443-72-1

Usage

Uses

Used in Pharmaceutical Industry:
6-(METHYLAMINO)PURINE is used as a reagent for substitution of adenine nucleotide analogs containing a bicyclohexane ring system locked in the northern conformation. This substitution enhances the potency of py receptor antagonists, making it a valuable tool in the development of new drugs.
Used in Epigenetic Research:
6-(METHYLAMINO)PURINE is used as an epigenetic mark in single-celled organisms and is also rarely observed in mammalian cells. Studying its role in epigenetic regulation can provide insights into the mechanisms of gene expression and regulation, which can be applied to various fields such as genetics, molecular biology, and medicine.

Purification Methods

The purine is best purified by recrystallising 2g from 50mL of H2O and 1.2g of charcoal. [UV: Albert & Brown J Chem Soc 2060 1954; UV: Mason J Chem Soc 2071 1954; see also Elion et al. J Am Chem Soc 74 411 1952.] The picrate has m 265o(257o) [Bredereck et al. Chem Ber 81 307 1948]. [Beilstein 26 III/IV 3565.]

InChI:InChI=1/C6H7N5/c1-7-5-4-6(10-2-8-4)11-3-9-5/h2-4H,1H3,(H,7,8,9,10,11)

Upstream product

• 1006-22-0 1-methyl-1,7⁽⁹⁾-dihydro-purine-6-thione 
• 74-89-5 methylamine 
• 50-66-8 6-(methylthio)-1H-purine 
• 50-44-2 6H-purine-6-thione 
• 5142-22-3 1-methyladenine 
• 1867-73-8 N⁶-methyladenosine 
• 111098-24-9 Benzotriazol-1-ylmethyl-(9H-purin-6-yl)-amine 
• 5404-86-4 6-hydrazinyl-7H-purine 
• 83366-42-1 4,6-bis(methylamino)-5-phenylazopyrimidine 
• 2002-35-9 N-6-methyl-2'-deoxyribofuranosil adenine 
• 593-51-1 methylamine hydrochloride 
• 87-42-3 6-chloropurine 
• 87-42-3 6-chloro-1H-purine 
• 87-42-3 6-chloro-7H-purine 

Downstream Products

• 21928-82-5 methyl-nitroso-(7(9)H-purin-6-yl)-amine 
• 1867-73-8 N⁶-methyladenosine 
• 70091-21-3 9-(2-chloro-6-fluorobenzyl)-6-methylaminopurine 
• 81060-73-3 methyl-(9-benzyl-9H-purin-6-yl)amine 
• 129918-40-7 3-benzyl-6-(methylamino)purine 
• 70091-25-7 N-methyl-9-(2,6-dichlorobenzyl)adenine 
• 125486-32-0 N-methyl-N,9-bis(2,6-dichlorobenzyl)adenine 
• 125486-34-2 (2,6-Dichloro-benzyl)-[3-(2,6-dichloro-benzyl)-3H-purin-6-yl]-methyl-amine 
• 101155-02-6 BW-A 78U 
• 142544-63-6 3'-(6-methylaminopurin-9-yl)-3'-deoxy-1',5',6'-tri-O-(methanesulfonyl)-muco-inositol 
• 32865-83-1 9-trimethylsilyl-6-methylaminopurine 
• 71118-16-6 N⁶-methyl-2',3',5'-tri-O-benzoyladenosine 
• 2009-52-1 N₆,N₉-dimethyladenine 
• 49581-45-5 methyl-(3-methyl-3H-purin-6-yl)-amine 

Relevant academic research and scientific papers

Purines. LXI. An attempted synthesis of 2'-deoxy-7-methyladenosine: Glycosidic hydrolyses of the N6-methoxy derivative and 2'-deoxy-N(x)- methyladenosines

In an attempt to synthesize 2'-deoxy-7-methyladenosine (5b), 2'-deoxy- N6-methoxyadenosine (13b) was treated with MeI in AcNMe2 at 0°C for 7h to give the 2'-deoxy-N6-methoxy-7-methyladenosine salt (14b), which was unstable and easily underwent glycosidic hydrolysis in H2O at 16-18°C to form N6-methoxy-7-methyladenine (15). On account of such instability, hydrogenolysis of 14b in H2O using hydrogen and Raney Ni catalyst failed to afford the desired nucleoside (5b). 2'-Deoxy-N6-methyladenosine (2b), 2'- deoxy-1-methyladenosine (3b), and 14b were found to undergo glycosidic hydrolysis in 0.1 N aqueous HCl at 25°C at rates of 7.92 x 10-2 min-1 (half-life 87.5 min), 5.02 x 10-3min-1 (half-life 138 min), and 2.31 x 10-2 min-1 (half-life 30.0 min), respectively, while the rate in the case of 5h was roughly estimated to be ca. 2 min-1 (half-life 0.35 min).

Method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK)

The present invention relates to a method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK) and the use of the compounds in the prevention or treatment of disease, including pre-diabetes, type 2 diabetes, syndrome X, metabolic syndrome and obesity.

HETEROARYLPHENYLUREA DERIVATIVE

The present invention provides a compound represented by the formula (1): wherein R 1 , R 2 and R 5 are each independently selected from a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl is substituted with a halogen atom and the like; R 3 and R 4 are each independently selected from a hydrogen atom, a halogen atom, a substituted C 1 -C 6 alkyl group and the like; R 6 and R 7 are each independently selected from a hydrogen atom and a halogen atom; Z 1 and Z 2 are each independently selected from a hydrogen atom, a hydroxyl group and -O(CHR 11 )OC(=O)R 12 ; Q is a group of the formula: (wherein G 1 is C-Y 2 or N; a ring A is a benzene ring or a 5- to 6-membered unsaturated heterocycle) a pharmaceutically acceptable salt thereof or a prodrug thereof.

PHOSPHODIESTERASE INHIBITORS

The present invention relates to purine derivatives, which can be used as selective phosphodiesterase (PDE) type IV inhibitors. Compounds disclosed herein can be useful in the treatment of asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases especially in humans. Also provided are processes for the preparation of disclosed compounds, pharmaceutical composition containing the disclosed compounds and their use as selective phosphodiesterase (PDE) type IV inhibitors.

Design, synthesis and structure-activity relationships of a series of 9-substituted adenine derivatives as selective phosphodiesterase type-4 inhibitors

Adenine derivatives substituted in position 9 have been demonstrated to have potent cyclic nucleotide phosphodiesterase (PDE) inhibition properties with high selectivity toward PDE-4. Starting from our initial lead compound 9-(2-fluorobenzyl)-N6-methyl-2-trifluoromethyladenine (4, NCS613), we designed and synthesized a new series of 9-substituted derivatives for developing structure-activity relationship studies. This new series of derivatives showed increased potencies and better selectivity profiles. Structural modifications were achieved in parallel on three different positions of the adenine ring, and led to the following observations: (i) introduction of a lipophilic substituent such as trifluoromethyl, n-propyl group or iodine in the C-2 position is favourable for both the PDE-4 inhibitory activity and the selectivity towards other isoenzymes; (ii) functionalization of the N9 benzyl group with a 2-methoxy substituent led to remarkably more active compounds; (iii) replacement of the N6-methylamino moiety by other amino groups is detrimental to the activity. Among all derivatives prepared, the 9-(2-methoxybenzyl)-N6-methyl-2-trifluoromethyladenine (9r), 9-(2-methoxybenzyl)-N6-methyl-2-n-propyladenine (9s), and the 2-iodo-9-(2-methoxybenzyl)-N6-methyladenine (13b) were found to be the most potent inhibitors within this series (PDE-4-IC50=1.4, 7.0, and 0.096 nM, respectively). Compared to our reference compound 4, which showed an IC50 of 42 nM, the derivative 13b was found 450-fold more potent. Moreover, 2-iodo-9-(2-methoxybenzyl)-N6-methyladenine (13b) and 9-(2-methoxybenzyl)-N6-methyl-2-trifluoromethyladenine (9r), were at least 50 000-150 000 times more selective for the PDE-4 than for the other PDE families. Additionally, these new derivatives showed improved efficiency in inhibiting the TNFα release from mononuclear cells from healthy subjects (e.g. adenines 7l, 9s and 13b). Thus, compounds 7l, 9r, 9s and 13b are among the most potent and selective PDE-4 inhibitors reported so far and represent very promising pharmacological tools for a better understanding of the signal transduction involving cyclic AMP within the cell: this pathway is implicated in the physiology and the pathophysiology of inflammation, asthma and autoimmune disorders.

Purines. LXXII. Oxidation of N6-alkyladenines with m-chloroperoxybenzoic acid leading to N6-alkyladenine 1-oxides

Oxidations of N6-methyladenine (8a) and N6-benzyladenine (8b) with m- chloroperoxybenzoic acid (mcpba) in methanol have been found to afford the N(1)-oxides 7a,b in 36% and 35% yields, respectively. The structure of 7b has been established by leading it to N6-methoxyadenine (10) through O- methylation, Dimroth rearrangement, and nonreductive debenzylation. On the other hand, N6,N6-dimethyladenine (16) afforded the N(3)-oxide 17 in 40% yield on treatment with Mcpba in methanol. On the basis of these findings, together with data accumulated for N-oxidations of adenine, N(x)- monosubstituted adenines, and 6-substituted purines, the formation of hydrogen bonding between the 6-amino Nh and the carbonyl oxygen of a peroxycarboxylic acid may account for regioselective N(1)and N(7)-oxidations of adenine and N(x)-monosubstituted adenines.

Process for preparing N6,9-disubstituted adenine

A process for preparing N6, 9-disubstituted adenines which comprises reacting a metal salt of N6 -substituted adenine with a benzyl halide compound, preferably in the presence of a phase transfer catalyst. According to the process, the N6,9-disubstuted adenines can be obtained in high yields and good selectivity.

A 15N-STUDY ON THE DEAMINATION OF 1-AMINOPURINIUM SALTS WITH AMINES

Reaction of 1-aminoadenosinium mesitylenesulphonate, 1a, with methanolic ammonia for 10 h at 80 deg C yields adenosine, 7a, and nebularine, 6a.With methanolic methylamine 1a gives 6-methylamino-9-β-D-ribofuranosylpurine, 8a, and adenosine, 7a, respectively.Similar results are obtained with the salt of 1-amino-2',3'-O-isopropylideneadenosine, 1b. 1-Aminoadeninium mesitylenesulphonate, 1c, with methanolic methylamine only yields 6-(methylamino)purine, 8c.In contrast, the mesitylenesulphonate salt of 1,2-diaminopurine, 11, with methanolic methylamine gives only deamination at N1, affording 2-aminopurine, 12.Studies with 15N-labelled methanolic ammonia or 15N-labelled purinium compounds show that in all these reactions, except that of 11, a ring-opening mechanism (ANRORC-mechanism) is involved.

The Chemistry of N-Substituted Benzotriazoles. Part 4. A Novel and Versatile Method for the Mono-N-alkylation of Aromatic and Heteroaromatic Amines

Mono-N-alkylation of aromatic and heteroaromatic amines is achieved in high yield by NaBH4 reduction of the adducts formed from benzotriazole, aliphatic aldehydes and the amines.Reaction of the same adducts with Grignard reagents gives N-(secondary alkyl)arylamines.Carboxy groups need no protection and nitro groups are unaffected.Adenine is mono-N-alkylated in high yield.