Anthranilic Acid Based CCK₁ Receptor Antagonists and CCK-8 Have a Common Step in Their “Receptor Desmodynamic Processes”

Abstract

The interaction between the 1-47 N-terminus of the CCK(1)-R and the anthranilic acid based antagonists has been investigated by fluorescence spectroscopy. These antagonists interact with W39 of the N-terminal domain of the CCK(1)-R like that of the endogenous ligand CCK-8. This specific interaction was not found in other nonpeptide ligands of the CCK(1)-R. Conformational studies, using NMR and energy minimization procedures, have allowed formulation of a new hypothesis on the CCK(1)-R binding mode of the anthranilic antagonists.

Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation

“…The activities of N-methyl amide derivatives (19)(20)(21) vanished due to removal of the intramolecular hydrogen bond, which results in a drastic loss of binding affinity. 37 Furthermore, except for 23, exchanges in the benzene rings (A or B rings) of 1 by different isosteric replacements (22)(23)(24)(25)(26)(27) were unfavorable. There are many reports that demonstrate that replacing the CH with an N at each of the aromatic sites leads to improved aqueous solubility, preserves hydrogen bonding, or reduces metabolism.…”

“…White powder, mp 74-76 • C. 1 H NMR (CDCl 3 ) d 12.00 (1H, d, J = 8.0 Hz, NH), 9.21 (1H, s, H-2), 8.81 (1H, d, J = 6.0 Hz, H-6), 8.66 (1H, d, J = 6.0 Hz, H-5), 8.07 (1H, td, J = 8.4, 1.6 Hz, H-6¢), 7.54 (1H, ddd, J = 13.2, 8.4, 1.6 Hz, H-4¢), 7.30 (1H, t, J = 8.4 Hz, H-5¢), 7.22 (1H, dd, J = 11.2, 8.4 Hz, H-3¢), 4.46 (2H, q, J = 6.8 Hz, OCH 2 CH 3 ), 1.44 (3H, t, J = 6.8 Hz, OCH 2 CH 3 ). 13 (24). Compound 24 was synthesized in 58% yield from 2-aminonicotinic acid (2d) in a procedure similar to 8.…”

“…Anthranilic acid derivatives have been recognized to have diverse biological activities, [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] in particular, they are enzymatic inhibitors of VEGF receptor kinase, 14 matrix metalloproteinase (MMP), 15 acyl carrier protein synthase (AcpS), 16 methionine aminopeptidase-2, 17,18 phospholipase A 2 , 19 human hydroxysteroid dehydrogenase AKR1C1, 20 plasminogen activator inhibitor-1, 21 and cholecystokinin (CCK). [22][23][24] In addition, they also exhibit anti-cancer, anti-hepatitis C virus (anti-HCV), anti-Alzheimer, anti-inflammatory, anti-platelet, and anti-bacterial activities. [25][26][27][28][29][30][31][32][33][34][35] Of these, the N-phenylanthranilic acids, e.g.…”

Strategies for Design of Non Peptide CCK1R Agonist/Antagonist Ligands

“…Anthranilic acid-derived CCK1R antagonists. derivatives with the receptor fragment CCK1R(1-47), selected as a receptor model [57]. This study pointed out to an interaction between the non-peptide ligands and Trp 39 residue of the N-terminal extracellular domain of CCK1R.…”

Exploring the Dual Inhibitory Activity of Novel Anthranilic Acid Derivatives towards α-Glucosidase and Glycogen Phosphorylase Antidiabetic Targets: Design, In Vitro Enzyme Assay, and Docking Studies

“…Therefore, glucosidase is a therapeutic target for many types of antidiabetic drugs having inhibitory activity against it, such as acarbose, miglitol, and voglibose, which are used in clinic for treatment of type 2 diabetes [ 22 ]. Recently, the molecules that were based on anthranilic acid scaffold have gained much attention in drug discovery and development [ 23 , 24 , 25 ]. Anthranilic acid and its derivatives are constituents of many bioactive molecules.…”