| pubmed-article:17935989 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0031327 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0041942 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0184511 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C1332753 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0038477 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C2003903 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:17935989 | lifeskim:mentions | umls-concept:C0439611 | lld:lifeskim |
| pubmed-article:17935989 | pubmed:issue | 23 | lld:pubmed |
| pubmed-article:17935989 | pubmed:dateCreated | 2007-11-6 | lld:pubmed |
| pubmed-article:17935989 | pubmed:abstractText | A new series of potent macrocyclic urea-based Chk1 inhibitors are described. A detailed SAR study on the 4-position of the phenyl ring of the 14-member macrocyclic ureas 1a and d led to the identification of the potent Chk1 inhibitors 2, 5-7, 10, 13, 14, 19-21, 25, 27, and 31-34. These compounds significantly sensitize tumor cells to the DNA-damaging antitumor agent doxorubicin in a cell-based assay and efficiently abrogate the doxorubicin-induced G2/M and camptothecin-induced S checkpoints, indicating that the potent biological activities of these compounds are mechanism-based through Chk1 inhibition. Kinome profiling analysis of a representative macrocyclic urea 25 against a panel of 120 kinases indicates that these novel macrocyclic ureas are highly selective Chk1 inhibitors. Preliminary PK studies of 1a and b suggest that the 14-member macrocyclic inhibitors may possess better PK properties than their 15-member counterparts. An improved synthesis of 2 and 20 by using 2-(trimethylsilyl)ethoxycarbonyl (Teoc) to protect the amino group not only readily provided the desired compounds in pure form but also facilitated the scale up of potent compounds for various biological studies. | lld:pubmed |
| pubmed-article:17935989 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17935989 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17935989 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17935989 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17935989 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17935989 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17935989 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17935989 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17935989 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17935989 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:17935989 | pubmed:issn | 1464-3405 | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:KovarPeterP | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:RosenbergSaul... | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:TaoZhi-FuZF | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:JohnsonEricE | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:LinNan-HorngN... | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:SowinThomasT | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:BuiMai-HaMH | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:ZhangHaiyingH | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:ChenZehanZ | lld:pubmed |
| pubmed-article:17935989 | pubmed:author | pubmed-author:BouskaJennife... | lld:pubmed |
| pubmed-article:17935989 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:17935989 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:17935989 | pubmed:volume | 17 | lld:pubmed |
| pubmed-article:17935989 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17935989 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17935989 | pubmed:pagination | 6593-601 | lld:pubmed |
| pubmed-article:17935989 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:meshHeading | pubmed-meshheading:17935989... | lld:pubmed |
| pubmed-article:17935989 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17935989 | pubmed:articleTitle | Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and preliminary pharmacokinetics. | lld:pubmed |
| pubmed-article:17935989 | pubmed:affiliation | Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Zhi-Fu.Tao@abbott.com | lld:pubmed |
| pubmed-article:17935989 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17935989 | pubmed:publicationType | Comparative Study | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:17935989 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:17935989 | lld:pubmed |
