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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2011-2-7
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pubmed:abstractText |
Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.
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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 |
Feb
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:BensonG MGM,
pubmed-author:BleicherK HKH,
pubmed-author:BlumDD,
pubmed-author:ChaputEE,
pubmed-author:ClemannNN,
pubmed-author:FengSS,
pubmed-author:GardelJJ,
pubmed-author:GretherUU,
pubmed-author:HartmanPP,
pubmed-author:KuhnBB,
pubmed-author:MartinR ERE,
pubmed-author:PlancherJ-MJM,
pubmed-author:RichterHans G FHG,
pubmed-author:RudolphM GMG,
pubmed-author:SchulerFF,
pubmed-author:TaylorSS
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1134-40
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pubmed:meshHeading |
pubmed-meshheading:21269824-4-Aminobenzoic Acid,
pubmed-meshheading:21269824-Administration, Oral,
pubmed-meshheading:21269824-Animals,
pubmed-meshheading:21269824-Benzimidazoles,
pubmed-meshheading:21269824-Binding Sites,
pubmed-meshheading:21269824-Computer Simulation,
pubmed-meshheading:21269824-Crystallography, X-Ray,
pubmed-meshheading:21269824-Humans,
pubmed-meshheading:21269824-Male,
pubmed-meshheading:21269824-Mice,
pubmed-meshheading:21269824-Mice, Inbred C57BL,
pubmed-meshheading:21269824-Microsomes, Liver,
pubmed-meshheading:21269824-Molecular Conformation,
pubmed-meshheading:21269824-Rats,
pubmed-meshheading:21269824-Rats, Wistar,
pubmed-meshheading:21269824-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:21269824-Receptors, LDL,
pubmed-meshheading:21269824-Structure-Activity Relationship
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pubmed:year |
2011
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pubmed:articleTitle |
Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties.
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pubmed:affiliation |
F. Hoffmann-La Roche Ltd, Pharmaceutical Research, Grenzacherstrasse, CH-4070 Basel, Switzerland. hans.richter@roche.com
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pubmed:publicationType |
Journal Article
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