Abdolmohammad Mehranpour

Guanidines are classified as strong organobases with the pKₐ values of the conjugated acids being on the order of 13. Substitution of the nitrogen atoms in guanidine by elec- tron-donating groups such as alkyls or heteroalkyls slightly increases its basicity, while substitution by electron-withdrawing groups such as NO₂, CN, aryl, acyl or sulfonyl, decreases the pKₐ values considerably to about 7–8.¹–⁴ Guanidine, also called carbami- dine, plays a key role in many biological activities. It is not surprising, then, that the guanidine group influences the chemical and physicochemical properties of many com- pounds of medical interest. Sulfadiazine, Trimethoprim, and Gleevec are examples of pharmaceutically important guanidine-containing heterocycles (Fig. 1).⁵–⁹ Compounds containing guanidine functionality have attracted considerable synthetic interest due both to the hydrogen-bond mediated interactions of guanidinium ions and the wide variety of biological activities those substances display.¹⁰–¹²