| pubmed-article:10447953 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0033262 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0220825 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0449445 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0439611 | lld:lifeskim |
| pubmed-article:10447953 | lifeskim:mentions | umls-concept:C0597565 | lld:lifeskim |
| pubmed-article:10447953 | pubmed:issue | 16 | lld:pubmed |
| pubmed-article:10447953 | pubmed:dateCreated | 1999-9-2 | lld:pubmed |
| pubmed-article:10447953 | pubmed:abstractText | The synthesis and preliminary evaluation of a novel prodrug approach for improving the water solubility of drugs containing a tertiary amine group are reported. The prodrug synthesis involves a nucleophilic substitution reaction between the parent tertiary amine and a novel derivatizing reagent, di-tert-butyl chloromethyl phosphate, resulting in formation of the quaternary salt. The tertiary butyl groups are easily removed under acidic conditions with trifluoroacetic acid giving the N-phosphonooxymethyl prodrug in the free phosphoric acid form, which can subsequently be converted to the desired salt form. The synthesis was successfully applied to a model compound (quinuclidine) and to three tertiary amine-containing drugs (cinnarizine, loxapine, and amiodarone). The prodrugs were designed to undergo a two-step bioreversion process. The first step was an enzyme-catalyzed rate-determining dephosphorylation followed by spontaneous chemical breakdown of the N-hydroxymethyl intermediate to give the parent drug. Selected prodrugs were shown to be substrates for alkaline phosphatase in vitro. A preliminary in vivo study confirmed the ability of the cinnarizine prodrug to be rapidly and completely converted to cinnarizine in a beagle dog following iv administration. | lld:pubmed |
| pubmed-article:10447953 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10447953 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10447953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10447953 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10447953 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:10447953 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:10447953 | pubmed:author | pubmed-author:StellaV JVJ | lld:pubmed |
| pubmed-article:10447953 | pubmed:author | pubmed-author:ZygmuntJJ | lld:pubmed |
| pubmed-article:10447953 | pubmed:author | pubmed-author:GeorgG IGI | lld:pubmed |
| pubmed-article:10447953 | pubmed:author | pubmed-author:KriseJ PJP | lld:pubmed |
| pubmed-article:10447953 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10447953 | pubmed:day | 12 | lld:pubmed |
| pubmed-article:10447953 | pubmed:volume | 42 | lld:pubmed |
| pubmed-article:10447953 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10447953 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10447953 | pubmed:pagination | 3094-100 | lld:pubmed |
| pubmed-article:10447953 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:10447953 | pubmed:meshHeading | pubmed-meshheading:10447953... | lld:pubmed |
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| pubmed-article:10447953 | pubmed:meshHeading | pubmed-meshheading:10447953... | lld:pubmed |
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| pubmed-article:10447953 | pubmed:meshHeading | pubmed-meshheading:10447953... | lld:pubmed |
| pubmed-article:10447953 | pubmed:meshHeading | pubmed-meshheading:10447953... | lld:pubmed |
| pubmed-article:10447953 | pubmed:meshHeading | pubmed-meshheading:10447953... | lld:pubmed |
| pubmed-article:10447953 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10447953 | pubmed:articleTitle | Novel prodrug approach for tertiary amines: synthesis and preliminary evaluation of N-phosphonooxymethyl prodrugs. | lld:pubmed |
| pubmed-article:10447953 | pubmed:affiliation | Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, Kansas 66047, USA. | lld:pubmed |
| pubmed-article:10447953 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10447953 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:10447953 | lld:chembl |
