Anthranilic acid based CCK1 receptor antagonists: preliminary investigation on their second “touch point”

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

“…This hypothesis is supported by previous SAR study regarding the importance of the Phe phenyl ring of VL-0395 showing that the π-system and therefore the electrostatic potential of the aromatic ring is irrelevant for the receptor recognition . In this regard, a recent study of Wilcox and co-workers highlights how no electronic effect was involved in edge-to-face interactions, suggesting in contrast an important role of London dispersion forces …”

“…17 This hypothesis is supported by previous SAR study regarding the importance of the Phe phenyl ring of VL-0395 showing that the π-system and therefore the electrostatic potential of the aromatic ring is irrelevant for the receptor recognition. 18 this regard, a recent study of Wilcox and co-workers highlights how no electronic effect was involved in edge-to-face interactions, suggesting in contrast an important role of London dispersion forces. 19 Further examination of the K i values obtained for VL-0395 and for the other anthranilic derivatives, according to the "three ligand concept" 20 and therefore on thermodynamic basis, suggests that these compounds have at least two "touch points" with the CCK 1 -R(1-47) fragment.…”

Strategies for Design of Non Peptide CCK1R Agonist/Antagonist Ligands

“…From the study of N-terminal modified compounds, it was evident that every single modification of the 2-indole moiety caused a decrease in CCK1R binding affinity, indicating a key role of this substituent for the interaction with the receptor [55]. On the contrary, modifications of the C-terminal Phe residue are much more flexible and productive, being possible not only the enhan-cement of CCK1R affinity, but also the possibility of reversing the selectivity for CCK2R within the same family of compounds [56]. Compound 26, Fig.…”

“…The antagonist nature of this compound was confirmed by the inhibition of the guinea pig gallbladder contraction induced by CCK-8 in vivo, with a potency (ED 50 = 0.38 μmol/kg) similar to that exhibited by loxiglumide in the same assay. To investigate the precise requirements of the N-and C-terminal pharmacophore groups, they prepared and tested on CCK receptors two small libraries of analogues of 25 [55,56]. From the study of N-terminal modified compounds, it was evident that every single modification of the 2-indole moiety caused a decrease in CCK1R binding affinity, indicating a key role of this substituent for the interaction with the receptor [55].…”

A Calorimetric and Computational Study of Aminomethoxybenzoic Acids

“…Aminobenzoic acids and their derivatives are useful intermediates for producing pharmaceuticals, aromatic compounds absorbing UVB and/or UVA, dyes, and flavours and fragrances . Conducting polymers, nanocrystalline particles, materials with luminescent characteristics, peptides and peptidomimetics, and other molecules with biological properties − are also built from these aromatic amino acids. Aminomethoxybenzoic acids are trisubstituted benzene compounds with the general structure shown in Figure and will generally be referred to as XA−Y−MOBA, where X represents the position of the amino group A; Y represents the position of the methoxy group MO; and BA is the acronym for benzoic acid.…”