Progress in medicinal chemistry最新文献

筛选
英文 中文
Medicinal chemistry by the numbers: the physicochemistry, thermodynamics and kinetics of modern drug design. 数字药物化学:现代药物设计的物理化学、热力学和动力学。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/s0079-6468(09)04801-2
Graham F Smith
{"title":"Medicinal chemistry by the numbers: the physicochemistry, thermodynamics and kinetics of modern drug design.","authors":"Graham F Smith","doi":"10.1016/s0079-6468(09)04801-2","DOIUrl":"https://doi.org/10.1016/s0079-6468(09)04801-2","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"48 ","pages":"1-29"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0079-6468(09)04801-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30163917","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: 33
Progress in the development of beta-secretase inhibitors for Alzheimer's disease. 阿尔茨海默病β -分泌酶抑制剂的研究进展。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/s0079-6468(09)04804-8
Jeffrey S Albert
{"title":"Progress in the development of beta-secretase inhibitors for Alzheimer's disease.","authors":"Jeffrey S Albert","doi":"10.1016/s0079-6468(09)04804-8","DOIUrl":"https://doi.org/10.1016/s0079-6468(09)04804-8","url":null,"abstract":"<p><p>Since the original identification of BACE in 1999 and until quite recently, BACE was often regarded as a \"difficult\" drug target, much as renin has proven to be. The reasons for this include the following. First, the long and shallow nature of the substrate binding pocket suggested that it would not be possible to identify small molecule drugs that could have adequate binding affinity. Second, functional groups that typically interact with the active site aspartates are usually highly polarized and, therefore, contribute to reduced CNS localization. Early BACE inhibitors were all designed using knowledge of the peptide substrates and usually contained some variation of a few well-known transition-state isosteres. While these had great impact on fundamental understanding of the enzyme structure and key interaction regions, they were very large, very polar, and had essentially no CNS availability. Continued progress by reducing the peptidic nature of these compounds resulted in incremental advances and has provided compounds that meet, or nearly meet, typical CNS drug-like criteria. The challenges associated with peptidic starting points inspired innovative new approaches to search for different starting points. Several groups employed high concentration screening (ligand concentration 100 microM and higher) to find weak hits after conventional screening (typically at 10 microM) failed to find more potent ones. Fragment-based methods have also been developed to identify even weaker hits (IC50 1 mM and greater). This was accomplished through the evolution and refinement of several detection methodologies including calorimetry, surface plasmon resonance, NMR, and crystallography. Coupled with detailed structural understanding of ligand-enzyme interactions and focus on maintaining ligand efficiency, these developments have resulted in several examples where potency was improved by 10,000-fold to afford compounds with IC50 values < 10 nM and promising drug-like characteristics. Together, all these efforts have afforded a diverse array of chemotypes as BACE inhibitors. Early work focused on improving BACE potency in isolated enzyme assays. However, most of these compounds showed potency reductions in cellular assays. Continued improvements in drug properties and in understanding of the physiologically relevant conditions have resulted in many compounds that show strong potency in both isolated and cellular assays. Several compounds have shown reduction of Abeta using rodent in-vivo models both peripherally and in the brain. Recently, one compound has demonstrated reduction of brain Abeta levels in a non-human primate. Phase I clinical trials were initiated on BACE inhibitor CTS-21166 from CoMentis in July of 2007. This compound derives from the earliest described peptidic inhibitors such as OM99-2 [58] but no details have been reported. In addition to strategies involving small molecule inhibitors of BACE and gamma-secretase to reduce Abeta levels","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"48 ","pages":"133-61"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0079-6468(09)04804-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30163920","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: 35
Progress in medicinal chemistry. Preface. 药物化学进展。前言。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/S0079-6468(08)00208-7
G Lawton, D R Witty
{"title":"Progress in medicinal chemistry. Preface.","authors":"G Lawton,&nbsp;D R Witty","doi":"10.1016/S0079-6468(08)00208-7","DOIUrl":"https://doi.org/10.1016/S0079-6468(08)00208-7","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"47 ","pages":"v-vi"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0079-6468(08)00208-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28079102","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
Advances in the design of 5-HT6 receptor ligands with therapeutic potential. 具有治疗潜力的5-HT6受体配体的设计进展。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/s0079-6468(09)04805-x
David Witty, Mahmood Ahmed, Tsu Tshen Chuang
{"title":"Advances in the design of 5-HT6 receptor ligands with therapeutic potential.","authors":"David Witty,&nbsp;Mahmood Ahmed,&nbsp;Tsu Tshen Chuang","doi":"10.1016/s0079-6468(09)04805-x","DOIUrl":"https://doi.org/10.1016/s0079-6468(09)04805-x","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"48 ","pages":"163-224"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0079-6468(09)04805-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30163921","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: 22
The adenosine A1 receptor and its ligands. 腺苷A1受体及其配体。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/S0079-6468(08)00204-X
Peter G Nell, Barbara Albrecht-Küpper
{"title":"The adenosine A1 receptor and its ligands.","authors":"Peter G Nell,&nbsp;Barbara Albrecht-Küpper","doi":"10.1016/S0079-6468(08)00204-X","DOIUrl":"https://doi.org/10.1016/S0079-6468(08)00204-X","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"47 ","pages":"163-201"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0079-6468(08)00204-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28079107","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: 24
Beginning of the 'numbers' era of medicinal chemistry. Preface. 药物化学的“数字”时代开始了。前言。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/S0079-6468(09)04810-3
G Lawton, D R Witty
{"title":"Beginning of the 'numbers' era of medicinal chemistry. Preface.","authors":"G Lawton,&nbsp;D R Witty","doi":"10.1016/S0079-6468(09)04810-3","DOIUrl":"https://doi.org/10.1016/S0079-6468(09)04810-3","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"48 ","pages":"v-vi"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0079-6468(09)04810-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28532165","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
Calcitonin gene-related peptide receptor antagonists for the treatment of migraine. 降钙素基因相关肽受体拮抗剂治疗偏头痛。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/S0079-6468(08)00201-4
Theresa M Williams, Christopher S Burgey, Christopher A Salvatore
{"title":"Calcitonin gene-related peptide receptor antagonists for the treatment of migraine.","authors":"Theresa M Williams,&nbsp;Christopher S Burgey,&nbsp;Christopher A Salvatore","doi":"10.1016/S0079-6468(08)00201-4","DOIUrl":"https://doi.org/10.1016/S0079-6468(08)00201-4","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"47 ","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0079-6468(08)00201-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28079104","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
Progress in the design and development of phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of chronic diseases. 用于治疗慢性疾病的磷酸肌苷3-激酶(PI3K)抑制剂的设计和开发进展。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/s0079-6468(09)04803-6
Stephen Shuttleworth, Franck Silva, Cyrille Tomassi, Alexander Cecil, Thomas Hill, Helen Rogers, Paul Townsend
{"title":"Progress in the design and development of phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of chronic diseases.","authors":"Stephen Shuttleworth,&nbsp;Franck Silva,&nbsp;Cyrille Tomassi,&nbsp;Alexander Cecil,&nbsp;Thomas Hill,&nbsp;Helen Rogers,&nbsp;Paul Townsend","doi":"10.1016/s0079-6468(09)04803-6","DOIUrl":"https://doi.org/10.1016/s0079-6468(09)04803-6","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"48 ","pages":"81-131"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0079-6468(09)04803-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30163919","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: 11
The identification of and rationale for drugs which act at the motilin receptor. 对运动素受体起作用的药物的鉴定和原理。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/s0079-6468(09)04802-4
Susan M Westaway, Gareth J Sanger
{"title":"The identification of and rationale for drugs which act at the motilin receptor.","authors":"Susan M Westaway,&nbsp;Gareth J Sanger","doi":"10.1016/s0079-6468(09)04802-4","DOIUrl":"https://doi.org/10.1016/s0079-6468(09)04802-4","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"48 ","pages":"31-80"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0079-6468(09)04802-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30163918","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: 18
PDE4 inhibitors - a review of the current field. PDE4抑制剂-当前领域综述。
Progress in medicinal chemistry Pub Date : 2009-01-01 DOI: 10.1016/S0079-6468(08)00202-6
Neil J Press, Katharine H Banner
{"title":"PDE4 inhibitors - a review of the current field.","authors":"Neil J Press,&nbsp;Katharine H Banner","doi":"10.1016/S0079-6468(08)00202-6","DOIUrl":"https://doi.org/10.1016/S0079-6468(08)00202-6","url":null,"abstract":"","PeriodicalId":20755,"journal":{"name":"Progress in medicinal chemistry","volume":"47 ","pages":"37-74"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0079-6468(08)00202-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28079105","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: 58
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书