Download or read book Bioisosteres in Medicinal Chemistry written by Nathan Brown and published by John Wiley & Sons. This book was released on 2012-06-18 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written with the practicing medicinal chemist in mind, this is the first modern handbook to systematically address the topic of bioisosterism. As such, it provides a ready reference on the principles and methods of bioisosteric replacement as a key tool in preclinical drug development. The first part provides an overview of bioisosterism, classical bioisosteres and typical molecular interactions that need to be considered, while the second part describes a number of molecular databases as sources of bioisosteric identification and rationalization. The third part covers the four key methodologies for bioisostere identification and replacement: physicochemical properties, topology, shape, and overlays of protein-ligand crystal structures. In the final part, several real-world examples of bioisosterism in drug discovery projects are discussed. With its detailed descriptions of databases, methods and real-life case studies, this is tailor-made for busy industrial researchers with little time for reading, while remaining easily accessible to novice drug developers due to its systematic structure and introductory section.

Download or read book Resolution Pharmacology Innovative Therapeutic Approaches Based on the Biology of Resolution to Control Chronic Diseases of Western Societies written by Mauro Perretti and published by Frontiers Media SA. This book was released on 2019-11-04 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this eBook, we have grouped together 16 original contributions which have addressed the translational potential for therapeutics developed on the conceptual framework of the resolution of inflammation. The take home message of our effort, and the efforts of our colleagues who wrote these pieces, is that completely different drugs can be designed and modelled on the mediators and targets of resolution. By implementing this 180° shift in the way we plan the drug development programme (that is by focusing on agonists and/or promoting the actions of pro-resolution agonists) we can offer a fresh approach to the clinical management of chronic diseases that affect the modern society. With this series of articles we foresee the birth of Resolution Pharmacology. The 16 contributions presented herein confirm the broad relevance of pro-resolving physio-pharmacology with the description of pro-resolving mechanisms in distinct diseases, from atherosclerosis and heart infarct, to cystic fibrosis and diabetes. This testifies on one hand the fundamental role that inflammatory mechanisms play in virtually all pathological settings and, on the other hand, the great potential that a novel approach to anti-inflammatory therapy by exploiting resolution mediators and targets may have. Thus, while there is broad recognition that evidence-based interventions have transformed cardiovascular, inflammation and endocrine care, new therapies are still needed for growing numbers of patients with unmet needs. As an example, an estimated 17 million people world-wide die annually of cardiovascular diseases, particularly heart attacks and strokes. Cardiovascular diseases occur almost equally in men and women and are the leading cause of death and morbidity worldwide. It is estimated that only 1/1,000 compounds entering preclinical testing are then trialled in man and the actual cost of developing a new therapeutic into clinical practice has grown exponentially over the past two decades (estimated $1.2B). Over the last 20 years or more, scientists have appreciated the biology of the resolution of inflammation, which provides a new paradigm in our understanding of the inflammatory process with the appreciation of genetic, molecular and cellular mechanisms that are engaged to actively resolve inflammation. The ‘resolution of acute inflammation’ is enabled by counter-regulatory checkpoints to terminate the host reaction while at the same time promoting healing and repair. The potential of lipid mediators to enact pro-resolving effects in the context of cystic fibrosis is presented by Recchiuti et al., while Fredman reasons on the potential for these molecules in atherosclerosis. This resonates well with the contributions from Bäck and colleagues who have focused on pro-resolving receptors to offer vasculo-protection in intimal hyperplasia and more generally in cardiovascular disease. On the same vein is the scholar contribution of Leoni and Soehnlein who focus on heart disease, with Qin et al. presenting the latest findings on the effect of an Annexin A1-derived peptide in myocardial infarction. Hansen et al. and de Gaetano et al. bring in the complexity of diabetes and associated morbidity with a focus on specialised pro-resolving lipid mediators but also introducing the potential of dietary approaches. As the western diet favours disease, an omega-3 rich diet can lead to higher availability of lipid mediators to afford tissue protection if not reverting its pathological status. Docosahexaenoic acid and its bioactive derivatives are endowed with potent anti-nociceptive properties following bone fracture, as shown by Zhang et al. The broad relevance of the pharmacological approach reaches the skin with Resolvin D1 protecting against UV irradiation (Saito et al.). Reduced skin inflammation is also achieved with an Annexin A1 peptide that impacts on the outcome of heterologous transplantation (Lacerda et al.). Indeed, modulating the phenotype of immune cells can provide long lasting beneficial outcomes, as attained with CDK inhibitors (Cartwright et al.) and PI3K inhibitors in experimental gout (Galvao et al.). Such an effect is also achieved with a third group of pro-resolving therapeutics, the melanocortin receptor agonists, with important modulation of macrophage reactivity (Patruno et al.) with Spana et al., providing new pharmacology following selective activation of the MC1 receptor. Finally, Hopkin et al. discuss the potential for targeting immune cell trafficking as a way to control immune mediated diseases, bringing in not only pro-resolving mediator agonists, but also approaches to reduce chemo/cytokine gradients or modulating S1P and 11-beta hydroxysteroid dehydrogenase. Finally, we wish to highlight that this wealth of science has also bought to the forefront specific pro-resolving receptors (including FPR2/ALX, GPR32, ChemR23 and MC1), all G protein coupled receptors that are therefore amenable to pharmacological exploitation for drug discovery programmes. We see that not only agonists to the receptors can be developed, some of them modelled on the natural ligands (e.g. resolvins, lipoxins, Annexin A1-derived peptides or melanocortin peptides), but also that the creativity of this pharmacology can be attained through biased ligands and positive allosteric modulators. Deep knowledge of pro-resolving receptor biology and their cell-specific signalling can accelerate the generation of novel anti-inflammatory depicted on the resolution of inflammation. In conclusion, with this eBook, we propose time is ready to exploit the concepts of resolution and use its targets and mediators for the identification of better drugs to establish ‘Resolution Pharmacology’. We predict Resolution Pharmacology will represent an important innovation in the way common diseases will be treated in the next decades of this millennium.

Download or read book Structural Bioinformatics Applications in Preclinical Drug Discovery Process written by C. Gopi Mohan and published by Springer. This book was released on 2019-01-10 with total page 414 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews the advances and challenges of structure-based drug design in the preclinical drug discovery process, addressing various diseases, including malaria, tuberculosis and cancer. Written by internationally recognized researchers, this edited book discusses how the application of the various in-silico techniques, such as molecular docking, virtual screening, pharmacophore modeling, molecular dynamics simulations, and residue interaction networks offers insights into pharmacologically active novel molecular entities. It presents a clear concept of the molecular mechanism of different drug targets and explores methods to help understand drug resistance. In addition, it includes chapters dedicated to natural-product- derived medicines, combinatorial drug discovery, the CryoEM technique for structure-based drug design and big data in drug discovery. The book offers an invaluable resource for graduate and postgraduate students, as well as for researchers in academic and industrial laboratories working in the areas of chemoinformatics, medicinal and pharmaceutical chemistry and pharmacoinformatics.

Download or read book Pharmacoepigenetics written by Ramón Cacabelos and published by Academic Press. This book was released on 2019-06-04 with total page 986 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pharmacoepigenetics provides a comprehensive volume on the role of epigenetics and epigenomics in drug discovery and development, providing a detailed, but accessible, view of the field, from basic principles, to applications in disease therapeutics. Leading international researchers from across academia, clinical settings and the pharmaceutical industry discuss the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, and treatment, current epigenetic drugs, and the application of epigenetic procedures in drug development. Throughout the book, chapter authors offer a balanced and objective discussion of the future of pharmacoepigenetics and its crucial contribution to the growth of precision and personalized medicine. - Fully examines the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, treatment, current epigenetic drugs and the application of epigenetic procedures in drug development - Features chapter contributions from leading international researchers in academia, clinical settings and the pharmaceutical industry - Instructs researchers, students and clinicians on how to better interpret and employ pharmacoepigenetics in drug development, efficiency and safety - Provides a balanced and objective discussion of the future of pharmacoepigenetics and its crucial role in precision medicine

Download or read book Molecular Therapies of Cancer written by Georg F. Weber and published by Springer. This book was released on 2015-07-22 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Therapies of Cancer comprehensively covers the molecular mechanisms of anti-cancer drug actions in a comparably systematic fashion. While there is currently available a great deal of literature on anti-cancer drugs, books on the subject are often concoctions of invited review articles superficially connected to one another. There is a lack of comprehensive and systematic text on the topic of molecular therapies in cancer. A further deficit in the relevant literature is a progressive sub-specialization that typically limits textbooks on cancer drugs to cover either pharmacology or medicinal chemistry or signal transduction, rather than explaining molecular drug actions across all those areas; Molecular Therapies of Cancer fills this void. The book is divided into five sections: 1. Molecular Targeting of Cancer Cells; 2. Emerging and Alternative Treatment Modalities; 3. Molecular Targeting of Tumor-Host Interactions; 4. Anti-Cancer Drug Pharmacokinetics; and 5. Supportive Therapies.

Download or read book Antiepileptic Drug Discovery written by Alan Talevi and published by Humana. This book was released on 2016-09-24 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thorough volume delves into antiepileptic drug discovery with a comprehensive collection of innovative approaches for the development of antiepileptic therapies, focusing on novel molecular targets for antiepileptic drugs, computer-aided approaches for the identification of new drug candidates, and therapeutic strategies to overcome refractory epilepsy. The last section illustrates the potential benefits that network pharmacology and rational drug repurposing could bring to the antiepileptic drug discovery community. Written for the Methods in Pharmacology and Toxicology series, chapters include the kind of detailed description and implementation advice to ensure results in the laboratory. Authoritative and practical, Antiepileptic Drug Discovery: Novel Approaches aims to provide medicinal chemists, pharmacologists, and other researchers with the tools need to further explore the study of pharmacoresistant epilepsy and the discovery of new antiepileptic drugs.

Download or read book Green Approaches in Medicinal Chemistry for Sustainable Drug Design written by Bimal Banik and published by Elsevier. This book was released on 2020-03-27 with total page 1046 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extensive experimentation and high failure rates are a well-recognised downside to the drug discovery process, with the resultant high levels of inefficiency and waste producing a negative environmental impact. Sustainable and Green Approaches in Medicinal Chemistry reveals how medicinal and green chemistry can work together to directly address this issue. After providing essential context to the growth of green chemistry in relation to drug discovery in Part 1, the book goes on to identify a broad range of practical methods and synthesis techniques in Part 2. Part 3 reveals how medicinal chemistry techniques can be used to improve efficiency, mitigate failure and increase the environmental benignity of the entire drug discovery process, whilst Parts 4 and 5 discuss natural products and microwave-induced chemistry. Finally, the role of computers in drug discovery is explored in Part 6. - Identifies novel and cost effective green medicinal chemistry approaches for improved efficiency and sustainability - Reflects on techniques for a broad range of compounds and materials - Highlights sustainable and green chemistry pathways for molecular synthesis

Download or read book Detoxication Mechanisms written by Richard Tecwyn Williams and published by . This book was released on 1949 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Matrix Metalloproteinase Inhibitors in Cancer Therapy written by Neil J. Clendeninn and published by Springer Science & Business Media. This book was released on 2000-09-17 with total page 371 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

Download or read book Zinc in Human Nutrition written by Ananda Shiva Prasad and published by . This book was released on 1979 with total page 104 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Structure Description written by Lemont Burwell Kier and published by . This book was released on 1999 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: The electrotopological state is a new approach to defining key structural features of a molecule in drug design. Combining both electronic and topological attributes, the E-State index facilitates the development of a structure - activity model, the definition of a pharmacophore, and the search through a database for similar or dissimilar compounds. The background for the method, the concept of the intrinsic state, and the E-State index as a function of the atom or group within the field of all atoms in a molecule are all described in this primer for a new structure paradigm. Software on the bundled CD-ROM allows the reader to compute and display the E-State indices for molecules, while examples in the book illustrate strategies that can be used in drug research.

Download or read book HIV 1 Integrase written by Nouri Neamati and published by John Wiley & Sons. This book was released on 2011-08-10 with total page 710 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.

Download or read book Colloid and Interface Science in Pharmaceutical Research and Development written by Hiroyuki Ohshima and published by Elsevier. This book was released on 2014-07-23 with total page 533 pages. Available in PDF, EPUB and Kindle. Book excerpt: Colloid and Interface Science in Pharmaceutical Research and Development describes the role of colloid and surface chemistry in the pharmaceutical sciences. It gives a detailed account of colloid theory, and explains physicochemical properties of the colloidal-pharmaceutical systems, and the methods for their measurement. The book starts with fundamentals in Part I, covering fundamental aspects of colloid and interface sciences as applied to pharmaceutical sciences and thus should be suitable for teaching. Parts II and III treat applications and measurements, and they explains the application of these properties and their influence and use for the development of new drugs. - Provides a clear description of the fundamentals of colloid and interface science relevant to drug research and development - Explains the physicochemical/colloidal basis of pharmaceutical science - Lists modern experimental characterization techniques, provides analytical equations and explanations on analyzing the experimental data - Describes the most advanced techniques, AFM (Atomic Force Microscopy), SFA (Surface Force Apparatus) in detail

Download or read book Advances in Structure and Activity Relationship of Coumarin Derivatives written by Santhosh Penta and published by Academic Press. This book was released on 2015-08-07 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Structure and Activity Relationship of Coumarin Derivatives covers the structural behavior of various coumarin derivatives for various potential pharmaceutical applications. Based on substitution targeted for active sites, the book takes a rational approach for designing new and specific potent drugs, optimizing existing ones, and developing novel reactions. This focused primer describes the chemical structure and activity of coumarin derivatives to explore the effects of different substituents at specific positions, and their properties for effective bioactivity. - Accessible and current coverage of coumarin derivatives from structure to potential applications - Application of SAR technology to predict bioactivity of the derivatives based on its chemical structure - Information for researchers in medicinal chemistry, pharmaceutical sciences, and related fields

Download or read book Advances in Medicinal Chemistry written by B.E. Maryanoff and published by Elsevier. This book was released on 1999-04-01 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volume 4 of Advances in Medicinal Chemistry is comprised of six chapters on a wide range of topics in medicinal chemistry, including molecular modeling, structure-based drug design, organic synthesis, peptide conformational analysis, biological assessment, structure-activity correlation, and lead optimization. Chapter 1 presents an account about amino acid-based peptide mimetics corresponding to b-turn, loop, helical motifs in proteins as a probe of ligand-receptor and ligand-enzyme molecular interactions. Chapter 2 addresses new facets of the medicinal chemistry of the important anticancer drug Taxol® (paclitaxel). Chapter 3 relates an account of the search for new drugs for the treatment of malaria based on the natural product artemisinin. Chapter 4 applies computational chemistry to the evaluation of compound libraries for biological testing. Chapter 5 describes the construction of a 3-dimensional molecular model of the human thrombin receptor, the first protease-activated G-protein coupled receptor (PAR-1), as a means to explore the intermolecular contacts involved in agonist peptide recognition. Finally, Chapter 6 describes the research conducted at Merck on inhibitors of farnesyl transferase as a potential treatment for human cancers.

Download or read book Proteasome Inhibitors in Cancer Therapy written by Julian Adams and published by Springer Science & Business Media. This book was released on 2004-05-25 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.

Download or read book Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents written by Manju Rawat Singh and published by Academic Press. This book was released on 2020-04-07 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents provides sound data on the utility of biological and plant-based drugs and describes challenges faced in all aspects offering indispensable strategies to use in the development of bioactive medicines. Bioactive based medications are commonly used throughout the world and have been recognized by physicians and patients for their therapeutic efficacy. Bioactive formulations, including their subordinates and analogs, address 50% of all medicines in clinical practice. Novel bioactive medicine transporters can cure many disorders by both spatial and transitory approaches and have various justifications in medicinal potential. This book presents information on the utility of natural, plant, animal and bioengineered bioactive materials. It is a fundamental source of information and data for pharmacognosists, pharmaceutical analysts, drug transport scientists and pharmacologists working in bioactive medications. - Advances information on various bioactive based medications, their sources, clinical consequences and transport strategies - Illustrates diverse transport systems for bioactives and derivatives, novel techniques for formulations, targeting strategies and fundamental qualities of developed bioactive carriers, and their safety concerns and standardization - Discusses distinctive transport systems, stability, upgraded dissolvability, and enhanced bioavailability of bioactives