Synthesis of Novel Phosphorylated Guanidine Derivatives from Cyanamide and Their Anti-inflammatory Activity

A series of novel guanidine derivatives were synthesized in three steps and their anti-inflammatory activities in vitro and in vivo evaluated. 2-Aminopyridin-3-ol (1) was reacted with thiophosphoryl chloride (2) to give a monochloride (3). It was further reacted with cyanamide to afford the corresponding cyanamine (4), which was subsequently reacted with different heterocyclic amines to form the title compounds (5a-l). The substituent in the guanidine function affected the potency of anti-inflammatory activity. The compounds having benzothiazole, fluorophenyl, and piperazinyl moieties enhanced the anti-inflammatory activity. Compounds containing a guanidine functional group exhibit many biological, chemical and medicinal applications.1) Guanidine is a ubiquitous group in natural products and plays a key role in many biological activities.2) In peptides, guanidine, a residue of L-arginine, exists in the protonated form as guanidinium ions functioning as an efficient recognition moiety of anionic substrates such as carboxylate, phosphate and intonate functionalities.