Recent developments in guanylating agents

Katritzky, Alan R.; Rogovoy, Borys V.

doi:10.3998/ark.5550190.0006.406

Cited by 143 publications

(48 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Numerous strategies to convert a primary amine into a guanidinium group have been reported and comprehensively reviewed by Katritzky and Rogovoy. 75 Here, we briefly describe the synthetic approaches used in the reports mentioned above (Figure 15 ). For the conversion of aminoglycosides into guanidinoglycosides, we typically use Boc-protected triflylguanidine, a reagent developed by Goodman and co-workers.…”

Section: Guanidinylating Agentsmentioning

confidence: 99%

On Guanidinium and Cellular Uptake

2014

View full text Add to dashboard Cite

Guanidinium-rich scaffolds facilitate cellular translocation and delivery of bioactive cargos through biological barriers. Although impressive uptake has been demonstrated for nonoligomeric and nonpept(o)idic guanidinylated scaffolds in cell cultures and animal models, the fundamental understanding of these processes is lacking. Charge pairing and hydrogen bonding with cell surface counterparts have been proposed, but their exact role remains putative. The impact of the number and spatial relationships of the guanidinium groups on delivery and organelle/organ localization is yet to be established.

show abstract

Section: Guanidinylating Agentsmentioning

confidence: 99%

On Guanidinium and Cellular Uptake

2014

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4][5] With high thermal stability, the ease of charge delocalization and coordination properties as well as the possibility to attach up to six different substituents on the guanidine moiety has driven research activities in diverse directions, resulting in their use as superbases, [6,7] ligands for coordination complexes, [8][9][10][11] organocatalysts, [12][13][14][15][16] stimuli-responsive materials, [17] hydrogels, [18] anion exchange polymer electrolytes for fuel cells, [19] and biologically active compounds [20][21][22][23][24][25][26][27][28][29] for drug development. Furthermore, guanidinium salts have also entered the field of ionic liquid crystals (ILCs) [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] as an alternative cationic head group to the imidazolium-derived ILCs, which have dominated this research area so far.…”

Section: Introductionmentioning

confidence: 99%

Cyanobiphenyl versus Alkoxybiphenyl: Which Mesogenic Unit Governs the Mesomorphic Properties of Guanidinium Ionic Liquid Crystals?

et al. 2014

View full text Add to dashboard Cite

A series of phenylguanidinium salts 3 . X, which are linked via an alkoxy spacer either to a 4-decyloxy-or 4-cyanosubstituted biphenyl mesogen, was prepared and the mesomorphism studied. A decyloxybiphenyl core and a spacer of at least C6 chain length were required for mesophase formation. Replacement of the chloride counterion by other anions like bromide or tetrafluoroborate improved the thermal stability of the mesophase. A comparison of substitution pattern (meta v. para) on the phenyl ring revealed decreased melting and clearing points for the bent cationic head group. All guanidinium ionic liquid crystals 3 displayed only smectic A (SmA) phases. A packing model is assumed where the molecules in a bilayer stack over each other in opposite direction with interdigitated terminal decyloxy groups and spacers.bromides 9 giving the tethered compounds p-10a,b and m-10b-e in 78-88 % yield. N-Boc-deprotection to derivatives p-11a,b and m-11b-e was achieved very cleanly with methane sulfonic acid in CHCl 3 . Derivative m-11a was obtained in 94 % yield by acidic hydrolysis [62] of acetamide m-7a. The aniline derivatives 11 were finally treated with chloro-N,N,N 0 ,N 0tetramethylformamidinium chloride [63] and either NEt 3 or NaHCO 3 . Workup strictly required an inert gas atmosphere to provide the neat target guanidinium salts 3 . Cl in 70-98 % yield. To further study the anion effect, decyloxybiphenyl guanidinium chloride m-3a . Cl was submitted to salt metathesis with NaBr, KI, NaOTf, NaBF 4 , KPF 6 , KOAc, and KSCN yielding the corresponding guanidinium ILCs m-3a . X (Scheme 2). Anion Effect in Guanidinium ILCsComparison of the 1 H NMR spectra of phenylguanidinium salts m-3a . X revealed a significant downfield shift of the N-H signal from ,7.5 to 12.0 ppm in the following order: PF 6 , BF 4 , OTf , I , SCN , Br ECl (Fig. 1).This correlation between the anion and the N-H proton shift indicates the presence of contact between the ion pairs that also led to small chemical shifts of the aromatic protons of the phenylguanidinium moiety (Fig. 1, grey). To estimate the effect of concentration on the N-H signal, 1 H NMR measurements of m-3b . Cl with concentrations varying from 0.83 to 2.50 mg mL À1 were carried out. The N-H signal shift of 0.1 ppm turned out to be negligible with respect to the strong dependence of the NH signal on the anion (see Supplementary Material for details). This effect rather might be due to either the interaction of the anion with the anisotropic cone of the aryl ring than due to the conjugation between the guanidinium cation and the aryl ring. Previous DFT calculations of several guanidinium salts revealed no or only very little conjugation, i.e. the guanidinium moiety behaves like an isolated cation. [39] In agreement with these studies, the N-H signal shifted upfield with increasing anion radii [64,65] with an almost linear correlation (Fig. 2).

show abstract

“…The use of cyanamides as starting material for the preparation of guanidines is a well stablished methodology [33] . Thus, in order to synthesize compounds 3 a – g we obtained the pyrimidine‐bearing cyanamide 5 following previously reported methods in gram scale [34] .…”

Section: Resultsmentioning

confidence: 99%

“…The use of cyanamides as starting material for the preparation of guanidines is a well stablished methodology. [33] Thus, in order to synthesize compounds 3 a-g we obtained the pyrimidinebearing cyanamide 5 following previously reported methods in gram scale. [34] With cyanamide 5 in hand, it was coupled with the corresponding amines (as hydrochlorides) to give the desired N,N'-disubstituted guanidines with yields ranging from 50 to 75 % (Scheme 1A).…”

Section: Chemistrymentioning

confidence: 99%

Development of an Improved Guanidine‐Based Rac1 Inhibitor with in vivo Activity against Non‐Small Cell Lung Cancer

et al. 2021

View full text Add to dashboard Cite

The Rho GTPase Rac1 is involved in the control of cytoskeleton reorganization and other fundamental cellular functions. Aberrant activity of Rac1 and its regulators is common in human cancer. In particular, deregulated expression/activity of Rac GEFs, responsible for Rac1 activation, has been associated to a metastatic phenotype and drug resistance. Thus, the development of novel Rac1‐GEF interaction inhibitors is a promising strategy for finding new preclinical candidates. Here, we studied structure–activity relationships within a new family of N,N’‐disubstituted guanidine as Rac1 inhibitors. We found that compound 1D‐142, presents superior antiproliferative activity in human cancer cell lines and higher potency as Rac1‐GEF interaction inhibitor in vitro than parental compounds. In addition, 1D‐142 reduces Rac1‐mediated TNFα‐induced NF‐κB nuclear translocation during cell proliferation and migration in NSCLC. Notably, 1D‐142 allowed us to show for the first time the application of a Rac1 inhibitor in a lung cancer animal model.

show abstract

Recent developments in guanylating agents

Cited by 143 publications

References 28 publications

On Guanidinium and Cellular Uptake

On Guanidinium and Cellular Uptake

Cyanobiphenyl versus Alkoxybiphenyl: Which Mesogenic Unit Governs the Mesomorphic Properties of Guanidinium Ionic Liquid Crystals?

Development of an Improved Guanidine‐Based Rac1 Inhibitor with in vivo Activity against Non‐Small Cell Lung Cancer

Contact Info

Product

Resources

About