Attempts of activating carboxylic group of 3‐amine‐1H‐pyrazole‐5‐carboxylic acid using azide method

Despite the fact that this system is weakly represented in nature [1÷5], the pyrazole is well-known pharmacophore [6] and plays important role for broad-spectrum drugs. The derivatives containing pyrazole structure belong to group of antibiotics used against viral families containing RNA or DNA genome, such as e.g. HIV. Moreover, they are used as analgesic and anti-inflammatory drugs [1] and also show antitumor [7, 8], antifungal and antibacterial activity [9÷11]. They are also studied as anticonvulsants [12÷14], antiparasitics [15], anorectics [16], immunosuppressant [17], hepatoprotectants [18], hypoglycemics [19÷21] and antiatherosclerotics [22]. Recently the derivative of 3-aminopyrazole has been also applied in the synthesis of compounds for DNA recognition, i.e. lexitropsins [23] and also for drug design for conformational diseases [24÷32], due to its ability to form hydrogen bonds stabilizing protein conformation. The studies on small non-peptide ligands, started in 1990s have shown that 3-aminopyrazole might stabilise β-sheet conformation of peptides via hydrogen bonds that form almost linear systems of two donors and one acceptor bond (DAD – donor-acceptor-donor). These bonds involve peptide chain, both top and bottom part. The additional benefits of molecule of 3-aminopyrazole is that while bonding with peptide from one side, it cannot form bonds from the other side with other chain and therefore it can prevent Aβ aggregation into β-amyloid deposits [24, 25, 27, 30, 31].