Recent Developments in the Practical Application of Novel Carboxylic Acid Bioisosteres

2021 ◽  
Vol 28 ◽  
Author(s):  
Conor Horgan ◽  
Timothy P. O’ Sullivan
Keyword(s):  
Carboxylic Acid ◽  
Drug Design ◽  
Functional Group ◽  
Biological Membranes ◽  
Passive Diffusion ◽  
Practical Application ◽  
Physiochemical Properties ◽  
Advantages And Disadvantages ◽  
Modern Drug ◽  
Recent Developments

Background: The carboxylic acid is an important functional group which features in the pharmacophore of some 450 drugs. Unfortunately, some carboxylic acid-containing drugs have been withdrawn from market due to unforeseen toxicity issues. Other issues associated with the carboxylate moiety include reduced metabolic stability or limited passive diffusion across biological membranes. Medicinal chemists often turn to bioisosteres to circumvent such obstacles. Objective: The aim of this review is to provide a summary of the various applications of novel carboxylic acid bioisosteres which have appeared in the literature since 2013. Results: We have summarised the most recent developments in carboxylic acid bioisosterism. In particular, we focus on the changes in bioactivity, selectivity or physiochemical properties brought about by these substitutions, as well as the advantages and disadvantages of each isostere. Conclusion: The topics discussed herein highlight the continued interest in carboxylate bioisosteres. The development of novel carboxylic acid substitutes which display improved pharmacological profiles is testament to the innovation and creativity required to overcome the challenges faced in modern drug design.

scholarly journals Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4688
Author(s):  
Mootaz M. Salman ◽  
Zaid Al-Obaidi ◽  
Philip Kitchen ◽  
Andrea Loreto ◽  
Roslyn M. Bill ◽  
...  
Keyword(s):  
Drug Design ◽  
Neurodegenerative Diseases ◽  
Docking Studies ◽  
New Drugs ◽  
Computer Aided Drug Design ◽  
Biological Assays ◽  
Advantages And Disadvantages ◽  
Computer Aided ◽  
Research Challenge ◽  
The Cost

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.

THE SCOPE OF ACCREDITATION OF THE FORENSIC LABORATORY: THE CONCEPT AND PATTERNS OF CHANGE

2021 ◽  
Vol 14 (4) ◽  
pp. 340-344
Author(s):  
ELENA CHESNOKOVA ◽  
Keyword(s):  
Forensic Science ◽  
Research Work ◽  
Accreditation Body ◽  
Unfair Competition ◽  
Practical Application ◽  
International Standard ◽  
Advantages And Disadvantages ◽  
Flexible Scope ◽  
Calibration Laboratories

The purpose of the research work is to analyze the advantages and disadvantages of the «flexible» field of accreditation of forensic laboratories and the field of accreditation that has a rigid range. The development of standardization in forensic science, including the expansion of the number of forensic laboratories that build their activities in accordance with the requirements of the international standard GOST ISO/IEC 17025-2019 «General requirements for the competence of testing and calibration laboratories», encourages us to pay attention to this issue again. In the course of the study, the following conclusions were formulated. Insufficient clarity in defining the «flexible» scope of accreditation and differences in the understanding of its boundaries by the accreditation body, the forensic laboratory and the customer can lead to abuse by individual laboratories and the development of unfair competition. This argument in favor of abandoning the «flexible» field of accreditation for forensic laboratories seems to be much more weighty than the listed advantages of its practical application.

scholarly journals A Study Wireless Communication Domain

2011 ◽  
pp. 82-86
Author(s):  
Sangram Routray ◽  
Lalit M. Satapathy ◽  
Sanjib k. Nayak
Keyword(s):  
Wireless Communication ◽  
Embedded Systems ◽  
Short Range ◽  
Remote Access ◽  
Wireless Technologies ◽  
Advantages And Disadvantages ◽  
Recent Developments

Wireless communication seem destined to make a large and continuing impact on our lives. Recent developments in wireless technologies provide a new channel for implementation of embedded systems with remote access for mobile and non-mobile products and services. Several wireless technologies are available with their own advantages and disadvantages. This paper examines several available short-range wireless technologies and evaluates them for embedded systems.

scholarly journals Direct Transamidation Reactions: Mechanism and Recent Advances

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2382 ◽  
Author(s):  
Paola Acosta-Guzmán ◽  
Alejandra Mateus-Gómez ◽  
Diego Gamba-Sánchez
Keyword(s):  
Carboxylic Acid ◽  
Chemical Industry ◽  
Metal Catalysts ◽  
Direct Reaction ◽  
Valuable Alternative ◽  
Recent Advances ◽  
Other Substances ◽  
Recent Developments ◽  
Nitrogen Nucleophiles ◽  
Reactions Mechanism

Amides are undeniably some of the most important compounds in Nature and the chemical industry, being present in biomolecules, materials, pharmaceuticals and many other substances. Unfortunately, the traditional synthesis of amides suffers from some important drawbacks, principally the use of stoichiometric activators or the need to use highly reactive carboxylic acid derivatives. In recent years, the transamidation reaction has emerged as a valuable alternative to prepare amides. The reactivity of amides makes their direct reaction with nitrogen nucleophiles difficult; thus, the direct transamidation reaction needs a catalyst in order to activate the amide moiety and to promote the completion of the reaction because equilibrium is established. In this review, we present research on direct transamidation reactions ranging from studies of the mechanism to the recent developments of more applicable and versatile methodologies, emphasizing those reactions involving activation with metal catalysts.

An Introduction to the Basic Concepts in QSAR-Aided Drug Design

2015 ◽  
pp. 1-47 ◽  
Author(s):  
Maryam Hamzeh-Mivehroud ◽  
Babak Sokouti ◽  
Siavoush Dastmalchi
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Biological Activities ◽  
Model Development ◽  
Quantitative Structure Activity Relationship ◽  
Molecular Structures ◽  
New Drugs ◽  
Qsar Modeling ◽  
Qsar Studies ◽  
Modern Drug

The need for the development of new drugs to combat existing and newly identified conditions is unavoidable. One of the important tools used in the advanced drug development pipeline is computer-aided drug design. Traditionally, to find a drug many ligands were synthesized and evaluated for their effectiveness using suitable bioassays and if all other drug-likeness features were met, the candidate(s) would possibly reach the market. Although this approach is still in use in advanced format, computational methods are an indispensable component of modern drug development projects. One of the methods used from very early days of rationalizing the drug design approaches is Quantitative Structure-Activity Relationship (QSAR). This chapter overviews QSAR modeling steps by introducing molecular descriptors, mathematical model development for relating biological activities to molecular structures, and model validation. At the end, several successful cases where QSAR studies were used extensively are presented.

An Introduction to the Basic Concepts in QSAR-Aided Drug Design

Oncology ◽  
2017 ◽  
pp. 20-66
Author(s):  
Maryam Hamzeh-Mivehroud ◽  
Babak Sokouti ◽  
Siavoush Dastmalchi
Keyword(s):  
Drug Design ◽  
Drug Development ◽  
Biological Activities ◽  
Model Development ◽  
Quantitative Structure Activity Relationship ◽  
Molecular Structures ◽  
New Drugs ◽  
Qsar Modeling ◽  
Qsar Studies ◽  
Modern Drug

The need for the development of new drugs to combat existing and newly identified conditions is unavoidable. One of the important tools used in the advanced drug development pipeline is computer-aided drug design. Traditionally, to find a drug many ligands were synthesized and evaluated for their effectiveness using suitable bioassays and if all other drug-likeness features were met, the candidate(s) would possibly reach the market. Although this approach is still in use in advanced format, computational methods are an indispensable component of modern drug development projects. One of the methods used from very early days of rationalizing the drug design approaches is Quantitative Structure-Activity Relationship (QSAR). This chapter overviews QSAR modeling steps by introducing molecular descriptors, mathematical model development for relating biological activities to molecular structures, and model validation. At the end, several successful cases where QSAR studies were used extensively are presented.

Role of Molecular Docking in Computer-Aided Drug Design and Development

2016 ◽  
pp. 1-28
Author(s):  
Rahul Agarwal ◽  
Ashutosh Singh ◽  
Subhabrata Sen
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Protein Binding ◽  
Design And Development ◽  
Advantages And Disadvantages ◽  
Computer Aided ◽  
Drug Designing ◽  
Near Future

Molecular Docking is widely used in CADD (Computer-Aided Drug Designing), SBDD (Structure-Based Drug Designing) and LBDD (Ligand-Based Drug Designing). It is a method used to predict the binding orientation of one molecule with the other and used for any kind of molecule based on the interaction like, small drug molecule with its protein target, protein – protein binding or a DNA – protein binding. Docking is very much popular technique due to its reliable prediction properties. This book chapter will provide an overview of diverse docking methodologies present that are used in drug design and development. There will be discussion on several case studies, pertaining to each method, followed by advantages and disadvantages of the discussed methodology. It will typically aim professionals in the field of cheminformatics and bioinformatics, both in academia and in industry and aspiring scientists and students who want to take up this as a profession in the near future. We will conclude with our opinion on the effectiveness of this technology in the future of pharmaceutical industry.

Protein-Ligand Docking Methodologies and Its Application in Drug Discovery

2016 ◽  
pp. 196-219
Author(s):  
Sanchaita Rajkhowa ◽  
Ramesh C. Deka
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Drug Design ◽  
High Throughput Screening ◽  
Docking Studies ◽  
Stable Complex ◽  
Scoring Functions ◽  
Binding Modes ◽  
Structure Based Drug Design ◽  
Modern Drug

Molecular docking is a key tool in structural biology and computer-assisted drug design. Molecular docking is a method which predicts the preferred orientation of a ligand when bound in an active site to form a stable complex. It is the most common method used as a structure-based drug design. Here, the authors intend to discuss the various types of docking methods and their development and applications in modern drug discovery. The important basic theories such as sampling algorithm and scoring functions have been discussed briefly. The performances of the different available docking software have also been discussed. This chapter also includes some application examples of docking studies in modern drug discovery such as targeted drug delivery using carbon nanotubes, docking of nucleic acids to find the binding modes and a comparative study between high-throughput screening and structure-based virtual screening.

Sign in / Sign up

Export Citation Format

Share Document