| pubmed-article:11741489 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C0013030 | lld:lifeskim |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C0038477 | lld:lifeskim |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C0243076 | lld:lifeskim |
| pubmed-article:11741489 | lifeskim:mentions | umls-concept:C0045887 | lld:lifeskim |
| pubmed-article:11741489 | pubmed:issue | 26 | lld:pubmed |
| pubmed-article:11741489 | pubmed:dateCreated | 2001-12-19 | lld:pubmed |
| pubmed-article:11741489 | pubmed:abstractText | 5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D(3) receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D(3) antagonists. Thus, combinations of various alkyl groups were generally inactive at the D(3) receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D(3) binding affinity, the D(2) affinity is also enhanced, resulting in a less than 4-fold preference for the D(3) receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D(3) antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH(3).Me(2)S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et(3)SiH to give the desired product 3 in good overall yield of ( approximately 65%) from the indanone 5c. | lld:pubmed |
| pubmed-article:11741489 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11741489 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11741489 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11741489 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11741489 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:11741489 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:CarlssonAA | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:SmithM WMW | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:LinC HCH | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:DinhD MDM | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:HaberC LCL | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:LOWEC HCHJr | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:ZayaM JMJ | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:DuncanJ NJN | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:NicholsN FNF | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:LajinessM EME | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:Haadsma-Svens... | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:SvenssonK AKA | lld:pubmed |
| pubmed-article:11741489 | pubmed:author | pubmed-author:CleekK AKA | lld:pubmed |
| pubmed-article:11741489 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11741489 | pubmed:day | 20 | lld:pubmed |
| pubmed-article:11741489 | pubmed:volume | 44 | lld:pubmed |
| pubmed-article:11741489 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11741489 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11741489 | pubmed:pagination | 4716-32 | lld:pubmed |
| pubmed-article:11741489 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:11741489 | pubmed:meshHeading | pubmed-meshheading:11741489... | lld:pubmed |
| pubmed-article:11741489 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11741489 | pubmed:articleTitle | Dopamine D(3) receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans. | lld:pubmed |
| pubmed-article:11741489 | pubmed:affiliation | Structural, Analytical and Medicinal Chemistry, Pharmacia, 7255-209-129.2, 301 Henrietta Street, Kalamazoo, Michigan 49007-4940, USA. sue.haadsma-svensson@pharmacia.com | lld:pubmed |
| pubmed-article:11741489 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11741489 | pubmed:publicationType | In Vitro | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:11741489 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:11741489 | lld:pubmed |
