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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
13
|
| pubmed:dateCreated |
1998-7-9
|
| pubmed:abstractText |
Benzylimidazolines may represent a class of 5-HT1D ligands that has yet to be exploited. On the basis of a previous report that the 2-(substituted-benzyl)imidazoline alpha-adrenergic agonist oxymetazoline (8) binds with high affinity at calf brain 5-HT1D receptors, we explored the structure-affinity relationships of a series of related derivatives. Each of the aromatic substituents was removed and then reinstated in a systematic manner to determine the influence of the individual substituents on binding. It was found that all of the aromatic substituents of 8 act in concert to impart high affinity. However, although the 3-hydroxy group could be removed without significantly reducing affinity for h5-HT1D (i.e., human 5-HT1Dalpha) receptors, this modification reduced h5-HT1B (i.e., human 5-HT1Dbeta) receptor affinity by nearly 50-fold. The 2, 6-dimethyl groups also contribute to binding but seem to play a greater role for h5-HT1B binding than h5-HT1D binding. With the appropriate structural modifications, several compounds were identified that display 20- to >100-fold selectivity for h5-HT1D versus h5-HT1B receptors. Preliminary functional data suggest that these compounds behave as agonists. Given that 5-HT1D agonists are currently being explored for their antimigraine action and that activation of h5-HT1B receptors might be associated with cardiovascular side effects, h5-HT1D-selective agents may offer a new lead for the development of therapeutically efficacious agents.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/HTR1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Oxymetazoline,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1D,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
18
|
| pubmed:volume |
41
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2243-51
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:9632357-Adrenergic alpha-Agonists,
pubmed-meshheading:9632357-Animals,
pubmed-meshheading:9632357-CHO Cells,
pubmed-meshheading:9632357-Cricetinae,
pubmed-meshheading:9632357-Cyclic AMP,
pubmed-meshheading:9632357-Humans,
pubmed-meshheading:9632357-Isometric Contraction,
pubmed-meshheading:9632357-Ligands,
pubmed-meshheading:9632357-Male,
pubmed-meshheading:9632357-Muscle, Smooth, Vascular,
pubmed-meshheading:9632357-Oxymetazoline,
pubmed-meshheading:9632357-Rabbits,
pubmed-meshheading:9632357-Receptor, Serotonin, 5-HT1B,
pubmed-meshheading:9632357-Receptor, Serotonin, 5-HT1D,
pubmed-meshheading:9632357-Receptors, Adrenergic, alpha,
pubmed-meshheading:9632357-Receptors, Serotonin,
pubmed-meshheading:9632357-Saphenous Vein,
pubmed-meshheading:9632357-Serotonin Receptor Agonists,
pubmed-meshheading:9632357-Structure-Activity Relationship
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Benzylimidazolines as h5-HT1B/1D serotonin receptor ligands: a structure-affinity investigation.
|
| pubmed:affiliation |
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0540, USA.
|
| pubmed:publicationType |
Journal Article,
In Vitro
|