Synthetic accesses to biguanide compounds

Abstract

Biguanide is a unique chemical function, which has attracted much attention a century ago and is showing resurgent interest in recent years after a long period of dormancy. This class of compounds has found broad applications such as reaction catalysts, organic strong bases, ligands for metal complexation, or versatile starting materials in organic synthesis for the preparation of nitrogen-containing heterocycles. Moreover, biguanides demonstrate a wide range of biological activities and some representatives are worldwide known such as metformin, the first-line treatment against type II diabetes, or chlorhexidine, the gold standard disinfectant and antiseptic. Although scarcely represented, the number of “success stories” with biguanide-containing compounds highlights their value and their unexploited potential as future drugs in various therapeutic fields or as efficient metal ligands. This review provides an extensive and critical overview of the synthetic accesses to biguanide compounds, as well as their comparative advantages and limitations. It also underlines the need of developing new synthetic methodologies to reach a wider variety of biguanides and to overcome the underrepresentation of these compounds.

Poly(hexamethylene biguanide) hydrochloride (PHMB)-based materials: synthesis, modification, properties, determination, and application

“…The starting materials for these methods are either amines or guanidines to yield symmetric or asymmetric biguanides. 2 A series of biguanide derivatives with versatile properties, such as metformin and chlorhexidine, can be synthesized by incorporating apolar aryl or alkyl groups to the main chain. In other words, the synthesis of biguanide derivatives is tailorable depending on the nature and degree of substitution and the desired properties of the targeted compounds.…”

“…Biguanide, first discovered by Rathke in 1879 via chemical synthesis using cyanimide and guanidine, is a nitrogenous organic compound comprising two guanidine units linked by a common nitrogen atom. [1][2][3] The unique features of biguanide, such as superb hypoglycemic, antiseptic, antimicrobial, and antimalarial properties, enable it to be extensively used for pharmaceutical applications. 3,4 Historically, studies involving biguanide experienced a long period of dormancy due to some known toxicity.…”

Heterocyclic compounds as a magic bullet for diabetes mellitus: a review

“…A number of synthetic drugs are available in market that had their great potential in order to cure diabetes as metformin, 132 gliquidone, 133 nateglinide, 134 phenformin, 135 rosiglitazone, 136 glimepiride, 137 pioglitazone, 138 glibenclamide, exenatide, 139 mitiglinide, 140 gliclazide, 141 chlorpropamide, 142 glipizide, 143 acetohexamide, 144 tolbutamide, 145 dapagliflozin, 146 dulaglutide, 147 liraglutide, 148 glyburide, 149 canagliflozin, 150 and repaglinide. 151 Some therapeutic agents are used to cure DM, classified as α-glycosidase inhibitors, thiazolidinediones, 5,152 biguanides, 153 sulfonylureas, 154 and gliptins. 155 Deazaxanthine 156 and also various heterocyclic synthetic based pyrrole, 157 pyrazole, 158 pyrrolidine, 159 oxindole, 160 isatin, 161 imidazole, 162 benzimidazole, 163 triazole, 164 oxadiazole, 165 thiazole, 166 pyridine, 167 piperazine, 168 thiazolidinone, thiadiazole, 169 benzofuran, 170 benzoxazole, 171 coumarin, 172 flavone, 173 piperidine, 174 xanthone 175 and pyrimidine.…”

Screening-enhanced effect enables poly(hexamethylene biguanide) hydrochloride to effectively overcome charge screening limitations

“…The significant HOMO-LUMO energy gap of PHMB also favors its stable chemical skeleton and thermal stability 9 . Also, the biguanide group has three tautomeric resonance forms, which implies that biguanide-bearing cationic polyelectrolytes, including PHMB, have high proton mobility and pH-tolerant properties owing to the delocalization of charges [10][11][12] . It has been confirmed by our preliminary study in which PHMB possesses remarkable screening-enhanced effect (Figs.…”