pubmed-article:20043700 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0014442 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0220908 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C1364818 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0206755 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C1527148 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0205234 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0024485 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0598139 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0185125 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0181586 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C1533134 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
pubmed-article:20043700 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
pubmed-article:20043700 | pubmed:issue | 3 | lld:pubmed |
pubmed-article:20043700 | pubmed:dateCreated | 2010-2-4 | lld:pubmed |
pubmed-article:20043700 | pubmed:abstractText | Fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design were used to identify novel inhibitors for BACE-1. A rapid optimization of an initial NMR hit was achieved by a combination of NMR and a functional assay, resulting in the identification of an isothiourea hit with a K(d) of 15 microM for BACE-1. NMR data and the crystal structure revealed that this hit makes H-bond interactions with the two catalytic aspartates, occupies the nonprime side region of the active site of BACE-1, and extends toward the S3 subpocket (S3sp). A focused NMR-based search for heterocyclic isothiourea isosteres resulted in several distinct classes of BACE-1 active site directed compounds with improved chemical stability and physicochemical properties. The strategy for optimization of the 2-aminopyridine lead series to potent inhibitors of BACE-1 was demonstrated. The structure-based design of a cyclic acylguanidine lead series and its optimization into nanomolar BACE-1 inhibitors are the subject of the companion paper | lld:pubmed |
pubmed-article:20043700 | pubmed:language | eng | lld:pubmed |
pubmed-article:20043700 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20043700 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:20043700 | pubmed:month | Feb | lld:pubmed |
pubmed-article:20043700 | pubmed:issn | 1520-4804 | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:HunterJohn... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:ParkerEric... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:VoigtJohannes... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:WyssDaniel... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:McKittrickBri... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:SmithElizabet... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:WangYu-SenYS | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:GreenleeWilli... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:SeniorMary... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:MadisonVincen... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:StamfordAndre... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:KennedyMatthe... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:StricklandCor... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:BeyerBrian... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:CzarnieckiMic... | lld:pubmed |
pubmed-article:20043700 | pubmed:author | pubmed-author:NechutaTerry... | lld:pubmed |
pubmed-article:20043700 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:20043700 | pubmed:day | 11 | lld:pubmed |
pubmed-article:20043700 | pubmed:volume | 53 | lld:pubmed |
pubmed-article:20043700 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:20043700 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:20043700 | pubmed:pagination | 942-50 | lld:pubmed |
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pubmed-article:20043700 | pubmed:year | 2010 | lld:pubmed |
pubmed-article:20043700 | pubmed:articleTitle | Application of fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design to identify novel microM leads for the development of nM BACE-1 (beta-site APP cleaving enzyme 1) inhibitors. | lld:pubmed |
pubmed-article:20043700 | pubmed:affiliation | Schering-Plough Research Institute, 320 Bent Street, Cambridge, Massachusetts 02141, USA. allen.yu-sen.wang@spcorp.com | lld:pubmed |
pubmed-article:20043700 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:20043700 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
pubmed-article:20043700 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:20043700 | lld:chembl |