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rdf:type |
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lifeskim:mentions |
umls-concept:C0017337,
umls-concept:C0027893,
umls-concept:C0086418,
umls-concept:C0243076,
umls-concept:C0392756,
umls-concept:C0439849,
umls-concept:C0445223,
umls-concept:C0597357,
umls-concept:C1280500,
umls-concept:C1449836,
umls-concept:C1510827,
umls-concept:C1514283,
umls-concept:C1552599,
umls-concept:C1704787,
umls-concept:C1880355
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pubmed:issue |
10
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pubmed:dateCreated |
2009-5-22
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pubmed:abstractText |
A series of novel imidazoline derivatives was synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Optimization of previously reported imidazoline leads, 1a and 1b, was attempted by introduction of substituents at the 5-position on the imidazoline ring and modification of the bis(4-fluorphenyl) moiety. A number of potent derivatives without human ether-a-go-go related gene potassium channel (hERG) activity were identified. Selected compounds, including 2a, were shown to have excellent brain and CSF permeability. Compound 2a displayed a suitable pharmacokinetic profile for chronic in vivo studies and potently inhibited D-Trp(34)NPY-induced acute food intake in rats. Oral administration of 2a resulted in a potent reduction of body weight in a diet-induced obese mouse model.
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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 |
May
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:AndoMakotoM,
pubmed-author:FujinoNaokoN,
pubmed-author:FukamiTakehiroT,
pubmed-author:GomoriAkiraA,
pubmed-author:IshiharaAkaneA,
pubmed-author:IshikawaShihoS,
pubmed-author:IwaasaHisashiH,
pubmed-author:JitsuokaMakotoM,
pubmed-author:KanataniAkioA,
pubmed-author:KitazawaHidefumiH,
pubmed-author:MashikoSatoshiS,
pubmed-author:MoriyaRyuichiR,
pubmed-author:NagaiKeitaK,
pubmed-author:OheTomoyukiT,
pubmed-author:SakurabaAyaA,
pubmed-author:SatoNagaakiN,
pubmed-author:TakahashiHirobumiH,
pubmed-author:TsugeHiroyasuH
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|
pubmed:issnType |
Electronic
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pubmed:day |
28
|
|
pubmed:volume |
52
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pubmed:owner |
NLM
|
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3385-96
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pubmed:meshHeading |
pubmed-meshheading:19459652-Animals,
pubmed-meshheading:19459652-Anti-Obesity Agents,
pubmed-meshheading:19459652-Brain,
pubmed-meshheading:19459652-Cerebrospinal Fluid,
pubmed-meshheading:19459652-Disease Models, Animal,
pubmed-meshheading:19459652-Drug Discovery,
pubmed-meshheading:19459652-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:19459652-Humans,
pubmed-meshheading:19459652-Imidazolines,
pubmed-meshheading:19459652-Obesity,
pubmed-meshheading:19459652-Pharmacokinetics,
pubmed-meshheading:19459652-Protein Binding,
pubmed-meshheading:19459652-Rats,
pubmed-meshheading:19459652-Receptors, Neuropeptide Y,
pubmed-meshheading:19459652-Structure-Activity Relationship,
pubmed-meshheading:19459652-Weight Loss
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pubmed:year |
2009
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pubmed:articleTitle |
Discovery of tetrasubstituted imidazolines as potent and selective neuropeptide Y Y5 receptor antagonists: reduced human ether-a-go-go related gene potassium channel binding affinity and potent antiobesity effect.
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pubmed:affiliation |
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Company, Ltd., Okubo 3, Tsukuba 300-2611, Japan. nagaaki_sato@merck.com
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pubmed:publicationType |
Journal Article
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