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Abstract
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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
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