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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2009-8-3
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pubmed:abstractText |
A series of (4-aminobutyn-1-yl)benzylamines were prepared and the SAR around three key areas: (1) the amine attached to the butynyl linker (R(3)R(4)N-); (2) the benzylamine moiety (R(1)R(2)N-); and (3) the point of attachment of the benzylamine group (R(1)R(2)N- in the ortho, meta, or para positions) was examined. One compound, 4-[3-(4-piperidin-1-yl-but-1-ynyl)-benzyl]-morpholine (9s) was chosen for further profiling and found to be a selective histamine H(3) antagonist with desirable drug-like properties. Ex vivo receptor occupancy studies established that 9s does occupy H(3) binding sites in the brain of rats after oral administration. Subcutaneous doses of 9s (10mg/kg) given during the natural sleep phase demonstrated robust wake-promoting effects.
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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 |
Oct
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pubmed:issn |
1768-3254
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pubmed:author |
pubmed-author:ApodacaRichardR,
pubmed-author:BonaventurePascalP,
pubmed-author:CarruthersNicholas INI,
pubmed-author:DolanJ SJS,
pubmed-author:DugovicChristineC,
pubmed-author:DvorakCurt ACA,
pubmed-author:DvorakLisa KLK,
pubmed-author:JablonowskiJill AJA,
pubmed-author:LovenbergTimothy WTW,
pubmed-author:MillerKirstenK,
pubmed-author:SheltonJonathanJ,
pubmed-author:VogtBB
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pubmed:issnType |
Electronic
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4098-106
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pubmed:meshHeading |
pubmed-meshheading:19524331-Animals,
pubmed-meshheading:19524331-Benzylamines,
pubmed-meshheading:19524331-Cell Line,
pubmed-meshheading:19524331-Diamines,
pubmed-meshheading:19524331-Histamine H3 Antagonists,
pubmed-meshheading:19524331-Humans,
pubmed-meshheading:19524331-Male,
pubmed-meshheading:19524331-Protein Binding,
pubmed-meshheading:19524331-Rats,
pubmed-meshheading:19524331-Rats, Sprague-Dawley,
pubmed-meshheading:19524331-Receptors, Histamine H3,
pubmed-meshheading:19524331-Sleep,
pubmed-meshheading:19524331-Structure-Activity Relationship,
pubmed-meshheading:19524331-Wakefulness
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pubmed:year |
2009
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pubmed:articleTitle |
Diamine-based human histamine H3 receptor antagonists: (4-aminobutyn-1-yl)benzylamines.
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pubmed:affiliation |
Johnson & Johnson Pharmaceutical Research & Development, LLC, San Diego, CA 92121, USA. cdvorak@its.jnj.com
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pubmed:publicationType |
Journal Article
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