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rdf:type |
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lifeskim:mentions |
umls-concept:C0031327,
umls-concept:C0038477,
umls-concept:C0056154,
umls-concept:C0205177,
umls-concept:C0205531,
umls-concept:C0220781,
umls-concept:C0220825,
umls-concept:C0226896,
umls-concept:C0243071,
umls-concept:C0441655,
umls-concept:C0442027,
umls-concept:C1515655,
umls-concept:C1527415,
umls-concept:C1883254
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pubmed:issue |
8
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pubmed:dateCreated |
2002-4-4
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pubmed:abstractText |
The synthesis and structure-activity relationship study of a series of compounds with heterocycles in place of the cis double bond in combretastatin A-4 (CA-4) are described. Substituted tosylmethyl isocyanides were found to be the key intermediates in construction of the heterocycles. Cytotoxicities of the heterocycle-based CA-4 analogues were evaluated against NCI-H460 and HCT-15 cancer cell lines. 3-Amino-4-methoxyphenyl and N-methyl-indol-5-yl were the best replacements for the 3-hydroxy-4-methoxyphenyl in CA-4. 4,5-Disubstituted imidazole was found to be the best for the replacement of the cis double bond in CA-4. Medicinal chemistry efforts led to the discovery of compounds 24h and 25f that were found to be 32 and 82% bioavailable, respectively, in rat. Evaluation of 24h and 25f against murine M5076 reticulum sarcoma in mice revealed that both compounds were orally efficacious with an increase in life span of 38.5 and 40.5%, respectively.
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pubmed:commentsCorrections |
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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 |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BarrKenneth JKJ,
pubmed-author:CredoR BruceRB,
pubmed-author:FrostDavidD,
pubmed-author:GherkeLauraL,
pubmed-author:HannickSteven MSM,
pubmed-author:HuiYu-HuaYH,
pubmed-author:LeeJang YJY,
pubmed-author:LiQunQ,
pubmed-author:MarshKennanK,
pubmed-author:McCroskeyRichard WRW,
pubmed-author:RosenbergSaul HSH,
pubmed-author:ShamHing LHL,
pubmed-author:WangLeL,
pubmed-author:WarnerRobertR,
pubmed-author:WoodsKeith WKW,
pubmed-author:Zielinski-MozngNicoletteN
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
45
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1697-711
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11931625-Administration, Oral,
pubmed-meshheading:11931625-Animals,
pubmed-meshheading:11931625-Antineoplastic Agents,
pubmed-meshheading:11931625-Biopolymers,
pubmed-meshheading:11931625-Cell Division,
pubmed-meshheading:11931625-Dogs,
pubmed-meshheading:11931625-Drug Screening Assays, Antitumor,
pubmed-meshheading:11931625-Haplorhini,
pubmed-meshheading:11931625-Humans,
pubmed-meshheading:11931625-Imidazoles,
pubmed-meshheading:11931625-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:11931625-Mice,
pubmed-meshheading:11931625-Mice, Nude,
pubmed-meshheading:11931625-Neoplasm Transplantation,
pubmed-meshheading:11931625-Rats,
pubmed-meshheading:11931625-Stilbenes,
pubmed-meshheading:11931625-Structure-Activity Relationship,
pubmed-meshheading:11931625-Transplantation, Heterologous,
pubmed-meshheading:11931625-Tubulin,
pubmed-meshheading:11931625-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation.
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pubmed:affiliation |
Global Pharmaceutical R & D, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6101, USA. le.wang@abbott.com
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pubmed:publicationType |
Journal Article
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