296282-22-9Relevant academic research and scientific papers
C-terminal anthranoyl-anthranilic acid derivatives and their evaluation on CCK receptors
Varnavas, Antonio,Lassiani, Lucia,Luxich, Elena,Valenta, Valentina
, p. 293 - 302 (2000)
A series of C-terminal anthranoyl-anthranilic acid derivatives arising from a strict bond disconnection approach of asperlicin were synthesized and examined for their CCK receptor affinities. These compounds represent the second step of our investigation
New anthranilic acid based antagonists with high affinity and selectivity for the human cholecystokinin receptor 1 (hCCK1-R)
Pavan, Michela V.,Lassiani, Lucia,Berti, Federico,Stefancich, Giorgio,Ciogli, Alessia,Gasparrini, Francesco,Mennuni, Laura,Ferrari, Flora,Escrieut, Chantal,Marco, Esther,Makovec, Francesco,Fourmy, Daniel,Varnavas, Antonio
experimental part, p. 5769 - 5785 (2011/10/09)
The anthranilic acid diamides represent the most recent class of nonpeptide CCK1 receptor (CCK1-R) antagonists. Herein we describe the second phase of the anthranilic acid C-terminal optimization using nonproteinogenic amino acids containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797) enhanced 12-fold the affinity for the rat CCK1-R affinity and 15-fold for the human CCK1-R relative to the reference compound 12 (VL-0395). The eutomer of 2 (6) exhibited a nanomolar range affinity toward the human CCK1-R and was at least 400-fold selective for the CCK1-R over the CCK2-R. Molecular docking in the modeled CCK1-R and its validation by site-directed mutagenesis experiments showed that the 6 binding site overlaps that occupied by the C-terminal bioactive region of the natural agonist CCK. Owing to their interesting properties, new compounds provided by this study represent a solid basis for further advances aimed at synthesis of clinically valuable CCK1-R antagonists.
