| pubmed-article:17205182 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17205182 | lifeskim:mentions | umls-concept:C0042153 | lld:lifeskim |
| pubmed-article:17205182 | lifeskim:mentions | umls-concept:C0002508 | lld:lifeskim |
| pubmed-article:17205182 | lifeskim:mentions | umls-concept:C1333707 | lld:lifeskim |
| pubmed-article:17205182 | lifeskim:mentions | umls-concept:C1510827 | lld:lifeskim |
| pubmed-article:17205182 | lifeskim:mentions | umls-concept:C1521827 | lld:lifeskim |
| pubmed-article:17205182 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:17205182 | pubmed:dateCreated | 2007-1-5 | lld:pubmed |
| pubmed-article:17205182 | pubmed:abstractText | A family of previously reported ring-closing metathesis (RCM)-derived macrocycles that exhibit potent Grb2 SH2 domain-binding affinity is characterized by stereoselectively-introduced upper ring junctions that bear bicyclic aryl substituents. However, the synthetic complexity of these macrocycles presents a potential limit to their therapeutic application. Therefore, the current study was undertaken to simplify these macrocycles through the use of achiral 4-pentenylamides as ring-forming components. A series of macrocycles (5a-f) was prepared bearing both open and cyclic constructs at the upper ring junction. The Grb2 SH2 domain-binding affinities of these macrocycles varied, with higher affinities being obtained with cyclo-substituents. The most potent analogue (5d) contained a cyclohexyl group and exhibited Grb2 SH2 domain-binding affinity (K(D) = 1.3 nM) that was nearly equal to the parent macrocycle (2), which bore a stereoselectively-introduced naphthylmethyl substituent at the upper ring junction (K(D) = 0.9 nM). The results of this study advance design considerations that should facilitate the development of Grb2 SH2 domain-binding antagonists. | lld:pubmed |
| pubmed-article:17205182 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17205182 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17205182 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17205182 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17205182 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:17205182 | pubmed:issn | 1477-0520 | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:JinLL | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:BurkeTerrence... | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:FisherRobert... | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:BottaroDonald... | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:WorthyKaren... | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:GiubellinoAle... | lld:pubmed |
| pubmed-article:17205182 | pubmed:author | pubmed-author:BinduLakshman... | lld:pubmed |
| pubmed-article:17205182 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17205182 | pubmed:day | 21 | lld:pubmed |
| pubmed-article:17205182 | pubmed:volume | 5 | lld:pubmed |
| pubmed-article:17205182 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17205182 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17205182 | pubmed:pagination | 367-72 | lld:pubmed |
| pubmed-article:17205182 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:meshHeading | pubmed-meshheading:17205182... | lld:pubmed |
| pubmed-article:17205182 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17205182 | pubmed:articleTitle | Utilization of achiral alkenyl amines for the preparation of high affinity Grb2 SH2 domain-binding macrocycles by ring-closing metathesis. | lld:pubmed |
| pubmed-article:17205182 | pubmed:affiliation | Laboratory of Medicinal Chemistry, Bldg. 376 Boyles St., Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, MD 21702, USA. | lld:pubmed |
| pubmed-article:17205182 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17205182 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| pubmed-article:17205182 | pubmed:publicationType | Research Support, N.I.H., Intramural | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:17205182 | lld:pubmed |
