Add time:09/10/2019 Source:sciencedirect.com
NG-Acylated argininamides, covering a broad range of lipophilicity (calculated log D values: −1.8–12.5), were synthesized and investigated for NPY Y1 receptor (Y1R) antagonism, Y1R affinity and stability in buffer (NG-deacylation, yielding BIBP 3226). Broad structural variation of substituents was tolerated. The Ki (binding) and Kb values (Y1R antagonism) varied from low nM to one-digit μM. Most of the compounds proved to be sufficiently stable at pH 7.4 over 90 min 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.
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