5440-16-4

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 35, p. 3981, 1970 DOI: 10.1021/jo00836a096

InChI:InChI=1/C13H13N5/c1-18-9-17-11-12(15-8-16-13(11)18)14-7-10-5-3-2-4-6-10/h2-6,8-9H,7H2,1H3,(H,14,15,16)

Upstream product

• 2346-74-9 6-chloro-9-methyl-9H-purine 
• 100-46-9 benzylamine 
• 128730-40-5 N⁶-benzyl-N⁶-methoxy-9-methyladenine hydrobromide 
• 87-42-3 6-chloropurine 
• 74-88-4 methyl iodide 
• 13300-29-3 N⁶-methoxy-9-methyladenine 
• 100-39-0 benzyl bromide 
• 1214-39-7 6-benzyladenine 

Relevant academic research and scientific papers

Molecular and crystal structures of dialkylated adenines (N6,N9-Me2Ade, N3,N6-MeBnAde) and cytosines (N1,N4-Me2Cyt)

N6,N9-Dimethyladenine (N6,N9-Me2Ade, 1) and N1,N4-dimethylcytosine (N1,N4-Me2Cyt, 3) were obtained by conventional methods, whereas the reaction of N6-benzyladenine with MeI/NaOH resulted in the formation of N3,N6-MeBnAde (2a) and N6,N9-BnMeAde (2b). All compounds were fully characterized by microanalysis, NMR spectroscopy (1H, 13C) and 1, 2a·2MeOH and 3 also by single-crystal X-ray diffraction analyses. In single-crystals of 1, obtained from THF solutions, twofold N6-H···N7′ hydrogen-bonded dimeric units (N6,N9-Me2Ade)2 (AA12 type according to Jeffrey and Saenger, 1991) were found. This proved to be another modification than that obtained by crystallization N6,N9-Me2Ade from MeOH/PhCl (Sternglanz, 1978). Crystals of 2a·2MeOH exhibited an analogous hydrogen bond pattern as found in 1. The shorter N6···N7′ distance in 2a·2MeOH (2.932(2) A?) indicates slightly stronger hydrogen bonds than in 1 (3.078(3) A?). Crystals of 3 are built up from centrosymmetric dimers (N1,N4-Me2Cyt)2 having a twofold N4-H···N3′ hydrogen bond, thus exhibiting the CC32 hydrogen bond pattern. The hydrogen bonding patterns in the dialkylated nucleobase derivatives are discussed in terms of those found in crystals of the less substituted nucleobases N9-MeAde and Cyt/N1-MeCyt, respectively.

Cytokinin-derived cyclin-dependent kinase inhibitors: Synthesis and cdc2 inhibitory activity of olomoucine and related compounds

Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of edk inhibition showed that the 1, 3, and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)2(R)-[[1-(hydroxymethyl)propyl]amino]-9- isopropylpurine), and other N6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34(cdc2)/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G1/S and G2/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.

N6,9-Disubstituted Adenines: Potent, Selective Antagonists at the A1 Adenosine Receptor

N6-Substituted 9-methyladenines are potent antagonists of the activation of A1 adenosine receptors.The present study assessed the effect of N6 and N-9-substituents on the binding of adenines to the A1 and A2 receptors, respectively, of rat brain cortex and striatum and also on the antagonism of the A2 receptor mediated stimulation of the adenylate cyclase of PC12 cells by N-ethyladenosine-5'-uronamide.The potency ranking of 9-substituted adenines varied directly with the hydrophobicity of the substituent: cyclopentyl > phenyl > tetrahydrofuryl > ethyl > methyl > 2-hydroxyethyl.The 9-substituted adenines showed little selectivity for either receptor and the R enantiomer of N6-(1-phenyl-2-propyl)-9-methyladenine was only 4-fold more potent than the S enantiomer at the A1 receptor.An N6-cyclopentyl substituent increased potency at the A1 receptor and decreased potency at the A2 receptor, resulting in selectivity for the A1 receptor of up to 39-fold.The N6-cyclopentyl group completely overshadowed the effect of the hydrophobicity of the 9-substituent.A 2-chloro substituent did not alter the potency of an N6-substituted 9-methyladenine.

Purines. xxxviii. A general synthesis of 7,9-dialkyladeninium salts from 9-alkyladenines by regioselective alkylation: Utilization of an N6-alkoxy group as a control synthon

A detailed account is given of the general synthetic route to 7,9-dialkyladeninium salts (16 18) from N6-alkoxy-9-alkyladenines (type 5 or 11--13), readily obtainable from 9-alkyladenines in three steps involving N(1)-oxidation, O-alkylation, a

COMPARISON OF CYTOKININ ACTIVITIES OF 9-SUBSTITUTED N6-BENZYLADENINES IN THE CUCUMIS AND AMARANTHUS BIOASSAYS

9-Substituted N6-benzyladenines were tested for their ability to eliminate the lag phase in and promote chlorophyll synthesis in Cucumis sativus cotyledons and for their effectiveness in eliciting the dark biosynthesis of betacyanin in Amaranthus tricolor cotyledon-hypocotyl explants.The following general relationships were established for dose-responses: (a) 9-ribosidation brought about little (in Amaranthus) or no (in Cucumis) decrease in activity relative to the free base, (b) the presence of a 9-ribose 5'-phosphate group moderately depressed activity in Amaranthus but slightly enhanced activity in Cucumis, (c) the presence of a 9-ribose 3',5'-cyclic phosphate group depressed activity substantially in both systems, more so in Amaranthus, (d) 9-glucosylation greatly decreased activity, as did 7-glucosylation, while 3-glucosylation depressed activity to a much lesser extent, in both systems, (e) 9-substitution with cyclopentyl, methyl, methoxymethyl, and tetrahydropyranyl groups reduced activity, the first two substituents more so than the last two, and (f) alteration of the 9-riboside group to a 9- moiety by oxidation-reduction led to complete (in Amaranthus) or nearly complete (in Cucumis) inactivation.Responses to hormone treatment were detectable after dark incubation times as short as 4 hr (in Cucumis) or 8 hr (in Amaranthus). - Key Word Index: Cucumis sativus; Cucurbitaceae; Amaranthus tricolor; Amaranthaceae; cytokinin activity; chlorophyll synthesis; amaranthin synthesis; bioassays; substituted N6-benzyladenines.