The Fifth Element in Drug Design: Boron in Medicinal Chemistry

2013 ◽  
Vol 66 (10) ◽  
pp. 1118 ◽  
Author(s):  
Jan Kahlert ◽  
Christopher J. D. Austin ◽  
Michael Kassiou ◽  
Louis M. Rendina
Keyword(s):  
Pharmaceutical Industry ◽  
Drug Design ◽  
Boronic Acid ◽  
Medicinal Chemistry ◽  
Building Blocks ◽  
New Drugs ◽  
Great Promise ◽  
Research Groups ◽  
Innovative Drug ◽  
Boronic Acid Derivatives

The unique chemistry of boron allows for the utilisation of novel building-blocks which are not traditionally found in medicinal chemistry. The pharmaceutical industry has begun to exploit boronic acid derivatives as new drugs and several research groups are also exploring 1,2-azaborines and icosahedral boranes known as carboranes as boron-based structural motifs, with great promise for innovative drug design. Recent advances in the medicinal chemistry of these three important boron moieties are highlighted and illustrated with selected examples.

scholarly journals Rapid approach to complex boronic acids

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw4607 ◽  
Author(s):  
Constantinos G. Neochoritis ◽  
Shabnam Shaabani ◽  
Maryam Ahmadianmoghaddam ◽  
Tryfon Zarganes-Tzitzikas ◽  
Li Gao ◽  
...  
Keyword(s):  
Small Molecules ◽  
Boronic Acid ◽  
Multicomponent Reactions ◽  
Chemical Space ◽  
Building Blocks ◽  
Acid Synthesis ◽  
Success Rates ◽  
Boronic Acid Derivatives ◽  
Low Coverage ◽  
Target Synthesis

The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing–enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.

scholarly journals Emerging paradigms in anti-infective drug design

Parasitology ◽  
2014 ◽  
Vol 141 (1) ◽  
pp. 1-7 ◽  
Author(s):  
MICHAEL P. BARRETT ◽  
SIMON L. CROFT
Keyword(s):  
Drug Design ◽  
Medicinal Chemistry ◽  
Middle Part ◽  
The Body ◽  
New Drugs ◽  
British Society ◽  
Neglected Diseases ◽  
London School ◽  
Transfer Of Knowledge ◽  
Medical Needs

ABSTRACTThe need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled “Emerging Paradigms in Anti-Infective Drug Design” held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: “Target diseases and targets for drugs”, “Target based medicinal chemistry”, “Bioavailability and chemistry”, “Targeting intracellular microbes”, “Alternative approaches and models”, and “New anti-infectives – how do we get there?”This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.

Insights into newly approved drugs from a medicinal chemistry perspective

2021 ◽  
Vol 21 ◽  
Author(s):  
Elys Juliane Cardoso Lima ◽  
Renan Augusto Gomes ◽  
Evelin Fornari ◽  
Flavio da Silva Emery ◽  
Gustavo Henrique Goulart Trossini
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Drug Administration ◽  
Medicinal Chemistry ◽  
Food And Drug Administration ◽  
New Drugs ◽  
Design And Optimization ◽  
Continuous Evolution ◽  
Development Pipeline ◽  
Approved Drugs

: The development of new drugs is becoming notably harder each decade. To overcome the present pitfalls in the drug development pipeline, such as those related to potency, selectivity, or absorption, distribution, metabolism, excretion and toxicity properties, medicinal chemistry strategies need to be in continuous evolution and need to become even more multidisciplinary. In this review, we present how structure-based, ligand-based, and fragment-based drug design (SBDD, LBDD, and FBDD, respectively) and their respective techniques were used for the design and optimization of successful cases of new molecular entities (NMEs) approved by the Food and Drug Administration (FDA).

Recent Neglected Drug Design Studies

2021 ◽  
Vol 21 ◽  
Author(s):  
Natália Ferreira de Sousa ◽  
Luciana Scotti ◽  
Gabriela Cristina Soares Rodrigues ◽  
Érika Paiva de Moura ◽  
Renata Priscila Barros Costa Barros ◽  
...  
Keyword(s):  
Drug Design ◽  
Organic Synthesis ◽  
Medicinal Chemistry ◽  
New Drugs ◽  
Experimental Methodology ◽  
Neglected Diseases ◽  
Basic Sanitation ◽  
Molecular Hybrids ◽  
Therapeutic Alternatives ◽  
Selection Of

Background: Neglected diseases require special attention when looking for new therapeutic alternatives, as these are diseases of extreme complexity and severity that affect populations belonging to lower social classes who are lacking access to basic rights such as basic sanitation. Introduction: Among the alternatives available for obtaining new drugs is Medicinal Chemistry, which is responsible for the discovery, identification, invention and preparation of prototypes. In this perspective, the present work aims to make a bibliographic review on the recent studies of Medicinal Chemistry applied to neglected diseases. Method: A literature review was carried out by searching the “Web of Sciences” database, including recent articles published in the Neglected Drug Design. Results: In general, it was noticed that the most studied neglected diseases corresponded to Chagas disease and leishmaniasis, with studies on organic synthesis, optimization of structures and molecular hybrids being the most used strategies. It is also worth mentioning the growing number of computationally developed studies, providing speed and optimization of costs in the procurement process. Conclusion: The CADD approach and organic synthesis studies, when applied in the area of Medicinal Chemistry proved to be important in the research and discovery of drugs for Neglected Diseases, since the planning of the experimental methodology used to obtain it, as well as in the selection of compounds with greater activity potential.

Antiplatelet Therapy in Acute Coronary Syndromes

2010 ◽  
Vol 6 (1) ◽  
pp. 58
Author(s):  
Sasha Koul ◽  
David Erlinge ◽  
◽  
Keyword(s):  
Platelet Function ◽  
Acute Coronary Syndromes ◽  
New Drugs ◽  
Antiplatelet Drugs ◽  
Bleeding Complications ◽  
Great Promise ◽  
Mortality Data ◽  
Poor Responders ◽  
Coronary Syndromes

Drugs inhibiting platelet function play a major role in the treatment of acute coronary syndromes (ACS). The first drug used, which is still considered the cornerstone of therapy today, is aspirin. Although very impressive in acutely decreasing rates of myocardial infarction as well as death, long-term data are scarce, despite our current recommendation for lifelong aspirin. The thienopyridines, most notably clopidogrel, are the next line of antiplatelet drugs. Well-documented data support the usage of clopidogrel for non-STEMI-ACS (NSTE-ACS). Although positive mortality data exist regarding clopidogrel and STEMI patients in a medically treated population, including thrombolysis, no larger amounts of randomised data exist in a primary PCI setting. Poor responders to aspirin and/or clopidogrel are a clinical problem, with these individuals constituting a higherrisk group for recurrent ischaemic events. Whereas very little can be done regarding aspirin resistance, clopidogrel resistance might be diminished by increasing the dosage or changing to more potent and newer-generation antiplatelet drugs. The role of glycoprotein IIb/IIIa inhibitors has diminished drastically and instead paved the way for thrombin antagonists (bivalirudin), which have fewer bleeding complications with resulting better long-term mortality. Novel adenosine diphosphate (ADP)-receptor blockers such as prasugrel and ticagrelor have shown increased efficacy over clopidogrel and hold great promise for the future. However, not all patients may benefit from these new drugs and economic constraints may also limit their use. Platelet function tests could possibly help in identifying risk groups in need of stronger platelet inhibition.

Cascade CuH-Catalyzed Conversion of Alkynes to Enantioenriched 1,1-Disubstituted Products

2019 ◽  
Author(s):  
De-Wei Gao ◽  
Yang Gao ◽  
Huiling Shao ◽  
Tian-Zhang Qiao ◽  
Xin Wang ◽  
...  
Keyword(s):  
Organic Synthesis ◽  
Medicinal Chemistry ◽  
Proteasome Inhibitors ◽  
Building Blocks ◽  
Unique Role ◽  
Efficient Strategy ◽  
Carbon Centers ◽  
Rapid Access ◽  
Cascade Catalysis ◽  
Privileged Scaffolds

Enantioenriched <i>α</i>-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalyzed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centers. In contrast, applying CuH cascade catalysis to achieve reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize <i>α</i>-aminoboronates <i>via </i>CuH-catalyzed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product in favor of alternative homodifunctionalized, 1,2-heterodifunctionalized, or reductively monofunctionalized byproducts, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.<br>

Synthesis and Biological Activity of Hydrazones and Derivatives: A Review

2020 ◽  
Vol 20 (5) ◽  
pp. 342-368 ◽  
Author(s):  
Juliana de Oliveira Carneiro Brum ◽  
Tanos Celmar Costa França ◽  
Steven R. LaPlante ◽  
José Daniel Figueroa Villar
Keyword(s):  
Biological Activity ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
New Drugs ◽  
New Drug ◽  
Cancer Inflammation

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer’s, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.

scholarly journals PyroMEMS as Future Technological Building Blocks for Advanced Microenergetic Systems

Micromachines ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 118
Author(s):  
Jean-Laurent Pouchairet ◽  
Carole Rossi
Keyword(s):  
Building Block ◽  
Building Blocks ◽  
Small Scale ◽  
Technological Evolution ◽  
Research Groups ◽  
Function Block ◽  
The Past ◽  
New Methods ◽  
Safety And Reliability ◽  
Electronically Controllable

For the past two decades, many research groups have investigated new methods for reducing the size and cost of safe and arm-fire systems, while also improving their safety and reliability, through batch processing. Simultaneously, micro- and nanotechnology advancements regarding nanothermite materials have enabled the production of a key technological building block: pyrotechnical microsystems (pyroMEMS). This building block simply consists of microscale electric initiators with a thin thermite layer as the ignition charge. This microscale to millimeter-scale addressable pyroMEMS enables the integration of intelligence into centimeter-scale pyrotechnical systems. To illustrate this technological evolution, we hereby present the development of a smart infrared (IR) electronically controllable flare consisting of three distinct components: (1) a controllable pyrotechnical ejection block comprising three independently addressable small-scale propellers, all integrated into a one-piece molded and interconnected device, (2) a terminal function block comprising a structured IR pyrotechnical loaf coupled with a microinitiation stage integrating low-energy addressable pyroMEMS, and (3) a connected, autonomous, STANAG 4187 compliant, electronic sensor arming and firing block.

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