Guanidine pharmacophore points

The requirement of two distinct pharmacophore points neglects at least one very important class of drugs biogenic amine-containing CNS drugs. Therefore, a second pharmacophore filter has been designed that requires only one pharmacophore point in small molecules of the type amine, amidine, guanidine, or carboxylic acid (PF2). 

The considered functional groups are those having some hydrogen-bonding capabilities that are essential for specific drug interactions with the target. These are called pharmacophore points and include amine, amide, alcohol, ketone, sulfone, sulfonamide, carboxylic add, carbamate, guanidine, amidine, urea, and ester. 

In a modified version of the pharmacophore point filter, a score equal to 1 is allowed to qualify a compound as drug-like if the pharmacophore point present in the compound is of type carboxylic acid, amine, guanidine, or amidine. This modified filter was defined to correctly classify the small active drugs belonging to the central nervous system (CNS) class. 

Tinti and Noffe observed that the combination of the cyano analogue of suosan with the elements of asparatame yields superaspartame which has a potency 14 (KX) times that of sucrose (aspartame has a potency of about 180 times that of sucrose. Fig. 39.19). Subsequently, these authors discovered sweet guanidines such as the compound SC-45647 which has a potency 28000 times that of sucrose. More recently, they reported iV-alkyl-substi-tuted aspartame derivatives such as neotame which has a potency 10 000 times that of sucrose. For these three high-potency sweeteners, Walters et al. were able to identify a five-point pharmacophore model in which the carboxylate, the two hydrophobic groups and two NH groups match well... 

---