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rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0053225,
umls-concept:C0205250,
umls-concept:C0205531,
umls-concept:C0226896,
umls-concept:C0231491,
umls-concept:C0442027,
umls-concept:C0470187,
umls-concept:C0700307,
umls-concept:C1332700,
umls-concept:C1512523,
umls-concept:C1527415,
umls-concept:C1611588,
umls-concept:C1880355
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|
pubmed:issue |
13
|
|
pubmed:dateCreated |
2011-6-24
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|
pubmed:abstractText |
Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented.
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pubmed:language |
eng
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|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
1464-3391
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|
pubmed:author |
pubmed-author:FukushimaDaikichiD,
pubmed-author:HisaichiKatsuyaK,
pubmed-author:MaedaKenjiK,
pubmed-author:MinamotoChiakiC,
pubmed-author:MitsuyaHiroakiH,
pubmed-author:MurotaMasayukiM,
pubmed-author:NakaiHisaoH,
pubmed-author:NishiyamaToshihikoT,
pubmed-author:NishizawaRenaR,
pubmed-author:SagawaKenjiK,
pubmed-author:ShibayamaShiroS,
pubmed-author:TadaHideakiH,
pubmed-author:TakaokaYoshikazuY
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
19
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
4028-42
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|
pubmed:meshHeading |
pubmed-meshheading:21658961-Administration, Oral,
pubmed-meshheading:21658961-Animals,
pubmed-meshheading:21658961-Anti-HIV Agents,
pubmed-meshheading:21658961-Benzoic Acids,
pubmed-meshheading:21658961-Diketopiperazines,
pubmed-meshheading:21658961-Dogs,
pubmed-meshheading:21658961-Drug Evaluation, Preclinical,
pubmed-meshheading:21658961-Guinea Pigs,
pubmed-meshheading:21658961-Haplorhini,
pubmed-meshheading:21658961-Humans,
pubmed-meshheading:21658961-Rabbits,
pubmed-meshheading:21658961-Rats,
pubmed-meshheading:21658961-Receptors, CCR5,
pubmed-meshheading:21658961-Structure-Activity Relationship
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|
pubmed:year |
2011
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|
pubmed:articleTitle |
Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: a highly potent orally available CCR5 selective antagonist.
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|
pubmed:affiliation |
Medicinal Chemistry Research Laboratory, Ono Pharmaceutical Co. Ltd, Shimamoto, Mishima, Osaka, Japan. r.nishizawa@ono.co.jp
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pubmed:publicationType |
Journal Article
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