| pubmed-article:2296019 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0007610 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0034325 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0360714 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0392747 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0599474 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0678594 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C1554963 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0205549 | lld:lifeskim |
| pubmed-article:2296019 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:2296019 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:2296019 | pubmed:dateCreated | 1990-2-22 | lld:pubmed |
| pubmed-article:2296019 | pubmed:abstractText | A novel series of trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones and their dihydroxy acid derivatives were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. A systematic study of substitution at the 2- and 5-positions of the pyrrole ring revealed that optimum potency was realized with the 2-(4-fluorophenyl)-5-isopropyl derivative 8x, which possessed 30% of the in vitro activity of the potent fungal metabolite compactin (I). A molecular modeling analysis led to the description of a pharmacophore model characterized by (A) length limits of 5.9 and 3.3 A for the 2- and 5-substituents, respectively, as well as an overall width limit of 10.6 A across the pyrrole ring from the 2- to the 5-substituent and (B) an orientation of the ethyl(ene) bridge to the 4-hydroxypyran-2-one ring nearly perpendicular to the planes of the parent pyrrole, hexahydronaphthalene, and phenyl rings of the structures examined (Figure 3, theta = 80-110 degrees). Attempts to more closely mimic compactin's polar isobutyric ester side chain with the synthesis of 2-phenylpyrroles containing polar phenyl substituents resulted in analogues with equal or slightly reduced potencies when compared to the 2-[(unsubstituted or 4-fluoro)phenyl]pyrroles, supporting the hypothesis that inhibitory potency is relatively insensitive to side-chain polarity or charge distribution in this area. | lld:pubmed |
| pubmed-article:2296019 | pubmed:language | eng | lld:pubmed |
| pubmed-article:2296019 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2296019 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:2296019 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:2296019 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:NewtonR SRS | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:HoefleM LML | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:StrattonC DCD | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:WilsonM WMW | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:OrtwineD FDF | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:RothB DBD | lld:pubmed |
| pubmed-article:2296019 | pubmed:author | pubmed-author:SliskovicD... | lld:pubmed |
| pubmed-article:2296019 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:2296019 | pubmed:volume | 33 | lld:pubmed |
| pubmed-article:2296019 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:2296019 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:2296019 | pubmed:pagination | 21-31 | lld:pubmed |
| pubmed-article:2296019 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
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| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
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| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:meshHeading | pubmed-meshheading:2296019-... | lld:pubmed |
| pubmed-article:2296019 | pubmed:year | 1990 | lld:pubmed |
| pubmed-article:2296019 | pubmed:articleTitle | Inhibitors of cholesterol biosynthesis. 1. trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a novel series of HMG-CoA reductase inhibitors. 1. Effects of structural modifications at the 2- and 5-positions of the pyrrole nucleus. | lld:pubmed |
| pubmed-article:2296019 | pubmed:affiliation | Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105. | lld:pubmed |
| pubmed-article:2296019 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:2296019 | pubmed:publicationType | Comparative Study | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:2296019 | lld:chembl |
