Guanidines from ‘toxic substances’ to compounds with multiple biological applications – Detailed outlook on synthetic procedures employed for the synthesis of guanidines

Tahir, Shaista; Badshah, Amin; Hussain, Raja Azadar

doi:10.1016/j.bioorg.2015.01.006

Cited by 42 publications

(16 citation statements)

References 260 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Essentially, the simplest unit in the three molecules is the guanidine polyamine group (Figure ). This unit is both biologically multiactive and synthetically versatile that could be readily derivatized via the circled N ‐atoms (Figure ; Katritzky, Tala, & Singh, ; Tahir, Badshah, & Hussain, ). The biguanide core, which is a merger of two guanidine units, is capable of eliciting a myriad of pharmacological effects via hydrogen bonding and ionic interactions with its receptors, at physiologic pH (Langmaier, Pizl, Samec, & Zalis, ; Saczewski & Balewski, ; Tahir et al, ).…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

“…This unit is both biologically multiactive and synthetically versatile that could be readily derivatized via the circled N ‐atoms (Figure ; Katritzky, Tala, & Singh, ; Tahir, Badshah, & Hussain, ). The biguanide core, which is a merger of two guanidine units, is capable of eliciting a myriad of pharmacological effects via hydrogen bonding and ionic interactions with its receptors, at physiologic pH (Langmaier, Pizl, Samec, & Zalis, ; Saczewski & Balewski, ; Tahir et al, ). Although hydrogen bonding also contributes to the hydrophilic nature of biguanides, their characteristically high pKa (>12) leads to: mono‐ or di‐protonation at physiological pH and N ‐atom reactions with acids like HCl to make highly water soluble salts (Langmaier et al, ).…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

See 1 more Smart Citation

A review of phenformin, metformin, and imeglimin

Yendapally

Sikazwe

Kim

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

Diabetes mellitus is a serious metabolic disorder affecting millions of people worldwide. Phenformin and metformin are biguanide antidiabetic agents that are conveniently synthesized in a single-step chemical reaction. Phenformin was once used to lower blood glucose levels, but later withdrawn from the market in several countries because it was frequently associated with lactic acidosis. Metformin is still a widely prescribed medication for the treatment of type 2 diabetes despite the introduction of several newer antidiabetic agents. Metformin is administered orally and has desirable pharmacokinetics. Incidence of metformin-induced lactic acidosis is serious but very rare. Imeglimin, a novel molecule being investigated by Poxel and Sumitomo Dainippon Pharma in Japan, is currently in clinical trials for the treatment of type 2 diabetes. Unlike metformin, imeglimin is a cyclic molecule containing a triazine ring.However, like metformin, imeglimin is also a basic small molecule. Imeglimin is synthesized from metformin as a precursor via a single step chemical reaction. Recent mechanism of action studies suggests that imeglimin improves mitochondria function, when given in combination with metformin it helps achieve better glycemic control in patients with type 2 diabetes. We herein describe and compare the current status, synthesis, physicochemical properties, pharmacokinetic parameters, mechanism of action, and preclinical/clinical studies of metformin and imeglimin.

show abstract

Section: Physicochemical Propertiesmentioning

confidence: 99%

Section: Physicochemical Propertiesmentioning

confidence: 99%

A review of phenformin, metformin, and imeglimin

Yendapally

Sikazwe

Kim

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…This partial protonation lowers their overall polarity (Log P octanol/water ), which may be beneficial for their biodistribution, as highly polar guanidines suffer from poor membrane permeability . Hence, their application as bioisosters of guanidines received attention in medicinal chemistry to increase uptake and improve biodistribution, thereby improving the efficacy of many guanidine‐based drugs . These interesting features have led us to explore the utilization of methyl ester functional PAOx for the acylation of guanidines.…”

Section: Introductionmentioning

confidence: 99%

Acyl guanidine functional poly(2‐oxazoline)s as reactive intermediates and stimuli‐responsive materials

Guyse

Hoogenboom

2019

J. Polym. Sci. Part A: Polym. Chem.

View full text Add to dashboard Cite

The many postpolymerization modification opportunities of biocompatible poly(2‐alkyl/aryl‐2‐oxazoline)s (PAOx), such as thiol–ene/thiol–yne, azide–alkyne cycloadditions, amidation, and transesterification, are one of the most appealing features of this polymer class for its popularity in biomedicine. Inspired by recent reports on guanidine‐catalyzed transesterification and amidation reactions of methyl ester substrates, we explored the use of guanidines as a reactant for the modification of methyl ester functional PAOx, to obtain the respective acyl guanidines. The obtained acyl guanidines functional polymers display reactivity toward α‐haloketones, yielding imidazole functional PAOx. The obtained polymer structures are protonated in a broad pH range, and the acyl guanidine moiety is demonstrated to be a cleavable linker under basic conditions. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2616–2624

show abstract

“…8 S-Oxidized thiourea derivatives 9 and guanylating agents 10 (such as S-methylisothioureas, pyrazole-1-carboximidamide and its derivatives, or triflyl guanidines) are also commonly employed. Beyond the well-known 11 and recently 12 developed approaches, a few isocyanide-based procedures have also been established, albeit each method exclusively affords N,N′,N″-substituted guanidines. 13 Looking at the synthetic toolbox for the assembly of N,N′-disubstituted guanidines, N-protected S-methylisothioureas are often used as starting materials; however, the techniques available for the derivatization of isothioureas lack the achievable diversity (Scheme 1a).…”

Section: Introductionmentioning

confidence: 99%