Antifibrinolytic activity of nicotinic acid conjugates with 6-aminohexanoic, p-aminomethylbenzoic, and trans-4-aminomethylcyclohexanecarboxylic acids

activity of 6-aminohexanoic acid (I), p-aminomethylbenzoic acid (II), trans-4-aminomethylcyclohexanocarboxylic acid (III) ~, and their analogs have been covered in a wide range of literature that offers data on biological actionstructure relationships and a qualitative analyses of the contribution made by some functional groups to overall inhibitory activity [6]. It has been shown in particular that the presence of free amino and carboxyl groups separated by a distance of 0.7 nm is an important condition for the high level of antiproteolytic activity of this group of substances [9]. For the purpose of obtaining potential medicinal agents from compounds I-III, we undertook the synthesis of a number of their vitamin conjugates. Because of the vitamin presence in their molecular composition, we believed such compounds would be less toxic, exhibit a high degree of organotropy, as well as concomitant vitamin activity, and might also have better pharmacokinetic characteristics. That supposition has been recently justified by the production of vitamin conjugates with y-aminobutyric acid [3, 7]. The present work cites results of studies on the antifibrinolytic activity of N-amide derivatives of nicotinic acid with substances of compounds I-III as compared to I. N-nicotinoyl-6-a minohexanoic acid (IV), p-aminomethylbenzoic acid (V), and trans-4-aminomethylcyclohexanecarboxylic acid (VI) ~Jere synthesized by the condensation of nicotinic acid chloroanhydride with salts of the corresponding acids in a water medium with a relatively low yield. This was apparently due to the partial hydrolysis of the chloroanhydride in the Schotten--Baumann reaction: