Synthese von 1.3.5‐Triazinen

Eilingsfeld, Heinz; Scheuermann, H.

doi:10.1002/cber.19671000614

Cited by 16 publications

(11 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S-Methyl-guanylisothiouronium iodide was prepared as previously described (11). Briefly, iodomethane (Acros) was added dropwise to a suspension of 2-imino-4-thiobiuret (Aldrich) in 100% ethanol while stirring at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Novel Compounds Containing Multiple Guanide Groups That Bind the HIV Coreceptor CXCR4

Wilkinson

Pincus

Shepard

et al. 2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The G-protein-coupled receptor CXCR4 acts as a coreceptor for human immunodeficiency virus type 1 (HIV-1) infection, as well as being involved in signaling cell migration and proliferation. Compounds that block CXCR4 interactions have potential uses as HIV entry inhibitors to complement drugs such as maraviroc that block the alternate coreceptor CCR5 or in cancer therapy. The peptide T140, which contains five arginine residues, is the most potent antagonist of CXCR4 developed to date. In a search for nonpeptide CXCR4 ligands that could inhibit HIV entry, three series of compounds were synthesized from 12 linear and branched polyamines with 2, 3, 4, 6, or 8 amino groups, which were substituted to produce the corresponding guanidines, biguanides, or phenylguanides. The resulting compounds were tested for their ability to compete with T140 for binding to the human CXCR4 receptor expressed on mammalian cells. The most effective compounds bound CXCR4 with a 50% inhibitory concentration of 200 nM, and all of the compounds had very low cytotoxicity. Two series of compounds were then tested for their ability to inhibit the infection of TZM-bl cells with X4 and R5 strains of HIV-1. Spermine phenylguanide and spermidine phenylguanide inhibited infection by X4 strains, but not by R5 strains, at low micromolar concentrations. These results support further investigation and development of these compounds as HIV entry inhibitors.

show abstract

Section: Methodsmentioning

confidence: 99%

Novel Compounds Containing Multiple Guanide Groups That Bind the HIV Coreceptor CXCR4

Wilkinson

Pincus

Shepard

et al. 2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…18 S-methyl derivative 1b was prepared from 2-imino-4-thiobiuret and methyl iodide in 91% yield. 19 Phenolic derivate 1d was obtained from cyanoguanidine dihydrochloride in phenol as solvent at 70 °C for 3 hours in 33% yield. 20 Finally, N-guanyl-O-methylisourea hydroacetate (1f) was synthesized in two steps from cyanoguanidine in methanol under reflux for 2 hours in the presence of copper acetate monohydrate, then the product was released from the copper complex following hydrogen sulphide treatment, with a 46% overall yield.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: 2mentioning

confidence: 99%

“…As described. 19 Briefly, iodomethane was added dropwise to a suspension of 2-imino-4-thiobiuret (Aldrich) in 100% ethanol while stirring at r.t. The reaction flask was shaken at 37 °C for 2 h. The solvent was removed by evaporation, and the residue was washed with cold diethyl ether to give a solid, which was collected by filtration and used without further purification.…”

Section: S-methyl-guanylisothiouronium Iodide (1b)mentioning

confidence: 99%

See 1 more Smart Citation

Mild Biamidine-Transfer Conditions for the Synthesis of Aliphatic Biguanides

Bardovskyi

Fabre

Ronco

et al. 2021

SynOpen

View full text Add to dashboard Cite

This study focuses on the development of new synthetic pathways to monosubstituted biguanides from amines. An exhaustive comparison of the conditions and reagents used for biamidine transfer was performed. New reagents were synthesized and optimized conditions for the synthesis of substituted biguanides under mild conditions were developed. Eventually, two high-yielding and straightforward protocols for the transfer of a biamidine group to various amines are proposed and their scope and limitations have been explored. These conditions include: i) a direct chromatography-free procedure and ii) an eco-friendly procedure in water compatible with bioinspired molecules. They are particularly efficient for the demanding conversion of aliphatic amines.

show abstract

“…Biguanidine and oxamidine analogues related to 1 and 2 were prepared and are shown in Table . The biguanide transfer reagent 90 (eq 4) was prepared by alkylation of iminothiobiuret with methyl iodide . This compound was then condensed with glycine, β-alanine, 3-aminopropionic acid, and taurine to give the desired biguanide analogues 33 − 36 .…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Biological Activity of Aminoguanidine and Diaminoguanidine Analogues of the Antidiabetic/Antiobesity Agent 3-Guanidinopropionic Acid

Vaillancourt¹,

Larsen

Tanis

et al. 2001

J. Med. Chem.

View full text Add to dashboard Cite

3-Guanidinopropionic acid (1) has been demonstrated both to improve insulin sensitivity and to promote weight loss selectively from adipose tissue in animal models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has also been shown to be a substrate for both the creatine transporter and creatine kinase, leading to marked accumulation in muscle tissue as the corresponding N-phosphate. The corresponding aminoguanidine analogue 2 was recently discovered to retain the antidiabetic activity of 1 while being markedly less susceptible to creatine-like metabolism, suggesting that it should have less potential to accumulate in muscle. Further structural modification of 2 was undertaken to investigate whether the antidiabetic potency could be augmented while maintaining resistance to creatine-like metabolism. Modifications such as alpha-alkylation, homologation, and bioisosteric replacement of the aminoguanidine all were detrimental to antidiabetic activity. However, the simple regioisomeric aminoguanidinoacetic acid 9 and diaminoguanidinoacetic acid analogue 7 were found to be equipotent to 2, leading eventually to the discovery of the significantly more potent diaminoguanidinoacetic acid regioisomers 52 and 53. Further attempts to modify the more active template represented by 52 led only to reductions in antidiabetic activity. Each of the new active analogues displayed the same resistance to creatine-like metabolism as 2. Further testing of 7, 9, and 53 in obese diabetic ob/ob mice confirmed that weight loss is induced selectively from adipose tissue, similar to the lead 1. Administration of 53 to insulin-resistant rhesus monkeys led to reductions in both fasting and post-prandial plasma glucose levels with concomitant reductions in plasma insulin levels, suggesting that the compound improved the action of endogenous insulin. Compounds 7 and 53 were selected for further preclinical development.

show abstract

Synthese von 1.3.5‐Triazinen

Cited by 16 publications

References 8 publications

Novel Compounds Containing Multiple Guanide Groups That Bind the HIV Coreceptor CXCR4

Novel Compounds Containing Multiple Guanide Groups That Bind the HIV Coreceptor CXCR4

Mild Biamidine-Transfer Conditions for the Synthesis of Aliphatic Biguanides

Synthesis and Biological Activity of Aminoguanidine and Diaminoguanidine Analogues of the Antidiabetic/Antiobesity Agent 3-Guanidinopropionic Acid

Contact Info

Product

Resources

About