Quantitative structure-activity relationships

Indole amide derivatives: synthesis, structure–activity relationships and molecular modelling studies of a new series of histamine H1-receptor antagonists

“…For a better and wider definition of structure-activity relationships (SAR), we also considered compounds in which the distance between the aromatic moiety (indole nucleus) and the cationic centre was varied by substitution of the oxalylamide group COCONH with a carboxyamide residue CONH, bound at position 3 (compounds 29-43) or 2 (compounds 48-56) of the indole system. It is interesting to note that there are a number of examples in literature of non-classic H 1 -antagonists, in which one of the aromatic groups is separated from the cationic centre by means of an intermediate chain CON-H(CH 2 ) 2 [21,22]. Derivatives in which the aminoethylamide chain at position 3 of the indole nucleus was inserted into a piperazine ring (compounds 57-59) were also prepared.…”