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

Abstract

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.Key words phosphorylated guanidine; 2-aminopyridin-3-ol; anti-inflammatory activity Compounds containing a guanidine functional group exhibit many biological, chemical and medicinal applications.

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

“…These bioactive compounds exhibit a variety of pharmaceutical properties such as anticancer agent [22] , HIV protease inhibitor [ 23 , 24 ], anti-malarial [25] , histamine H2 receptor antagonist [26] , anti-hepatitis [27] , antimicrobial [28] , fungicidal [29] , anti-malarial [25] , and anti-inflammatory [28] . Some research proves that phosphorylation of various drugs may be able to increase their biological activity [30] . There are compounds containing phospho guanidine and phospho pyrazine which represent agricultural and medicinal applications.…”

Copper-Catalyzed N-Cyanation of Sulfoximines by AIBN

“…The N–CN bonds are ubiquitous and frequently found in innumerable natural products, biologically active molecules, and medicinally relevant structures (Scheme ). − For example, sulfoxaflor and thiacloprid play key roles in insecticide field. , Inhibitors of cathepsin K show efficiency on bone resorption, while inhibitors of cathepsin C are utilized in neutrophil-dominated inflammatory diseases . Meanwhile, cyanamides are not only employed as ligands in coordination chemistry − but also the key intermediates leading to guanidines − and heterocycles. − Moreover, as a safe cyanide source, cyanamides were widely applied in the cyanation reaction. − …”

An Efficient Synthesis and In Vitro Antimicrobial Screening of 2-Cyanoimino -4-aryl-6-(1,1'-biphenyl-4-yl)-3,4-dihydro-1H-Pyrimidines

“…In this connection, cyanamides are well documented and are especially embedded in heterocyclic framework are an important structural unit of valuable synthetic intermediates for many medicinally relevant drugs such as diazepam, cyanoquanidine etc. Cyanamino pyrimidine contains N-cyanoguanidyl moiety in its structure and the cyanoguanidine moiety in organic cyanamides found in wide range of biological activities and chemical applications such as neuronal Na + and Ca 2+ channel blockers, glutamate release inhibitors, HIV-1 protease inhibitors, histamine H 3 receptor antagonists etc 16 . Here we have constructed the cyanoimino pyrimidine moiety by using Cyano guanidine as the novel reagent via the following route.…”