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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2002-10-23
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pubmed:abstractText |
New tert-butyl, picolyl and fluorinated analogues of capromorelin (3), a short-acting growth hormone secretagogue (GHS), were prepared as part of a program to identify long-acting GHSs that increase 24-h plasma IGF-1 levels. Compounds 4c and 4d (ACD LogD values >or=2.9) displayed extended plasma elimination half-lives in dogs, primarily due to high volumes of distribution, but showed weak GH secretagogue activities in rats (ED(50)s>10 mg/kg). A less lipophilic derivative 4 (ACD LogD=1.6) exhibited a shorter canine half-life, but stimulated GH secretion in two animal species. Repeat oral dosing of 4 in dogs for 29 days (6 mg/kg) resulted in a significant down-regulation of the post dose GH response and a 60 and 40% increase in IGF-1 levels relative to pre-dose levels at the 8- and 24-h post dose time points. Compound 4 (CP-464709-18) has been selected as a development candidate for the treatment of frailty.
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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 |
Nov
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:CarpinoPhilip APA,
pubmed-author:Chidsey-FrinkKristin LKL,
pubmed-author:CookEwell RER,
pubmed-author:DaSilva-JardinePaul APA,
pubmed-author:DeNinnoShari LSL,
pubmed-author:DiBrinoJoseph NJN,
pubmed-author:HadaWilliam AWA,
pubmed-author:HadcockJohn RJR,
pubmed-author:InthavongsayJohnJ,
pubmed-author:LefkerBruce ABA,
pubmed-author:LewisSharon KSK,
pubmed-author:ManganoF MichaelFM,
pubmed-author:MullinsMichelle AMA,
pubmed-author:MurrayMarianne CMC,
pubmed-author:NgOichengO,
pubmed-author:NickersonDavid FDF,
pubmed-author:PanLydia CLC,
pubmed-author:PettersenJohn CJC,
pubmed-author:PirieChristine MCM,
pubmed-author:RaganJohn AJA,
pubmed-author:RoseColin RCR,
pubmed-author:TessDavid ADA,
pubmed-author:ThompsonDavid DDD,
pubmed-author:TolerSteven MSM,
pubmed-author:WilsonTheresa CTC,
pubmed-author:WrightAnn SAS,
pubmed-author:YuLiL,
pubmed-author:ZawistoskiMichael PMP
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3279-82
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12392732-Administration, Oral,
pubmed-meshheading:12392732-Animals,
pubmed-meshheading:12392732-Biological Availability,
pubmed-meshheading:12392732-Dogs,
pubmed-meshheading:12392732-Growth Hormone,
pubmed-meshheading:12392732-Growth Substances,
pubmed-meshheading:12392732-Half-Life,
pubmed-meshheading:12392732-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:12392732-Insulin-Like Growth Factor I,
pubmed-meshheading:12392732-Male,
pubmed-meshheading:12392732-Piperidines,
pubmed-meshheading:12392732-Pyrazoles,
pubmed-meshheading:12392732-Rats,
pubmed-meshheading:12392732-Rats, Wistar,
pubmed-meshheading:12392732-Structure-Activity Relationship
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pubmed:year |
2002
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pubmed:articleTitle |
Discovery and biological characterization of capromorelin analogues with extended half-lives.
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pubmed:affiliation |
Pfizer Global Research & Development, Groton Labs, MS8220-3004, Groton, CT 06340, USA. philip_a_carpino@groton.pfizer.com
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pubmed:publicationType |
Journal Article
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