Burger's Medicinal Chemistry and Drug Discovery最新文献_第7页

New Strategies for Natural Products Lead Generation 新战略的天然产品领先一代

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC116

G. Carter, V. Bernan, F. Koehn

{"title":"New Strategies for Natural Products Lead Generation","authors":"G. Carter, V. Bernan, F. Koehn","doi":"10.1002/0471266949.BMC116","DOIUrl":"https://doi.org/10.1002/0471266949.BMC116","url":null,"abstract":"Microbial sources of natural products are increasingly valued for their chemical diversity and access to biosynthetic pathways. It appears that an incredible repository of untapped microbial life and associated chemical diversity remain to be exploited. Molecular techniques such as “metagenomics” are beginning to provide access to cryptic biosynthetic pathways, which are also revealing new chemistry. Refined libraries of natural products with well-characterized components provide enhanced value as screening sources. These libraries continue to provide new chemical entities that inform biological processes and provide leads for therapeutic agents. There is a renaissance of phenotypic screening that promises to uncover numerous new links between secondary metabolites and their roles in biology. Genomic methods are growing in value as our understanding of biosynthetic processes at the molecular level expands. Screening of DNA sequences for pathways that yield particular chemistries is now a reality for certain types of biosynthetic processes, especially type I polyketide synthases and nonribosomally produced peptides. \u0000 \u0000 \u0000Keywords: \u0000 \u0000biodiversity; \u0000marine actinomycetes; \u0000microbial genomics; \u0000natural products lead generation; \u0000natural products libraries; \u0000screening; \u0000secondary metabolites","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"81 1","pages":"191-220"},"PeriodicalIF":0.0,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73039116","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

CCR5 Antagonists: Small‐Molecule Inhibitors For Blocking HIV‐1 Entry CCR5拮抗剂:阻断HIV - 1进入的小分子抑制剂

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC230

J. Tagat

引用次数: 0

Immunosuppressive Agents for the Prevention of Transplantation Rejection 免疫抑制剂预防移植排斥反应

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC206

W. Pitts

引用次数: 0

Large‐Scale Synthesis 大尺度应承担的合成

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC032.PUB2

Frank Gupton

{"title":"Large‐Scale Synthesis","authors":"Frank Gupton","doi":"10.1002/0471266949.BMC032.PUB2","DOIUrl":"https://doi.org/10.1002/0471266949.BMC032.PUB2","url":null,"abstract":"The capability to fulfill drug substance requirements to support the various elements of pharmaceutical development is an essential component of the overall drug development process. The preparation of bulk materials for toxicology, formulation development, and clinical supplies can represent a significant challenge, depending on such factors as the molecular complexity of the drug candidate, the quantities of materials required, and the state of development of the synthetic process. As a drug candidate proceeds through the various stages of drug development and into commercial launch, the challenge of process development is to ensure the uninterrupted supply of drug substance without compromising the ability to ultimately supply a commercially viable chemical process. This chapter provides a general overview of the issues and requirements associated with the development and scale-up of chemical processes for bulk active drug substances. An account of the nevirapine process development efforts at Boehringer Ingelheim is also provided as an example of the evolution of a chemical process from the initial efforts in medicinal chemistry to commercial-scale operations. \u0000 \u0000 \u0000Keywords: \u0000 \u0000active pharmaceutical ingredients; \u0000drug development process; \u0000in-process controls; \u0000process chemist; \u0000process development","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"1 1","pages":"1-24"},"PeriodicalIF":0.0,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78163415","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: 19

Cost‐Effectiveness Analyses Throughout the Drug Development Life Cycle 整个药物开发生命周期的成本效益分析

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC161

R. Arnold

引用次数: 0

Atherosclerosis II: HDL Elevation 动脉粥样硬化II: HDL升高

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC193

Amjad Ali, J. A. Hunt, P. Sinclair

引用次数: 1

Physicochemical Characterization and Oral Dosage Form Selection Based on the Biopharmaceutics Classification System 基于生物制药分类系统的理化特性及口服剂型选择

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC038.PUB2

G. Amidon, Xiaorong He, M. Hageman

{"title":"Physicochemical Characterization and Oral Dosage Form Selection Based on the Biopharmaceutics Classification System","authors":"G. Amidon, Xiaorong He, M. Hageman","doi":"10.1002/0471266949.BMC038.PUB2","DOIUrl":"https://doi.org/10.1002/0471266949.BMC038.PUB2","url":null,"abstract":"Identifying an active lead molecule, selecting a viable drug candidate and developing a marketable product are profoundly influenced by molecular properties and dosage form design. This chapter discusses the importance of a molecule's physicochemical properties and the link with oral dosage form design strategies. The Biopharmaceutics Classification Scheme (BCS) is used to identify oral dosage form options that have the best chance of overcoming drug delivery problems. Physicochemical characterization not only can guide the selection of formulation strategies but also, if incorporated into the lead selection process, can influence analog selection and lead optimization. The end result of considering physicochemical properties is to reduce the risk of failure by facilitating the identification of appropriate dosage form design options and, at the same time, allow discovery chemists to maximize chances of identifying commercially viable leads. \u0000 \u0000 \u0000Keywords: \u0000 \u0000absorption; \u0000bioavailability; \u0000formulation; \u0000permeability; \u0000solid forms; \u0000solubility; \u0000stability","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"38 1","pages":"25-62"},"PeriodicalIF":0.0,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86071485","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: 1

Therapeutic and Diagnostic Agents for Parkinson’s Disease 帕金森病的治疗和诊断试剂

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC105.PUB2

R. Booth, J. Neumeyer, R. Baldessarini

{"title":"Therapeutic and Diagnostic Agents for Parkinson’s Disease","authors":"R. Booth, J. Neumeyer, R. Baldessarini","doi":"10.1002/0471266949.BMC105.PUB2","DOIUrl":"https://doi.org/10.1002/0471266949.BMC105.PUB2","url":null,"abstract":"This chapter considers the biology and medical chemistry-based treatment of Parkinson’s disease, the second most common of the major neurodegenerative neuropsychiatric disorders. It surveys basic clinical features, neuropathology, and etiological theories based on genetics, maturational and oxidative-metabolic degenerative processes, and environmental neurotoxins including MPTP. Treatments reviewed include l-dopa as a replacement therapy, direct dopaminergic agonists and their structure-activity relationships, and agents that potentiate dopamine by preventing the metabolism of dopa or dopamine by peripheral aromatic amino acid decarboxylase, catechol-O-methyltransferase, or monoamineoxidase. Drugs acting on nondopaminergic systems considered include anticholinergic, adenosine agonist, glutamate antagonist, and serotonin agonist agents. Agents useful for the diagnosis of Parkinson’s disease and monitoring progression of the disease include radioactive dopa and dopamine transporter labeling agents for use in brain imaging. Finally, future directions of efforts to improve the treatment of Parkinson’s disease are considered, with an emphasis on the continued central importance of medicinal chemistry. \u0000 \u0000 \u0000Keywords: \u0000 \u0000adenosine antagonists; \u0000basal ganglia; \u0000COMT inhibitors; \u0000decarboxylase inhibitors; \u0000dopamine; \u0000dopamine agonists; \u0000D1 agonists; \u0000D2 agonists; \u0000ergolines; \u0000glutamate antagonists; \u0000levodopa; \u0000MAO inhibitors; \u0000MPTP; \u0000neurodegeneration; \u0000oxidation; \u0000Parkinson’s disease; \u0000parkinsonism; \u0000pramipexole; \u0000radiodiagnostic agents; \u0000receptors; \u0000ropinirole; \u0000serotonin agonists","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"75 1","pages":"529-568"},"PeriodicalIF":0.0,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86126151","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: 2

Crystallographic Survey of Albumin Drug Interaction and Preliminary Applications in Cancer Chemotherapy 白蛋白药物相互作用的晶体学研究及其在肿瘤化疗中的初步应用

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC166

D. Carter

{"title":"Crystallographic Survey of Albumin Drug Interaction and Preliminary Applications in Cancer Chemotherapy","authors":"D. Carter","doi":"10.1002/0471266949.BMC166","DOIUrl":"https://doi.org/10.1002/0471266949.BMC166","url":null,"abstract":"An overview of the results of a comprehensive crystallographic structural survey of drug binding to human albumin at atomic resolution is presented. More than 350 complexes were examined, ultimately producing more than 200 structures with representatives in every major therapeutic category. The survey indicated 12 independent drug-binding locations dominated by the three sites located within subdomains IIA, IIIA, and IB. Site IB, the most structurally accommodating site on albumin, revealed a propensity for large heterocyclic ligands and showed the highest overall binding frequency at 49%. Details of IB ligand-binding chemistry are presented for several ligands including the camptothecin, anthracyclin, and podophylotoxin families of oncology drugs. The results from the survey were used to establish a therapeutic drug combination approach that favorably alters the albumin-based pharmacokinetics of several highly cytotoxic oncology drugs leading to marked improvements in safety and efficacy. Examples are presented for selected applications of improving the albumin-based pharmacokinetics of this information in drug development to improving the safety and efficacy of highly cytotoxic drugs for several important families of oncology drugs. \u0000 \u0000 \u0000Keywords: \u0000 \u0000crystallography; \u0000drug binding; \u0000oncology; \u0000serum albumin; \u0000survey","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"332 1","pages":"437-468"},"PeriodicalIF":0.0,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78920704","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: 15

Medicinal Chemistry Approaches for Multitarget Drugs 多靶点药物的药物化学方法

Burger's Medicinal Chemistry and Drug Discovery Pub Date : 2010-09-15 DOI: 10.1002/0471266949.BMC124

R. Morphy, Z. Rankovic

引用次数: 4