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Acylguanidines as bioisosteric groups in argininamide-type neuropeptide Y Y1 and Y2 receptor antagonists: synthesis, stability and pharmacological activity

URN to cite this document: urn:nbn:de:bvb:355-opus-7423

Brennauer, Albert (2006) Acylguanidines as bioisosteric groups in argininamide-type neuropeptide Y Y1 and Y2 receptor antagonists: synthesis, stability and pharmacological activity. PhD, Universität Regensburg

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Abstract (English)

We developed multi-step synthetic routes for the preparation of two classes of N(G)-substituted argininamides with neuropeptide Y Y1 and Y2 receptor selective antagonistic activity, respectively. In both series we could identify N(G)-acylated analogs being even more potent than the respective N(G)-unsubstituted compounds, which are established as standard Y1- (BIBP 3226) and Y2-antagonists (BIIE 0246) in literature. Moreover, the introduction of acyl substituents in N(G)-position led to compounds with reduced basicity and thus improved pharmacokinetic properties, which allows for their application as versatile pharmacological tools for the in vivo and in vitro characterization of Y1- and Y2-receptors.

Translation of the abstract (German)

Wir beschäftigten uns mit der Synthese von zwei verschiedenen Klassen von N(G)-substituierten Argininamiden mit Neuropeptid Y Y1- bzw. Y2-rezeptorselektiver antagonistischer Wirkung. In beiden Serien fanden sich N(G)-acylierte Analogverbindungen, die potenter sind als die entsprechenden unsubstituierten Verbindungen BIBP 3226 und BIIE 0246, die als Standard Y1- bzw. Y2-Rezeptorantagonisten in der Literatur etabliert sind. Darüber hinaus führte die Einführung von Acylsubstituenten am Guanidinstickstoff zu Verbindungen mit verminderter Basizität und damit günstigeren pharmakokinetischen Eigenschaften, was die N(G)-acylierten Argininamide zu wertvollen pharmakologischen Werkzeugen für die in vivo und in vitro Charakterisierung von Y1 und Y2 Rezeptoren macht.

Item Type:Thesis of the University of Regensburg (PhD)
Referee:Prof. Dr. Armin Buschauer
Date of exam:11 September 2006
Institutions: Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)
Keywords:Neuropeptid Y , Pharmakologischer Antagonist , Argininderivate , Guanidinderivate , Peptidomimetikum , Organische Synthese , Amide , Chemische Synthese , Rezeptor , NPY Rezeptoren , Y1 Rezeptor , Y2 Rezeptor , BIBP 3226 , BIIE 0246 , Guanidinylierung , NPY receptors , Y1 receptor , Y2 receptor , BIBP 3226 , BIIE 0246 , guanidinylation
Subjects:500 Science > 540 Chemistry & allied sciences
Status:Published
Refereed:Yes, this version has been refereed
Created at the University of Regensburg:Yes
Owner:Universitätsbibliothek Regensburg
Deposited On:27 Oct 2009 08:52
Last Modified:20 Jul 2011 23:59
Item ID:10487
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