15763-12-9

Basic information

• Product Name: N-allyladenosine
• Synonyms: N-allyladenosine
• CAS NO: 15763-12-9
• Molecular Formula: C13H17N5O4
• Molecular Weight: 307.31
• Mol File: 15763-12-9.mol

Chemical Properties

• Melting Point: 165-167 °C
• Boiling Point: 646.2°Cat760mmHg
• Flash Point: 344.6°C
• Appearance: /
• Density: 1.67g/cm³
• Vapor Pressure: 1.4E-17mmHg at 25°C
• Refractive Index: 1.749
• PKA: 13.12±0.70(Predicted)
• CAS DataBase Reference: N-allyladenosine(CAS DataBase Reference)
• NIST Chemistry Reference: N-allyladenosine(15763-12-9)
• EPA Substance Registry System: N-allyladenosine(15763-12-9)

Safety Data

• Hazardous Substances Data: 15763-12-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
N-Allyladenosine is used as an anti-angiogenic agent for targeting human microvascular endothelial cells in vitro. Its ability to inhibit angiogenesis makes it a potential candidate for the development of treatments aimed at preventing the growth and spread of cancerous tumors, which often rely on the formation of new blood vessels for nourishment and expansion.

InChI:InChI=1/C13H17N5O4/c1-2-3-14-11-8-12(16-5-15-11)18(6-17-8)13-10(21)9(20)7(4-19)22-13/h2,5-7,9-10,13,19-21H,1,3-4H2,(H,14,15,16)

Upstream product

• 1055040-20-4 6-N-allyl-2',3',5'-tris-O-(tert-butyldimethylsilyl)-6-N-(2-trimethylsilylethoxycarbonyl)adenosine 
• 2004-06-0 6-Chloropurine riboside 
• 107-11-9 1-amino-2-propene 
• 7387-58-8 6-N-2',3',5'-tri-O-tetraacetyladenosine 
• 5987-73-5 2',3',5'-O-triacetyl-6-chloroinosine 
• 3181-38-2 2',3',5'-tri-O-acetylinosine 
• 58-63-9 Inosine 
• 1001067-26-0 2',3',5'-tris-O-(tert-butyldimethylsilyl)-6-N-(2-trimethylsilylethoxycarbonyl)adenosine 

Downstream Products

• 5446-37-7 N⁶-allyladenine 

Relevant articles and documents

Some short-chain N6-substituted adenosine analogues with antitumor properties.

The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a number of in vitro and in vivo tumor cell systems. Very good increases in life spans of mice bearing mammary carcinoma were obtained by treatment with the N6-allyl, N6-isopropyl, and N6-propargyl analogues, respectively. In rats, the N6-allyl analogue slowed the rate of transplantable mammary tumor growth by one-fourth. The short-chain adenosine analogues are more active in the treatment of animal carcinomas than in the leukemia or sarcoma tumor cell systems.

Chemical modification of the plant isoprenoid cytokinin N 6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication

In this study, we demonstrate that N6-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 ± 0.2 ?1/4M and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N6-position did not result in a lower EC50 value. However, in particular with the synthesis of N6-(5-hexene-2-yne-1-yl)adenosine (EC50 Combining double low line 4.3 ± 1.5 ?1/4M), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI > 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71.

N6-Alkyladenosines: Synthesis and evaluation of in vitro anticancer activity

A series of adenosine analogues differently substituted in N 6-position were synthesized to continue our studies on the relationships between structure and biological activity of iPA. The structures of the compounds were confirmed by standard studies of 1H NMR, MS and elemental analysis. These molecules were then evaluated for their anti-proliferative activity on bladder cancer cells. We found that some of these compounds possess anti-proliferative activity but have no effect on cell invasion and metalloprotease activity.

N6-isopentenyladenosine a new potential anti-angiogenic compound that targets human microvascular endothelial cells in vitro

N6-isopentenyladenosine is an anti-proliferative and pro-apoptotic atypical nucleoside for normal and tumor cells. Considering the role of angiogenesis in various diseases, we investigated the cytotoxic effect of N6-isopentenyladenosine on human microvascular endothelial cells, protagonists in angiogenesis. Our results show that N6-isopentenyladenosine induced a significant reduction of cell viability, upregulated p21 and promoted caspase-3 cleavage in a dose dependent manner leading to apoptotic cell death as detected by FACS analysis. To understand structure-function relationship of N6-isopentenyladenosine, we investigated the effect of some N6-isopentenyladenosine analogs. Our results suggest that N6-isopentenyladenosine and some of its derivatives are potentially novel angiostatic agents and might be associated with other anti-angiogenic compounds for a better outcome.

Chemical modification of the plant isoprenoid cytokinin N6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication

In this study, we demonstrate that N6-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 ± 0.2 mM and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N6-position did not result in a lower EC50 value. However, in particular with the synthesis of N6-(5-hexene-2-yne-1-yl)adenosine (EC50 = 4.3 ± 1.5 mM), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71.

Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L

Histone3-lysine79 (H3K79) methyltransferase DOT1L has been found to be a drug target for acute leukemia with MLL (mixed lineage leukemia) gene translocations. A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with Ki values as low as 0.5 nM. These compounds also show high selectivity (>4500-fold) over three other histone methyltransferases. Structure-activity relationships (SAR) of these compounds for their inhibitory activities against DOT1L are discussed. Potent DOT1L inhibitors exhibit selective activity against the proliferation of MLL-translocated leukemia cell lines MV4;11 and THP1 with EC50 values of 4-11 μM. Isothermal titration calorimetry studies showed that two representative inhibitors bind with a high affinity to the DOT1L:nucleosome complex and only compete with the enzyme cofactor SAM (S-adenosyl-l-methionine) but not the substrate nucleosome.

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.

Adenosine analogues as inhibitors of Trypanosoma brucei phosphoglycerate kinase: Elucidation of a novel binding mode for a 2-Amino-N6-substituted adenosine

As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N6-, 2-amino-N6-, and N2-substituted adenosine analogues were synthesized and tested to establish structure - activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for N6-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N6-[2-(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC50 of 130 μM. 2-[[2-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC50 of 500 μM. To explore the potential of an additive effect that having the N6 and N2 substitutions in one molecule might provide, the best ligands from the two series were incorporated into N6,N2-disubstituted adenosine analogues to yield N6-(2-phenylethyl)-2-[(2-phenylethyl)amino]adenosine (69) as a 30 μM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 A? X-ray structure of a T. brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this 'flipped and rotated' binding mode.

Alkylation of 6-N-acylated adenosine derivatives by the use of phase transfer catalysis

6-N- or N1-Alkylation of 6-N-acyl adenosine derivatives with alkyl halides in CH2Cl2 - 1 mol dm-3 NaOH in the presence of Bu4NBr has been studied.A variety of N-acyl groups have been examined.Consequently, the use of the acetyl and 2-(trimethylsilyl)ethoxycarbonyl groups resulted in the corresponding 6-N-alkylated products in high yields.It was also found that, when the benzoyl group was chosen as the N-acyl group, N1-alkylated products were obtained along with 6-N-alkylated products were obtained along with 6-N-alkylated products.The structure of the 6-N- and N1-alkylated adenosine derivatives has been determined by 1H and 13C NMR spectroscopy.