| pubmed-article:19492813 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19492813 | lifeskim:mentions | umls-concept:C0030520 | lld:lifeskim |
| pubmed-article:19492813 | lifeskim:mentions | umls-concept:C0249742 | lld:lifeskim |
| pubmed-article:19492813 | lifeskim:mentions | umls-concept:C0243076 | lld:lifeskim |
| pubmed-article:19492813 | pubmed:issue | 13 | lld:pubmed |
| pubmed-article:19492813 | pubmed:dateCreated | 2009-7-2 | lld:pubmed |
| pubmed-article:19492813 | pubmed:abstractText | Functional screening of the former SmithKline Beecham compound collection against the human calcium receptor (CaR) resulted in the identification of the amino alcohol-based hit 2 (IC(50) = 11 microM). Structure-activity studies of 2 focused on the optimization of the right- and left-hand side aromatic moieties as well as the amino alcohol linker region. Critical to the optimization of this antagonist template was the discovery that the chirality of the C-2 secondary alcohol played a key role in enhancing both CaR potency as well as selectivity over the beta-adrenergic receptor subtypes. These SAR studies ultimately led to the identification of 38 (NPS 2143; SB-262470A), a potent and orally active CaR antagonist. Pharmacokinetic characterization of 38 in the rat revealed that this molecule had a large volume of distribution (11 L/kg), which resulted in a prolonged systemic exposure, protracted increases in the plasma levels of PTH, and an overall lack of net bone formation effect in a rodent model of osteoporosis. | lld:pubmed |
| pubmed-article:19492813 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19492813 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19492813 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19492813 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19492813 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19492813 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19492813 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19492813 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:19492813 | pubmed:issn | 1520-4804 | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:LeeJohnJ | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:YangZhengZ | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:SmithBrian... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:CallahanJames... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:FoxJohnJ | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:WardKeith WKW | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:GowenMaxineM | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:NemethEdward... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:KeenanRichard... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:Van... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:MarquisRobert... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:RoethkeTheres... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:TroutRobert... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:LoganSarahS | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:LagoAmparo... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:DelMarEric... | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:ShimizuScottS | lld:pubmed |
| pubmed-article:19492813 | pubmed:author | pubmed-author:BhatnagarPrad... | lld:pubmed |
| pubmed-article:19492813 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19492813 | pubmed:day | 9 | lld:pubmed |
| pubmed-article:19492813 | pubmed:volume | 52 | lld:pubmed |
| pubmed-article:19492813 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19492813 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19492813 | pubmed:pagination | 3982-93 | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:meshHeading | pubmed-meshheading:19492813... | lld:pubmed |
| pubmed-article:19492813 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19492813 | pubmed:articleTitle | Antagonists of the calcium receptor I. Amino alcohol-based parathyroid hormone secretagogues. | lld:pubmed |
| pubmed-article:19492813 | pubmed:affiliation | Department of Medicinal Chemistry, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA. Robert.W.Marquis@gsk.com | lld:pubmed |
| pubmed-article:19492813 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:19492813 | lld:chembl |
