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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-12-26
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pubmed:abstractText |
Rational modification of a previously identified spirohydantoin lead structure has identified a series of potent spiroazaoxindole CGRP receptor antagonists. The azaoxindole was found to be a general replacement for the hydantoin that consistently improved in vitro potency. The combination of the indanylspiroazaoxindole and optimized benzimidazolinones led to highly potent antagonists (e.g., 25, CGRP K(i)=40pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus.
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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 |
1464-3405
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pubmed:author |
pubmed-author:BednarRodney ARA,
pubmed-author:BellIan MIM,
pubmed-author:Blair ZartmanCC,
pubmed-author:BrunoJoseph GJG,
pubmed-author:FayJohn FJF,
pubmed-author:GallicchioSteven NSN,
pubmed-author:GrahamSamuel LSL,
pubmed-author:JohnstonVictor KVK,
pubmed-author:KaneStefanie ASA,
pubmed-author:MooreEric LEL,
pubmed-author:MosserScott DSD,
pubmed-author:QuigleyAmy GAG,
pubmed-author:SalvatoreChristopher ACA,
pubmed-author:StumpCraig ACA,
pubmed-author:ThebergeCory RCR,
pubmed-author:VaccaJoseph PJP,
pubmed-author:WilliamsTheresa MTM,
pubmed-author:ZhangXu-FangXF
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
214-7
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pubmed:meshHeading |
pubmed-meshheading:19010673-Administration, Oral,
pubmed-meshheading:19010673-Animals,
pubmed-meshheading:19010673-Biological Availability,
pubmed-meshheading:19010673-Dogs,
pubmed-meshheading:19010673-Drug Discovery,
pubmed-meshheading:19010673-Humans,
pubmed-meshheading:19010673-Indoles,
pubmed-meshheading:19010673-Macaca mulatta,
pubmed-meshheading:19010673-Receptors, Calcitonin Gene-Related Peptide,
pubmed-meshheading:19010673-Spiro Compounds,
pubmed-meshheading:19010673-Structure-Activity Relationship
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pubmed:year |
2009
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pubmed:articleTitle |
The discovery of highly potent CGRP receptor antagonists.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck & Co, Inc, West Point, PA 19486, USA. craig_stump@merck.com
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pubmed:publicationType |
Journal Article
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