances in the Synthesis of Piperazines: Focus on C–H Functionalization

Organics ◽

10.3390/org2040018 ◽

2021 ◽

Vol 2 (4) ◽

pp. 337-347

Author(s):

Carolina Durand ◽

Michal Szostak

Keyword(s):

Drug Discovery ◽

Medicinal Chemistry ◽

Structural Diversity ◽

Synthetic Methods ◽

Nitrogen Heterocycle ◽

Piperazine Ring ◽

The Third ◽

Recent Advances ◽

Made In

Piperazine ranks as the third most common nitrogen heterocycle in drug discovery, and it is the key component of several blockbuster drugs, such as Imatinib (also marketed as Gleevec) or Sildenafil, sold as Viagra. Despite its wide use in medicinal chemistry, the structural diversity of piperazines is limited, with about 80% of piperazine-containing drugs containing substituents only at the nitrogen positions. Recently, major advances have been made in the C–H functionalization of the carbon atoms of the piperazine ring. Herein, we present an overview of the recent synthetic methods to afford functionalized piperazines with a focus on C–H functionalization.

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Current Scenario in Structure and Ligand-Based Drug Design on Anti-colon Cancer Drugs

Current Pharmaceutical Design ◽

10.2174/1381612824666181114114513 ◽

2019 ◽

Vol 24 (32) ◽

pp. 3829-3841 ◽

Cited By ~ 1

Author(s):

Lakshmanan Loganathan ◽

Karthikeyan Muthusamy

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Anticancer Agent ◽

Computational Power ◽

Cancer Drugs ◽

Recent Advances ◽

Anti Cancer ◽

Drug Designing ◽

Current Scenario ◽

Molecular Modeling Studies

Worldwide, colorectal cancer takes up the third position in commonly detected cancer and fourth in cancer mortality. Recent progress in molecular modeling studies has led to significant success in drug discovery using structure and ligand-based methods. This study highlights aspects of the anticancer drug design. The structure and ligand-based drug design are discussed to investigate the molecular and quantum mechanics in anti-cancer drugs. Recent advances in anticancer agent identification driven by structural and molecular insights are presented. As a result, the recent advances in the field and the current scenario in drug designing of cancer drugs are discussed. This review provides information on how cancer drugs were formulated and identified using computational power by the drug discovery society.

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Recent Advances in Plasmepsin Medicinal Chemistry and Implications for Future Antimalarial Drug Discovery Efforts

Current Topics in Medicinal Chemistry ◽

10.2174/156802612799362959 ◽

2012 ◽

Vol 12 (5) ◽

pp. 445-455 ◽

Cited By ~ 47

Author(s):

Marvin J. Meyers ◽

Daniel E. Goldberg

Keyword(s):

Drug Discovery ◽

Antimalarial Drug ◽

Medicinal Chemistry ◽

Recent Advances

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Advances in antibiotic drug discovery: reducing the barriers for antibiotic development

Future Medicinal Chemistry ◽

10.4155/fmc-2020-0247 ◽

2020 ◽

Vol 12 (22) ◽

pp. 2067-2087

Author(s):

Kyle E Murphy ◽

Grace F Sloan ◽

Grace V Lawhern ◽

Grace E Volk ◽

Jacob T Shumate ◽

...

Keyword(s):

Public Health ◽

Multidrug Resistance ◽

Drug Discovery ◽

Natural Product ◽

Medicinal Chemistry ◽

Health Crisis ◽

Antibiotic Development ◽

Public Health Crisis ◽

Recent Advances ◽

Antibiotic Drug

Antibiotic drug discovery has been an essential field of research since the early 1900s, but the threat from infectious bacteria has only increased over the decades because of the emergence of widespread multidrug resistance. In this review, we discuss the recent advances in natural product, computational and medicinal chemistry that have reinvigorated the field of antibiotic drug discovery while giving perspective on how easily, both in cost and in expertise, these methods can be implemented by other researchers with the goal of increasing the number of scientists contributing to this public health crisis.

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Analogue-Based Drug Discovery: Contributions to Medicinal Chemistry Principles and Drug Design Strategies. Microtubule Stabilizers as a Case in Point (special topic article)

Chemistry International ◽

10.1515/ci.2012.34.5.24c ◽

2012 ◽

Vol 34 (5) ◽

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Medicinal Chemistry ◽

Special Topic ◽

Design Strategies

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Advances toward structure-based drug discovery for inflammasome targets

Journal of Experimental Medicine ◽

10.1084/jem.20211147 ◽

2021 ◽

Vol 219 (1) ◽

Author(s):

Li Wang ◽

Michael A. Crackower ◽

Hao Wu

Keyword(s):

Drug Discovery ◽

High Resolution ◽

Drug Design ◽

Structural Biology ◽

Drug Targets ◽

Unmet Need ◽

Structure Based Drug Design ◽

Important Family ◽

Recent Advances

Inflammasome proteins play an important role in many diseases of high unmet need, making them attractive drug targets. However, drug discovery for inflammasome proteins has been challenging in part due to the difficulty in solving high-resolution structures using cryo-EM or crystallography. Recent advances in the structural biology of NLRP3 and NLRP1 have provided the first set of data that proves a promise for structure-based drug design for this important family of targets.

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Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics

Molecules ◽

10.3390/molecules26247500 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7500

Author(s):

Marco Tutone ◽

Anna Maria Almerico

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Medicinal Chemistry ◽

Computational Approaches

To date, computational approaches have been recognized as a key component in drug design and discovery workflows [...]

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A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Molecules ◽

10.3390/molecules25081909 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1909 ◽

Cited By ~ 21

Author(s):

Nagaraju Kerru ◽

Lalitha Gummidi ◽

Suresh Maddila ◽

Kranthi Kumar Gangu ◽

Sreekantha B. Jonnalagadda

Keyword(s):

Drug Design ◽

Medicinal Chemistry ◽

Biological Activities ◽

Therapeutic Agents ◽

Biological Applications ◽

Valuable Source ◽

The Past ◽

Recent Advances ◽

Physiological Properties ◽

One Year

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.

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Analogue-based drug discovery: Contributions to medicinal chemistry principles and drug design strategies. Microtubule stabilizers as a case in point (Special Topic Article)

Pure and Applied Chemistry ◽

10.1351/pac-con-12-02-13 ◽

2012 ◽

Vol 84 (7) ◽

pp. 1479-1542 ◽

Cited By ~ 3

Author(s):

Mohammad H. El-Dakdouki ◽

Paul W. Erhardt

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Medicinal Chemistry ◽

Drug Distribution ◽

Therapeutic Agents ◽

Special Topic ◽

Design Strategies ◽

Basic Principles ◽

Research Activities ◽

Alternative Drug

The benefits of utilizing marketed drugs as starting points to discover new therapeutic agents have been well documented within the IUPAC series of books that bear the title Analogue-based Drug Discovery (ABDD). Not as clearly demonstrated, however, is that ABDD also contributes to the elaboration of new basic principles and alternative drug design strategies that are useful to the field of medicinal chemistry in general. After reviewing the ABDD programs that have evolved around the area of microtubule-stabilizing chemo-therapeutic agents, the present article delineates the associated research activities that additionally contributed to general strategies that can be useful for prodrug design, identifying pharmacophores, circumventing multidrug resistance (MDR), and achieving targeted drug distribution.

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