Tautomerism in drug discovery

Abstract

The influence of tautomerism on the precise structure of drugs and thus of their potential to interact with biological systems is discussed from thermodynamic and kinetic aspects. The types of tautomerism encountered in the structure of drugs in current use are surveyed together with the effect of pH, solvent polarity, and temperature.

Tautomerism in drugs with benzimidazole carbamate moiety: an electronic structure analysis

“…Considering the importance of the tautomerism in drug molecules in the recent past [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], the current results on the tautomerism of benzimidazole carbamates drugs may gain importance.…”

“…Understanding the atomic level information regarding the drug molecules helps the pharmaceutical scientist in the design of new molecules and development (so as to overcome the shortcomings associated with drugs) of the existing drug molecules in different areas of pharmaceutical research-(1) Molecular pharmaceutics scientists to generate new polymorphs to improve the solubility and Several groups highlighted the role of tautomeric preferences of drugs [26][27][28][29][30][31][32]. Our group reported the detailed electronic structure studies, conformational and tautomeric preferences on aminoguanidine, biguanide, guanylthiourea, sulfonylurea, and guanylurea derivatives, which are therapeutically important [33][34][35][36][37][38][39][40][41].…”

Tautomerism in o-hydroxyanilino-1,4-naphthoquinone derivatives: Structure, NMR, HPLC and density functional theoretic investigations

“…Tautomeric equilibrium are strongly affected by polarity of the solvent and density. The accompanied energy difference up to 20 kcal mol À1 can be observed which can alter the concentration of either of the tautomers significantly [1,2]. Isomerisation of prototrophic tautomers refers to the migration of proton from atom to another such as C, N, O or may be S. The migration of such proton involving carbon atom being sufficiently slow so that the corresponding tautomers could be separated easily in solution.…”

“…All compounds exist as 'ortho' and 'para' tautomers in polar solvent such as DMSO-d 6 , however only the 'para' tautomer exists as stable form in the less polar CD 3 CN. 1 H and 13 C chemical shifts were assigned by gDQCOSY, gHSQCAD NMR experiments and by density functional theory (DFT) on the theoretical front.…”

pKa based protonation states and microspecies for protein–ligand docking

“…In this issue the problems of tautomerism in general [11,12], the problem of creating tautomer structures [13][14][15][16] and their use in drug design [17][18][19], especially in QSAR [14,20,21] and virtual screening [15] as well as the problems of tautomerism in large chemical databases [22] are noted. Another review about tautomers in drug design was given earlier by Martin [23].…”