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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2007-1-18
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pubmed:abstractText |
A series of biphenylaminocyclopropane carboxamide based bradykinin B1 receptor antagonists has been developed that possesses good pharmacokinetic properties and is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in the lead structure with polyhaloacetamides, particularly a trifluoroacetamide, significantly reduced P-glycoprotein mediated efflux for the series proved essential. One of these novel bradykinin B1 antagonists (13b) also exhibited suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for further development as a novel approach for the treatment of pain and inflammation.
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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 |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BockMark GMG,
pubmed-author:ChangRonald KRK,
pubmed-author:CookJacquelynnJ,
pubmed-author:Di MarcoChristina NCN,
pubmed-author:DiPardoRobert MRM,
pubmed-author:HarrellC MeachamCM,
pubmed-author:HessJ FredJF,
pubmed-author:HolahanMarie AMA,
pubmed-author:KimJune JJJ,
pubmed-author:KudukScott DSD,
pubmed-author:MurphyKathy LKL,
pubmed-author:PettiboneDouglas JDJ,
pubmed-author:PrueksaritanontThomayantT,
pubmed-author:RansomRichard WRW,
pubmed-author:ReissDuane RDR,
pubmed-author:SainNovaN,
pubmed-author:SchirripaKathy MKM,
pubmed-author:TangCuyueC,
pubmed-author:UrbanMark OMO,
pubmed-author:WaiJenny M CJM,
pubmed-author:WoodMichael RMR
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
272-82
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pubmed:meshHeading |
pubmed-meshheading:17228869-Acetamides,
pubmed-meshheading:17228869-Administration, Oral,
pubmed-meshheading:17228869-Amides,
pubmed-meshheading:17228869-Aminobiphenyl Compounds,
pubmed-meshheading:17228869-Analgesics,
pubmed-meshheading:17228869-Animals,
pubmed-meshheading:17228869-Animals, Genetically Modified,
pubmed-meshheading:17228869-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:17228869-Benzoates,
pubmed-meshheading:17228869-Biological Availability,
pubmed-meshheading:17228869-Blood-Brain Barrier,
pubmed-meshheading:17228869-Brain,
pubmed-meshheading:17228869-CHO Cells,
pubmed-meshheading:17228869-Cercopithecus aethiops,
pubmed-meshheading:17228869-Cricetinae,
pubmed-meshheading:17228869-Cricetulus,
pubmed-meshheading:17228869-Cyclopropanes,
pubmed-meshheading:17228869-Female,
pubmed-meshheading:17228869-Humans,
pubmed-meshheading:17228869-Macaca mulatta,
pubmed-meshheading:17228869-Male,
pubmed-meshheading:17228869-Mice,
pubmed-meshheading:17228869-Rabbits,
pubmed-meshheading:17228869-Radioligand Assay,
pubmed-meshheading:17228869-Rats,
pubmed-meshheading:17228869-Receptor, Bradykinin B1,
pubmed-meshheading:17228869-Species Specificity,
pubmed-meshheading:17228869-Spinal Cord,
pubmed-meshheading:17228869-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Development of orally bioavailable and CNS penetrant biphenylaminocyclopropane carboxamide bradykinin B1 receptor antagonists.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, P.O. Box 4, West Point, Pennsylvania 19486, USA.
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pubmed:publicationType |
Journal Article
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