Topic : 'Dabigatran is a relatively new oral anticoagulant. Discuss the medicinal chemistry of the compound including its physiochemical properties, pharmacophore and mode of action' - Literature review Example

Download file to see previous pages It is then absorbed into the blood. This drug is converted into active form by the enzymes at GI tract, blood and liver. Oral bioavailability of the drug is 5% and the half life of the drug is 12 hours. It is eliminated from the body through kidney. There are no dietary restrictions to this drug and their interactions with food and other drugs are very less. Thus it is safe for use as a medicine. (Colman 2006).
Figure 2: Structure of the active molecule Dabigatran. It is ionized completely and has both positive and negative charges. The prodrug is 95% unionized at intestine pH. On conversion into the active metabolite, the Amidine group is 99.9% ionized, similarly the acid (COOH) group is 99% ionized. The distribution coefficient value of the prodrug is 10 times higher than the drug badigatran. (Rautio 2011).
Chemical Name: Ethyl 3 - { [2 - ( { 4- [(Z) - amino ­(hexyl­oxycarbonyl­imino)­methyl]­aniline } methyl) – 1 - methyl­benzimidazole-5-carbonyl]­ pyridin-2-yl­amino}­propano­ate tetrahydrate, C34H41N7O5·4H2O. (Coonolly et al. 2009).
Dabigatran contains an ethyl group at the carboxylic acid and a side chain of hexyloxycarbonyl at the amidine. There is a tri substituted benzimidazole derivative with a benzamindine moiety. This moiety forms a salt bridge with the carboxylate of the aspartate enzyme residue Asp 189. It also adds the carboxylic acid. Dabigatran is a polar and charged molecule. This molecule is not available after administration due to its pH range. Dabigatran is formed from two molecules. It is generated with amidinium moiety with a carbamate ester. The carboxylate group binds to the ester group. The two groups are held together by the hydrolytic cleavage. This pro drug has bioavailability of 7%. Dabigatran attaches to thrombin and cleaves the bonds after arg and lys and converts fibrinogen into fibrin. This activates the factors V, VII, VIII, XIII and also the thrombomodulin protein C. (Drug Bank 2012). ...Download file to see next pagesRead More