Oxygenated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are potent dopamine receptor antagonists, preferentially at D1/D5. We synthesized the hydroxylated, methoxylated, and chlorinated 11-membered and 12-membered homologues of these 10-membered heterocycles. Their affinities for the human cloned D1-D5 receptors (radioligand binding) and functionalities (calcium assay) were measured. Enlarging the dibenzazecines to the corresponding dibenzazacycloundecenes and dibenzazacyclododecenes generally maintains the high antagonistic affinity for D1/D5 but also leads to a compound with a clozapine-like binding profile due to additional affinity for D4.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm070388+ | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into the biosynthesis of 12-membered resorcylic acid lactones from heterologous production in Saccharomyces cerevisiae.
ACS Chem Biol
May 2014
Biotechnology Research Institute, Chinese Academy of Agricultural Sciences , 12 Zhongguancun South St., Beijing 100081, People's Republic of China.
The phytotoxic fungal polyketides lasiodiplodin and resorcylide inhibit human blood coagulation factor XIIIa, mineralocorticoid receptors, and prostaglandin biosynthesis. These secondary metabolites belong to the 12-membered resorcylic acid lactone (RAL12) subclass of the benzenediol lactone (BDL) family. Identification of genomic loci for the biosynthesis of lasiodiplodin from Lasiodiplodia theobromae and resorcylide from Acremonium zeae revealed collaborating iterative polyketide synthase (iPKS) pairs whose efficient heterologous expression in Saccharomyces cerevisiae provided a convenient access to the RAL12 scaffolds desmethyl-lasiodiplodin and trans-resorcylide, respectively.
View Article and Find Full Text PDFDopamine/serotonin receptor ligands. 16.(1) Expanding dibenz[d,g]azecines to 11- and 12-membered homologues. Interaction with dopamine D(1)-D(5) receptors.
J Med Chem
September 2007
Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany.
Oxygenated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines are potent dopamine receptor antagonists, preferentially at D1/D5. We synthesized the hydroxylated, methoxylated, and chlorinated 11-membered and 12-membered homologues of these 10-membered heterocycles. Their affinities for the human cloned D1-D5 receptors (radioligand binding) and functionalities (calcium assay) were measured.
View Article and Find Full Text PDFCharacterization of tylM3/tylM2 and mydC/mycB pairs required for efficient glycosyltransfer in macrolide antibiotic biosynthesis.
J Am Chem Soc
December 2004
Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712, USA.
The heterologous expression of tylM3 and mydC, two homologous genes of previously unknown function, along with genes encoding their respective partner glycosyltransferases, tylM2 and mycB, and the necessary sugar biosynthesis genes significantly enhances the glycosyltransferase activity in the engineered Streptomyces venezuelae host in which the native glycosyltransferase, desVII, has been inactivated. Both glycosyltransferases accept the endogenous 12-membered macrolide, 10-deoxymethynolide, or the exogenously fed 16-membered macrolide, tylactone. Five new compounds were generated using this expression system.
View Article and Find Full Text PDFSynthesis, receptor binding affinities and conformational properties of cyclic methylenedithioether analogues of angiotensin II.
Bioorg Med Chem
March 2001
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University, Sweden.
Cyclic 12-, 13- and 14-membered ring angiotensin II analogues related to disulfides but encompassing methylene-dithioether bridges have been prepared. The affinity data from these derivatives were compared to those from the disulfides. The methylenedithioether analogues displayed good binding affinities to rat liver AT1 receptors although in most cases somewhat lower than their disulfide counterparts.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!