56934-06-6

Basic information

• Product Name: Adenosine, N-(6-aminohexyl)-
• CAS NO: 56934-06-6
• Molecular Formula: C16H26N6O4
• Molecular Weight: 366.42
• Mol File: 56934-06-6.mol

Chemical Properties

• CAS DataBase Reference: Adenosine, N-(6-aminohexyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: Adenosine, N-(6-aminohexyl)-(56934-06-6)
• EPA Substance Registry System: Adenosine, N-(6-aminohexyl)-(56934-06-6)

Safety Data

• Hazardous Substances Data: 56934-06-6(Hazardous Substances Data)

Upstream product

• 124-09-4 1,6-Hexanediamine 
• 58-63-9 Inosine 
• 2004-06-0 6-Chloropurine riboside 

Relevant articles and documents

A Structure-Activity Relationship Study of Bitopic N 6-Substituted Adenosine Derivatives as Biased Adenosine A1 Receptor Agonists

The adenosine A1 receptor (A1AR) is a potential novel therapeutic target for myocardial ischemia-reperfusion injury. However, to date, clinical translation of prototypical A1AR agonists has been hindered due to dose limiting adverse effects. Recently, we demonstrated that the biased bitopic agonist 1, consisting of an adenosine pharmacophore linked to an allosteric moiety, could stimulate cardioprotective A1AR signaling in the absence of unwanted bradycardia. Therefore, this study aimed to investigate the structure-activity relationship of compound 1 biased agonism. A series of novel derivatives of 1 were synthesized and pharmacologically profiled. Modifications were made to the orthosteric adenosine pharmacophore, linker, and allosteric 2-amino-3-benzoylthiophene pharmacophore to probe the structure-activity relationships, particularly in terms of biased signaling, as well as A1AR activity and subtype selectivity. Collectively, our findings demonstrate that the allosteric moiety, particularly the 4-(trifluoromethyl)phenyl substituent of the thiophene scaffold, is important in conferring bitopic ligand bias at the A1AR.

An improved synthesis of N6-(6-aminohexyl)FAD

We report an improved synthesis of N6-(6-aminohexyl)FAD (1) using an efficient one-pot conversion of inosine to the N-trifluoroacetyl protected N6-(6-aminohexyl)adenosine 3. The 5'-O-phosphorylated AMP derivative 4, activated as the imidazolide, was coupled with commercial sodium riboflavin phosphate by using 18-crown-6 in DMF.

Synthesis and pharmacological evaluation of modified adenosines joined to mono-functional platinum moieties

The synthesis of four novel platinum complexes, bearing N6-(6- Aminohexyl) adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of monofunctional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation.

Effect of linker length and composition on heterobivalent ligand-mediated receptor cross-talk between the A1 adenosine and β2 adrenergic receptors

Heterobivalent ligands that possess pharmacophores designed to interact with both the A1 adenosine receptor (A1AR) and the β2 adrenergic receptor (β2AR) were prepared. More specifically, these ligands contain an adenosine moiety that is linked via its N6-position to the amino group of the saligenin-substituted ethanolamine moiety present in the well-known β2AR agonist, salbutamol. The affinities of these ligands were determined at both receptors and found to vary with linker length and composition. With all compounds, affinity and functional potencies were found to have selectivity for the A 1AR over the β2AR. In all cases, cAMP accumulation (a β2AR-mediated response) was mainly observed when the A 1AR was blocked or its function decreased by pertussis toxin or chronic agonist treatment. This suggests that heterobivalent compounds for receptors that mediate opposite responses might be useful for elucidating the mechanisms of receptor cross-talk and how this interaction, in terms of responsiveness, may change under pathophysiological conditions. A molecular double date: Heterobivalent ligands containing pharmacophores designed to interact with both the A1 adenosine receptor (A1AR) and the β2 adrenergic receptor (β2AR) were prepared. The affinity and potency of these ligands at both receptors were found to be dependent upon the linker length and composition. The data suggest that heterobivalent ligands for receptors mediating opposite responses might be useful for investigating the regulation of receptor cross-talk in health and disease. Copyright

Fluorescence-Lifetime-Sensitive Probes for Monitoring ATP Cleavage

Adenosine triphosphate (ATP) probes modified with fluorescence dyes that change their fluorescence properties upon cleavage are an interesting tool for monitoring enzymatic ATP turnover. As a readout parameter, fluorescence lifetime is attractive because it is nearly independent of concentration. In our study, we synthesised and investigated fifteen different ATP analogues, in which the fluorophores were attached to the γ-phosphate of ATP. All analogues showed distinctly different fluorescence lifetimes compared to the corresponding values of the free fluorophores. Both increases and decreases in fluorescence lifetime were observed upon attachment to ATP. To shed light on the photophysical processes governing the lifetime changes, we performed photoelectron spectroscopy in air (PESA) to determine HOMO energy levels and time-resolved fluorescence spectroscopy to obtain rate constants. We present evidence that fluorescence quenching in the compounds tested is dynamic and attributed to photoinduced electron transfer (PET), whereas fluorescence lifetime increases are caused by stacking interactions between chromophore and the nucleobase reducing non-radiative relaxation. Finally, we demonstrate that enzymatic cleavage of the ATP analogues presented can be followed by continuous monitoring of fluorescence lifetime changes.

Novel Irreversible Agonists Acting at the A1 Adenosine Receptor

The A1 adenosine receptor (A1AR) is an important G protein-coupled receptor that regulates a range of physiological functions. Herein we report the discovery of novel irreversible agonists acting at the A1AR, which have the potential to serve as useful research tools for studying receptor structure and function. A series of novel adenosine derivatives bearing electrophilic substituents was synthesized, and four compounds, 8b, 15a, 15b, and 15d, were shown to possess similar potency and efficacy to the reference high efficacy agonist, NECA, in an assay of ERK1/2 phosphorylation assay. Insensitivity to antagonist addition in a real-time, label-free, xCELLigence assay was subsequently used to identify compounds that likely mediated their agonism through an irreversible interaction with the A1AR. Of these compounds, 15b and 15d were more directly validated as irreversible agonists of the A1AR using membrane-based [3H]DPCPX and [35S]GTPγS binding experiments.

New conjugates of mycophenolic acid and their antiproliferative activity

The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of N6-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds 4a–h were evaluated on leukemia cell line (Jurkat) and PBMC from healthy donors. Length of the linker influenced observed activity. The compound 4b possessing 1,3-diamine spacer exhibited the most promising results and can be considered to further investigations.

Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family

Adenine derivatives bearing substituents in the 2-, N6-, 7-, 8-, and/or 9-position and a series of deazapurines were synthesized and investigated in [3H]adenine binding studies at the adenine receptor in rat brain cortical membrane preparations (rAde1R). Steep structure-activity relationships were observed. Substitution in the 8-position (amino, dimethylamino, piperidinyl, piperazinyl) or in the 9-position (2-morpholinoethyl) with basic residues or introduction of polar substituents at the 6-amino function (hydroxy, amino, acetyl) represented the best modifications. Functional evaluation of selected adenine derivatives in adenylate cyclase assays at 1321N1 astrocytoma cells stably expressing the rAde1R showed that all compounds investigated were agonists or partial agonists. A subset of compounds was additionally investigated in binding studies at human embryonic kidney (HEK293) cells, which also express a high-affinity adenine binding site. Structure-affinity relationships at the human cell line were similar to those at the rAde1R, but not identical. In particular, N 6-acetyladenine (25, Ki rat: 2.85 μM; Ki human: 0.515 μM) and 8-aminoadenine (33, Ki rat: 6.51 μM; Ki human: 0.0341 μM) were much more potent at the human as compared to the rat binding site. The new AdeR ligands may serve as lead structures and contribute to the elucidation of the functions of the adenine receptor family. 2009 American Chemical Society.

Dual acting antioxidant A1 adenosine receptor agonists

Herein we report the synthesis and biological evaluation of some potent and selective A1 adenosine receptor agonists, which incorporate a functionalised linker attached to an antioxidant moiety. N6-(2,2,5,5-Tetramethylpyrrolidin-1-yl

Anti-HCV nucleoside derivatives

The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.