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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2007-7-10
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pubmed:abstractText |
Utilization of N-substituted-4-hydroxy-3-methylsulfonanilidoethanolamines 1 as selective beta(3) agonists is complicated by their propensity to undergo metabolic oxidative N-dealkylation, generating 0.01-2% of a very potent alpha(1) adrenergic agonist 2. A summary of the SAR for this hepatic microsomal conversion precedes presentation of strategies to maintain the advantages of chemotype 1 while mitigating the consequences of N-dealkylation. This effort led to the identification of 4-hydroxy-3-methylsulfonanilidopropanolamines 15 for which the SAR for the unique stereochemical requirements for binding to the beta adrenergic receptors culminated in the identification of the potent, selective beta(3) agonist 15f.
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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 |
Aug
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:Abboa-OffeiB EBE,
pubmed-author:AhmedSS,
pubmed-author:AllenG TGT,
pubmed-author:CaringalYY,
pubmed-author:CatII,
pubmed-author:ChengP T WPT,
pubmed-author:DejnekaTT,
pubmed-author:DickinsonK EKE,
pubmed-author:FrohlichB HBH,
pubmed-author:GavamMM,
pubmed-author:GeorgeR JRJ,
pubmed-author:GirotraRR,
pubmed-author:GodfreyJ DJD,
pubmed-author:HangelandJJ,
pubmed-author:HarperT WTW,
pubmed-author:McCannPP,
pubmed-author:MikkilineniAA,
pubmed-author:RussellA DAD,
pubmed-author:SeymourA AAA,
pubmed-author:ShawKK,
pubmed-author:SherP MPM,
pubmed-author:SkwishSS,
pubmed-author:SlusarchykD ADA,
pubmed-author:TesfamariamBB,
pubmed-author:WaldronT LTL,
pubmed-author:WashburnW NWN,
pubmed-author:WuGG,
pubmed-author:ZhangHH,
pubmed-author:ZhangMM
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4290-6
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
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pubmed:year |
2007
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pubmed:articleTitle |
Arylpropanolamines: selective beta3 agonists arising from strategies to mitigate phase I metabolic transformations.
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pubmed:affiliation |
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. William.Washburn@bms.com
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pubmed:publicationType |
Journal Article
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