| pubmed-article:18363376 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18363376 | lifeskim:mentions | umls-concept:C0001041 | lld:lifeskim |
| pubmed-article:18363376 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:18363376 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:18363376 | lifeskim:mentions | umls-concept:C0456387 | lld:lifeskim |
| pubmed-article:18363376 | lifeskim:mentions | umls-concept:C0028822 | lld:lifeskim |
| pubmed-article:18363376 | lifeskim:mentions | umls-concept:C0068935 | lld:lifeskim |
| pubmed-article:18363376 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:18363376 | pubmed:dateCreated | 2008-4-25 | lld:pubmed |
| pubmed-article:18363376 | pubmed:abstractText | In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series. | lld:pubmed |
| pubmed-article:18363376 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18363376 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18363376 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18363376 | pubmed:month | May | lld:pubmed |
| pubmed-article:18363376 | pubmed:issn | 0022-3263 | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:CrooksPeter... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:DayCynthia... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:BhattiBalwind... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:BreiningScott... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:CaldwellWilli... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:DeoNiranjanN | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:MillerCraig... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:StrachanJon-P... | lld:pubmed |
| pubmed-article:18363376 | pubmed:author | pubmed-author:TahiriPersida... | lld:pubmed |
| pubmed-article:18363376 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18363376 | pubmed:day | 2 | lld:pubmed |
| pubmed-article:18363376 | pubmed:volume | 73 | lld:pubmed |
| pubmed-article:18363376 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18363376 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18363376 | pubmed:pagination | 3497-507 | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:meshHeading | pubmed-meshheading:18363376... | lld:pubmed |
| pubmed-article:18363376 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18363376 | pubmed:articleTitle | Synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a class of potent nicotinic acetylcholine receptor-ligands. | lld:pubmed |
| pubmed-article:18363376 | pubmed:affiliation | Targacept, Inc., 200 East 1st Street, Suite 300, Winston-Salem, North Carolina 27101-4165, USA. bhattib@targacept.com | lld:pubmed |
| pubmed-article:18363376 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18363376 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18363376 | lld:pubmed |
