|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
8
|
|
pubmed:dateCreated |
2009-4-16
|
|
pubmed:abstractText |
Tricyclic analogues were rationally designed as the high affinity niacin receptor G-protein-coupled receptor 109A (GPR109A) agonists by overlapping three lead structures. Various tricyclic anthranilide and cycloalkene carboxylic acid full agonists were discovered with excellent in vitro activity. Compound 2g displayed a good therapeutic index regarding free fatty acids (FFA) reduction and vasodilation effects in rats, with very weak cytochrome P450 2C8 (CYP2C8) and cytochrome P450 2C9 (CYP2C9) inhibition, and a good mouse pharmacokinetics (PK) profile.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anthranilic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloparaffins,
http://linkedlifedata.com/resource/pubmed/chemical/HCAR2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HCAR3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Heterocyclic Compounds, 3-Ring,
http://linkedlifedata.com/resource/pubmed/chemical/Hypolipidemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Niacin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
1520-4804
|
|
pubmed:author |
pubmed-author:CaiTian-QuanTQ,
pubmed-author:Carballo-JaneEsterE,
pubmed-author:ChenQingQ,
pubmed-author:ChengKangK,
pubmed-author:CollettiSteven LSL,
pubmed-author:DengQiaolinQ,
pubmed-author:DingFa-XiangFX,
pubmed-author:HammondMilton LML,
pubmed-author:HoltTom GTG,
pubmed-author:KrsmanovicMihajlo LML,
pubmed-author:RenNingN,
pubmed-author:ShenHong CHC,
pubmed-author:TaggartAndrew KAK,
pubmed-author:TataJames RJR,
pubmed-author:TongXinchunX,
pubmed-author:WatersM GerardMG,
pubmed-author:WilsieLarissa CLC,
pubmed-author:WolffMichael SMS,
pubmed-author:WuKenneth KKK,
pubmed-author:WuTsuei-JuTJ
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
23
|
|
pubmed:volume |
52
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2587-602
|
|
pubmed:dateRevised |
2011-11-3
|
|
pubmed:meshHeading |
pubmed-meshheading:19309152-Adipocytes,
pubmed-meshheading:19309152-Animals,
pubmed-meshheading:19309152-Anthranilic Acids,
pubmed-meshheading:19309152-CHO Cells,
pubmed-meshheading:19309152-Cricetinae,
pubmed-meshheading:19309152-Cricetulus,
pubmed-meshheading:19309152-Cycloparaffins,
pubmed-meshheading:19309152-Ear,
pubmed-meshheading:19309152-Flushing,
pubmed-meshheading:19309152-Heterocyclic Compounds, 3-Ring,
pubmed-meshheading:19309152-Humans,
pubmed-meshheading:19309152-Hypolipidemic Agents,
pubmed-meshheading:19309152-Lipolysis,
pubmed-meshheading:19309152-Male,
pubmed-meshheading:19309152-Mice,
pubmed-meshheading:19309152-Niacin,
pubmed-meshheading:19309152-Radioligand Assay,
pubmed-meshheading:19309152-Rats,
pubmed-meshheading:19309152-Receptors, G-Protein-Coupled,
pubmed-meshheading:19309152-Receptors, Nicotinic,
pubmed-meshheading:19309152-Structure-Activity Relationship,
pubmed-meshheading:19309152-Vasodilation
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
Discovery of novel tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats.
|
|
pubmed:affiliation |
Departments of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey 07065-0900, USA. hong_shen@merck.com
|
|
pubmed:publicationType |
Journal Article,
In Vitro
|
