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rdf:type |
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lifeskim:mentions |
umls-concept:C0037473,
umls-concept:C0205531,
umls-concept:C0220802,
umls-concept:C0226896,
umls-concept:C0231491,
umls-concept:C0442027,
umls-concept:C0470187,
umls-concept:C1451074,
umls-concept:C1527415,
umls-concept:C1880355,
umls-concept:C2714632
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pubmed:issue |
23
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pubmed:dateCreated |
2009-2-20
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pubmed:abstractText |
The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BozigianHaigH,
pubmed-author:ChenMiM,
pubmed-author:ChenTakungT,
pubmed-author:ChenYongshengY,
pubmed-author:GuoZhiqiangZ,
pubmed-author:HuangCharles QCQ,
pubmed-author:MadanAjayA,
pubmed-author:PontilloJosephJ,
pubmed-author:ReinhartGreg JGJ,
pubmed-author:RowbottomMartinM,
pubmed-author:SaundersJohnJ,
pubmed-author:StruthersR ScottRS,
pubmed-author:TucciFabio CFC,
pubmed-author:WadeWarrenW,
pubmed-author:WenJennyJ,
pubmed-author:WuDongpeiD,
pubmed-author:XXX,
pubmed-author:YewP RPR,
pubmed-author:ZhuYun-FeiYF
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7478-85
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pubmed:meshHeading |
pubmed-meshheading:19006286-Animals,
pubmed-meshheading:19006286-Caco-2 Cells,
pubmed-meshheading:19006286-Cytochrome P-450 CYP3A,
pubmed-meshheading:19006286-Drug Discovery,
pubmed-meshheading:19006286-Drug Evaluation, Preclinical,
pubmed-meshheading:19006286-Humans,
pubmed-meshheading:19006286-Hydrocarbons, Fluorinated,
pubmed-meshheading:19006286-Macaca fascicularis,
pubmed-meshheading:19006286-Male,
pubmed-meshheading:19006286-Microsomes, Liver,
pubmed-meshheading:19006286-Molecular Structure,
pubmed-meshheading:19006286-Pyrimidines,
pubmed-meshheading:19006286-Receptors, LHRH,
pubmed-meshheading:19006286-Stereoisomerism,
pubmed-meshheading:19006286-Structure-Activity Relationship,
pubmed-meshheading:19006286-Time Factors
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pubmed:year |
2008
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pubmed:articleTitle |
Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor.
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pubmed:affiliation |
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, California 92130, USA. cchen@neurocrine.com
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pubmed:publicationType |
Journal Article
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