Weiss, Stefan and Keller, Max and Bernhardt, G. and Buschauer, Armin and König, Burkhard (2010) N(G)-Acyl-argininamides as NPY Y (1) receptor antagonists: Influence of structurally diverse acyl substituents on stability and affinity. Bioorganic & Medicinal Chemistry (18), pp. 6292-6304.
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N(G)-Acylated argininamides, covering a broad range of lipophilicity (calculated logD values: -1.8-12.5), were synthesized and investigated for NPY Y(1) receptor (Y(1)R) antagonism, Y(1)R affinity and stability in buffer (N(G)-deacylation, yielding BIBP 3226). Broad structural variation of substituents was tolerated. The K(i) (binding) and K(b) values (Y(1)R antagonism) varied from low nM to one-digit muM. Most of the compounds proved to be sufficiently stable at pH 7.4 over 90min to determine reliable pharmacological data in vitro. Exceptionally high instability was detected when a succinyl moiety was attached to the guanidine, probably, due to an intramolecular cleavage mechanism.
|Institutions:|| Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König|
Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)
|Projects:||GRK 760, Graduiertenkolleg Medizinische Chemie|
|Keywords:||Acyl guanidines, NPY, BIBP 3226, GPCR|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||20 Oct 2010 08:59|
|Last Modified:||15 Dec 2010 08:17|