Abstract:
:The gradual alignment with all of drug metabolism with all aspects of drug discovery and development has led to a complete realignment of the way the work is conducted. From a background of conducting bespoke in vivo studies much of the work is now in a high throughput screening mode. Large technological advances have been made, but the nature of drug metabolism processes, being multi-system and promiscuous means that much of the help provided to the medicinal chemistry is reactive rather than based on fundamental disposition structure-activity relationships. Lessons learned around the chemical and physicochemical properties more often associated with successfull discovery and development projects are only moderately helpful when the high value pharmacological targets of today only yield potent ligands outside of the boundaries these properties describe. Pivotal to the impact of these properties is the intrinsic permeability of a molecule, something not as widely recognised as perhaps it should be. Metabolic lability is still a problem and the tactics employed are unchanged in 20 years: attempt to lower lipophilicity, if it is too high overall or introduce blocking groups, particularly halogens, after identifying the sites of metabolism Perhaps the greatest success drug metabolism science has had over the last fifteen years is it's pivotal role in characterising drug-drug interactions and providing screening systems and computational models to investigate them. It still has many undeveloped areas of the science such as the role of metabolites in drug activity and why compounds vary in their extent of biliary excretion.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Smith DAdoi
10.2174/156802611794480909subject
Has Abstractpub_date
2011-01-01 00:00:00pages
467-81issue
4eissn
1568-0266issn
1873-4294pii
BSP/CTMC/E-Pub/-00035-11-5journal_volume
11pub_type
杂志文章,评审abstract::The dynamics of gene expression are regulated by histone acetylases (HATs) and histone deacetylases (HDACs) that control the acetylation state of lysine side chains of the histone proteins of chromatin. The catalytic activity of these two enzymes remodels chromatin to control gene expression without altering gene sequ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802609788085241
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666180410151518
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791268765
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608784535011
更新日期:2008-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150813150433
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Current topics in medicinal chemistry
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doi:10.2174/1568026620666200922115109
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607779941350
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2009-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666181224101744
更新日期:2018-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200710101307
更新日期:2020-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2002-09-01 00:00:00
abstract::The serotonin receptor subtype 5 HT(1A) was one of the first serotonin receptor subtypes pharmacologically characterized. Over the last twenty years the 5 HT(1A) receptor has been the object of intense research efforts as witnessed by the 5 HT(1A) acting drugs marketed as anxiolytics. In recent years, several new chem...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608785161385
更新日期:2008-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612799362922
更新日期:2012-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113139990139
更新日期:2013-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612805289890
更新日期:2012-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451591
更新日期:2004-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160216152324
更新日期:2016-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2018-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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更新日期:2013-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2003-01-01 00:00:00
abstract::G protein coupled receptors (GPCRs) are membrane proteins coupled with G proteins through which they transmit signals to the cytoplasm. Approximately 30% of pharmaceuticals target these receptors, even though crystal structures were scarce at the time. Furthermore, an additional 15% of GPCRs have yet to be exploited f...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract::Recent advances in DNA microarray technology have great impact on many areas of biomedical research and pharmacogenomics: discovering novel targets and genes, elucidating signatures of complex diseases, transcriptional profiling of models for diseases, and the development of individually optimized drugs based on diffe...
journal_title:Current topics in medicinal chemistry
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更新日期:2004-01-01 00:00:00
abstract::As the first stable tachysterol analogs, 14-epi-19-nortachysterol and its 2-substituted derivatives were synthesized using the Stille coupling reaction between the A-ring precursor (three vinylstannanes) and the CD-ring vinyl trifrate. Among them, the 2-methylidene group was hydrogenated with Wilkinson's catalyst regi...
journal_title:Current topics in medicinal chemistry
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更新日期:2014-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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更新日期:2012-01-01 00:00:00
abstract::Olefin metathesis has rapidly established itself as an essential tool in the synthetic chemist's armoury. The ease of operation and functional group tolerance that is obtained with the modern generation of catalysts makes the use of metathesis an extremely attractive option when preparing medicinally interesting molec...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802605775009757
更新日期:2005-01-01 00:00:00
abstract::Ischemic heart disease and cerebrovascular disease are the leading causes of death in the world. Surprisingly, these diseases are treated by relatively antiquated drugs. However, due to our improved understanding of the underlying pathology of these diseases, and a number of technological advances in tools for drug di...
journal_title:Current topics in medicinal chemistry
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更新日期:2001-06-01 00:00:00