|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
17
|
|
pubmed:dateCreated |
2001-8-9
|
|
pubmed:abstractText |
A small series of 4-fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines (4-fluoro-THBAs; 12-15) were synthesized and evaluated as inhibitors of phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) and as inhibitors of the binding of clonidine at the alpha(2)-adrenoceptor. 4-Fluoro-THBAs 13-15 displayed selectivity ratios (alpha(2) K(i)/PNMT K(i)) greater than 75 and 4-fluoro-8-nitro-THBA (13) was found to be one of the most selective inhibitors of PNMT known, with a selectivity ratio of greater than 900. These compounds are also quite lipophilic and according to previous results from this laboratory should be able to penetrate the blood-brain barrier. These 4-fluoro-THBAs represent important leads in the development of new, more selective, CNS-active inhibitors of PNMT.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0022-2623
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
16
|
|
pubmed:volume |
44
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2849-56
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:11495596-Adrenergic alpha-Antagonists,
pubmed-meshheading:11495596-Animals,
pubmed-meshheading:11495596-Benzazepines,
pubmed-meshheading:11495596-Cerebral Cortex,
pubmed-meshheading:11495596-Clonidine,
pubmed-meshheading:11495596-Enzyme Inhibitors,
pubmed-meshheading:11495596-Male,
pubmed-meshheading:11495596-Models, Molecular,
pubmed-meshheading:11495596-Phentolamine,
pubmed-meshheading:11495596-Phenylethanolamine N-Methyltransferase,
pubmed-meshheading:11495596-Radioligand Assay,
pubmed-meshheading:11495596-Rats,
pubmed-meshheading:11495596-Rats, Sprague-Dawley,
pubmed-meshheading:11495596-Receptors, Adrenergic, alpha-2,
pubmed-meshheading:11495596-Structure-Activity Relationship
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Synthesis and evaluation of 4-fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as selective inhibitors of phenylethanolamine N-methyltransferase versus the alpha(2)-adrenoceptor.
|
|
pubmed:affiliation |
Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, USA. ggrunewald@ukans.edu
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
