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Current opinion in drug discovery & development最新文献

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Cycloaddition chemistry of allenamides. 烯丙酰胺的环加成化学。
Current opinion in drug discovery & development Pub Date : 2010-01-01
Patricia E Standen, Marc C Kimber
{"title":"Cycloaddition chemistry of allenamides.","authors":"Patricia E Standen,&nbsp;Marc C Kimber","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Allenamides are electron-deficient equivalents of allenamines, which can participate in a range of cycloaddition reactions giving rise to novel heterocycles and diverse molecular architectures similar to those contained in natural products. This review summarizes some of the research conducted in this field, with particular reference to predicting the stereochemical outcomes of such transformations. The applications of allenamides in cycloaddition transformations are highlighted, providing insight into the potential utility of this under-used synthon.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"13 6","pages":"645-57"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29455831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug targeting: learning from toxin entry and trafficking in mammalian cells. 药物靶向:从哺乳动物细胞的毒素进入和贩运中学习。
Current opinion in drug discovery & development Pub Date : 2010-01-01
Robert A Spooner, Peter Watson
{"title":"Drug targeting: learning from toxin entry and trafficking in mammalian cells.","authors":"Robert A Spooner,&nbsp;Peter Watson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A significant number of therapeutic targets reside inside cells and intracellular organelles. Therapeutics therefore must be able to gain access to cellular compartments, and be able to interact specifically with a given molecule to exert a desired effect. Many naturally occurring toxins perform such targeting with apparent ease, making them excellent paradigms for the delivery of therapeutics to the cell interior. By studying the mechanisms of cell entry, trafficking and modes of toxicity of these model delivery vectors, researchers can decipher how cells transport both endogenous molecules and exogenously applied therapeutics inside cells. Perhaps more importantly, the exploitation of cell binding and trafficking motifs could allow a therapeutic to target specifically, traffic within and escape from cellular compartments; in addition, toxic domains can be used to disrupt cell function specifically for therapeutic purposes. This review provides an overview of recent developments in the understanding of toxin targeting and trafficking, and discusses how these developments could result in opportunities for the design of more specific and efficient systems for therapeutic targeting.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"13 1","pages":"86-95"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28624972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
hERG: protein trafficking and potential for therapy and drug side effects. hERG:蛋白质运输和潜在的治疗和药物副作用。
Current opinion in drug discovery & development Pub Date : 2010-01-01
Ingo Staudacher, Patrick A Schweizer, Hugo A Katus, Dierk Thomas
{"title":"hERG: protein trafficking and potential for therapy and drug side effects.","authors":"Ingo Staudacher,&nbsp;Patrick A Schweizer,&nbsp;Hugo A Katus,&nbsp;Dierk Thomas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Drug-induced QT interval prolongation is associated with torsade de pointes arrhythmia and sudden cardiac death. Acquired long QT syndrome poses a significant liability in pharmaceutical drug development, and has resulted in drugs being recalled from the market. This off-target property is caused primarily by the inhibition of cardiac hERG K+ currents. As a result, guidelines were established by The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) requiring the preclinical evaluation of direct hERG channel blockade and QT prolongation. This review discusses established, as well as newly discovered and currently under-recognized, pro-arrhythmic mechanisms that are associated with hERG protein trafficking. Defective hERG trafficking is a research area of intensive scientific activity, and the implementation of screening for this type of hERG liability should be considered in order to improve the risk assessment and detection of drug-associated cardiotoxicity in safety pharmacology.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"13 1","pages":"23-30"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28624574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interactions between traditional Chinese medicines and Western therapeutics. 中医与西医的相互作用。
Current opinion in drug discovery & development Pub Date : 2010-01-01
Elena Chan, Marisela Tan, Jianni Xin, Sucha Sudarsanam, Dale E Johnson
{"title":"Interactions between traditional Chinese medicines and Western therapeutics.","authors":"Elena Chan,&nbsp;Marisela Tan,&nbsp;Jianni Xin,&nbsp;Sucha Sudarsanam,&nbsp;Dale E Johnson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) is a holistic approach to health that attempts to bring the body, mind and spirit into harmony. TCM is an essential part of the healthcare system in several Asian countries, and is considered a complementary or alternative medical system in most Western countries. An integration of the traditional Chinese and Western systems of medicine has begun in multiple medical centers internationally, and there is increasing evidence that several herbs and combinations of herbs used in TCM impart important pharmacological effects. The number of databases and compilations of herbs, herbal formulations, phytochemical constituents and molecular targets is increasing, primarily because of the widespread use of TCM in combination with Western drugs. The continued popularity of herbal remedies worldwide suggests that evidence-based research in this field, as well as information regarding the potential efficacy and safety of phytochemical constituents in herbs and TCM formulations, are essential, particularly when TCM is used in combination with other drugs. Herb-drug interactions are similar to drug-drug interactions in terms of their effects on ADME properties. Improvements in the knowledge of the molecular targets and metabolic pathways, as well as of the synergistic and inhibitory effects associated with important phytochemicals from herbs and herbal formulations, will lead to the development of rational approaches for the safe combination of healthcare systems from different cultures.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"13 1","pages":"50-65"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28624577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microstructured reactors as tools for the intensification of pharmaceutical reactions and processes. 微结构反应器作为强化药物反应和过程的工具。
Current opinion in drug discovery & development Pub Date : 2009-11-01
Paul Chin, William S Barney, Bradford A Pindzola
{"title":"Microstructured reactors as tools for the intensification of pharmaceutical reactions and processes.","authors":"Paul Chin,&nbsp;William S Barney,&nbsp;Bradford A Pindzola","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Process intensification is a design philosophy that aims to reduce the cost and energy input into chemical processes, while simultaneously increasing yield and purity. Microstructured reactors have an important role to play in the implementation of this philosophy, as the transformation from batch to continuous processing and the heat and mass transfer characteristics of these reactors allows precise control of reaction time, temperature and mixing, leading to improvements in selectivity and conversion for organic reactions. This review highlights some of the remaining challenges to the widespread adoption of these reactors, and the progress being made toward overcoming these issues.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"12 6","pages":"848-61"},"PeriodicalIF":0.0,"publicationDate":"2009-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28492326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inventing and understanding catalytic, enantioselective reactions. 发明和理解催化、对映选择性反应。
Current opinion in drug discovery & development Pub Date : 2009-11-01
Masakatsu Shibasaki, Naoya Kumagai, Tomoyuki Mashiko
{"title":"Inventing and understanding catalytic, enantioselective reactions.","authors":"Masakatsu Shibasaki,&nbsp;Naoya Kumagai,&nbsp;Tomoyuki Mashiko","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This review summarizes recent advances in the development of efficient routes based on enantioselective catalysis for the synthesis of optically active therapeutic agents. Particular emphasis is placed on research that has streamlined the large-scale production of therapeutics for the treatment of type 2 diabetes mellitus (T2DM). Progress in the catalytic asymmetric hydrogenation and amination of unprotected substrates has enabled the establishment of concise synthetic routes for the production of the potent dipeptidyl peptidase 4 inhibitor sitagliptin, and the aldose reductase inhibitor ranirestat (Dainippon Sumimoto Pharma Co Ltd/Eisai Co Ltd/ Kyorin Pharmaceutical Co Ltd), both of which have attracted particular attention for their potential to treat T2DM and diabetic complications, respectively.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"12 6","pages":"862-75"},"PeriodicalIF":0.0,"publicationDate":"2009-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28492327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in the Nazarov cyclization. 纳扎罗夫环化的进展。
Current opinion in drug discovery & development Pub Date : 2009-11-01
Waka Nakanishi, Frederick G West
{"title":"Advances in the Nazarov cyclization.","authors":"Waka Nakanishi,&nbsp;Frederick G West","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Advances in synthetic methodology using the Nazarov reaction, particularly those published since 2005, are reviewed. Three principal subtopics are considered: stereocontrol (both relative and absolute), domino or cascade reactions initiated by the Nazarov cyclization (the 'interrupted Nazarov reaction'), and alternative substrates (including versions of the 'metallo-Nazarov' reaction).</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"12 6","pages":"732-51"},"PeriodicalIF":0.0,"publicationDate":"2009-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28492415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent progress in the total synthesis of indole alkaloids. 吲哚类生物碱全合成研究进展。
Current opinion in drug discovery & development Pub Date : 2009-11-01
Chitra R Edwankar, Rahul V Edwankar, Ojas A Namjoshi, Sundari K Rallapalli, Jie Yang, James M Cook
{"title":"Recent progress in the total synthesis of indole alkaloids.","authors":"Chitra R Edwankar,&nbsp;Rahul V Edwankar,&nbsp;Ojas A Namjoshi,&nbsp;Sundari K Rallapalli,&nbsp;Jie Yang,&nbsp;James M Cook","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This review describes the most recent synthetic routes directed toward the construction of structurally complex indole alkaloids, many syntheses of which contain the asymmetric Pictet-Spengler reaction as a key stereochemical step. A kinetic and conformational study of the epimerization of cis 1,2,3-trisubstituted tetrahydro-beta-carbolines into their trans counterparts is described, because this is key to complete asymmetric induction in the Pictet-Spengler reaction. A mechanistic study of the enzyme-catalyzed Pictet-Spengler reaction is also included. The total synthesis of the opioid agonist mitragynine, as well as corynantheidol and the oxindole alstonisine is presented. With regard to bisindole alkaloids, the total synthesis of the antileishmanial bisindoles accedinisine and N'-demethylaccedinisne is described.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"12 6","pages":"752-71"},"PeriodicalIF":0.0,"publicationDate":"2009-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28492320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biocatalytic routes to chiral amines and amino acids. 手性胺和氨基酸的生物催化途径。
Current opinion in drug discovery & development Pub Date : 2009-11-01
Vicente Gotor-Fernández, Vicente Gotor
{"title":"Biocatalytic routes to chiral amines and amino acids.","authors":"Vicente Gotor-Fernández,&nbsp;Vicente Gotor","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Biocatalysis is a well-known and well-established technology that allows clean and straightforward stereoselective transformations to be conducted under mild reaction conditions. Traditionally, hydrolases, oxidoreductases and lyases have been used for these transformations to give the final products in excellent yields and with a high level of enantiopurity. Particular attention has been focused on biocatalytic routes because of the increasing demand for economic and environmentally friendly processes for the manufacture of single enantiomer drugs and high added-value compounds by the industrial sector. Recent advances in the field of biotransformations applied to the production of chiral amines and amino acids are reviewed.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"12 6","pages":"784-97"},"PeriodicalIF":0.0,"publicationDate":"2009-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28492322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current parallel chemistry principles and practice: application to the discovery of biologically active molecules. 当前平行化学原理与实践:在发现生物活性分子中的应用。
Current opinion in drug discovery & development Pub Date : 2009-11-01
Paul J Edwards
{"title":"Current parallel chemistry principles and practice: application to the discovery of biologically active molecules.","authors":"Paul J Edwards","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This article describes the use of parallel chemistry techniques for drug discovery, based on publications from January 2006 to December 2008. Chemical libraries that yielded active compounds across a range of biological targets are presented, together with synthetic details when appropriate. Background information for the biological targets involved and any SAR that could be discerned within members of a library series also is discussed. New technological developments, as applied to library design and synthesis and, more generally, in the discovery of biologically active entities, are highlighted. In addition, the likely future directions for parallel chemistry in its ability to impact upon drug discovery are also presented.</p>","PeriodicalId":10809,"journal":{"name":"Current opinion in drug discovery & development","volume":"12 6","pages":"899-914"},"PeriodicalIF":0.0,"publicationDate":"2009-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28492877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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