2846-96-0

Usage

Uses

Used in Pharmaceutical Industry:
6-morpholinopurine is used as an intermediate in the synthesis of antiviral and anticancer drugs due to its unique chemical structure and properties.
Used in Cardiovascular Applications:
6-morpholinopurine is used as a potential therapeutic agent for pulmonary hypertension and other cardiovascular diseases, as it acts as a potent inhibitor of cGMP-specific phosphodiesterase.
Used in Agricultural Applications:
6-morpholinopurine is used as a growth promoter and stress resistance enhancer in plants, contributing to improved agricultural productivity and crop resilience.

InChI:InChI=1/C9H11N5O/c1-3-15-4-2-14(1)9-7-8(11-5-10-7)12-6-13-9/h5-6H,1-4H2,(H,10,11,12,13)

Upstream product

• 24957-88-8 6-morpholino-5-nitropyrimidin-4-amine 
• 4010-79-1 2,8-dichloro-6-morpholin-4-yl-7⁽⁹⁾H-purine 
• 110-91-8 morpholine 
• 50-66-8 6-(methylthio)-1H-purine 
• 50-44-2 6H-purine-6-thione 
• 68-94-0 hypoxanthine 
• 87-42-3 6-chloropurine 
• 81693-59-6 5-amino-4-(cyanoformimidoyl)-1H-imidazole 
• 87-42-3 6-chloro-7H-purine 
• 5451-40-1 2,6-dichloro-7H-purine 
• 68-94-0 1,7-dihydro-6H-purin-6-one 
• 2562-52-9 2,6,8-trichloro-7H-purine 
• 4010-81-5 2-chloro-6-morpholin-4-yl-7⁽⁹⁾H-purine 

Relevant academic research and scientific papers

6-Morpholino- and 6-amino-9-sulfonylpurine derivatives. Synthesis, computational analysis, and biological activity

The synthesis of novel 6-chloro/morpholino/amino/-9-sulfonylpurine derivatives was accomplished in two ways, either (i) involving the condensation reaction of 6-chloropurine with commercially available arylsulfonyl chlorides in acetone and the presence of aqueous KOH at 0 °C, followed by the substitution of C6-chlorine with morpholine, or (ii) employing a reversed synthetic approach where 6-morpholinopurine and commercially available adenine bases were reacted with the corresponding alkyl, 2-arylethene and arylsulfonyl chlorides giving the N9 sulfonylated products, the latter particularly used where prior nonselective sulfonylation was observed. In both approaches, the sulfonylation reaction occurred regioselectively at the purine N9 position lacking any concurrent N7 derivatives, except in the case of a smaller methyl substituent on SO2 and the free amino group at C6 of the purine ring. The tautomeric features of initial N9 unsubstituted purines, as well as stability trends among the prepared N-9-sulfonylpurine derivates, were investigated using DFT calculations with an important conclusion that electron-donating C6 substituents are beneficial for the synthesis as they both promote the predominance of the desired N9 tautomers and help to assure the stability of the final products. The newly synthesized 6-morpholino and 6-amino-9-sulfonylpurine derivatives showed antiproliferative activity on human carcinoma, lymphoma, and leukemia cells. Among the tested compounds, 6-morpholino 17 and 6-amino 22 derivatives, with trans-β-styrenesulfonyl group attached at the N9 position of purine, proved to be the most effective antiproliferative agents, causing accumulation of leukemia cells in subG0 cell cycle phase.

Room-Temperature Amination of Chloroheteroarenes in Water by a Recyclable Copper(II)-Phosphaadamantanium Sulfonate System

Buchwald-Hartwig amination of chloroheteroarenes has been a challenging synthetic process, with very few protocols promoting this important transformation at ambient temperature. The current report discusses about an efficient copper-based catalytic system (Cu/PTABS) for the amination of chloroheteroarenes at ambient temperature in water as the sole reaction solvent, a combination that is first to be reported. A wide variety of chloroheteroarenes could be coupled efficiently with primary and secondary amines as well as selected amino acid esters under mild reaction conditions. Catalytic efficiency of the developed protocol also promotes late-stage functionalization of active pharmaceutical ingredients (APIs) such as antibiotics (floxacins) and anticancer drugs. The catalytic system also performs efficiently at a very low concentration of 0.0001 mol % (TON = 980,000) and can be recycled 12 times without any appreciable loss in activity. Theoretical calculations reveal that the π-acceptor ability of the ligand PTABS is the main reason for the appreciably high reactivity of the catalytic system. Preliminary characterization of the catalytic species in the reaction was carried out using UV-VIS and ESR spectroscopy, providing evidence for the Cu(II) oxidation state.

9-Sulfonyl-9(H)-Purine Derivatives Inhibit HCV Replication Via their Degradation Species

Cell-based screening of a privileged small molecule library led to the discovery of 9-sulfonyl-9(H)-purine as new scaffold for hepatitis C virus (HCV) inhibitors. Structure–activity relationship study with respect to the 2-, 6- and 9-positions in the purine core resulted in the identification of several active compounds with moderate potency against the HCV genotype 1b. Subsequent stability studies demonstrated that HCV inhibitors of this type were unstable in Dulbecco’s modified eagle medium (DMEM) and plasma, as well as glutathione-containing water, and their instability was closely related to their HCV inhibitory activity. A preliminary study of the mechanism of action showed that the sulfonamide bond at the 9-position of purine would be the primary degradation site and the resulting sulfonylation degradation species would mediate the anti-HCV activity of 9-sulfonyl-9(H)-purines. Results of this study demonstrated that 9-sulfonyl-9(H)-purine is an unstable scaffold for HCV inhibitors and further detailed analysis of the degradation species is needed to determine the main active components and direct target for this type of molecules.

Reactions of Adenine and Its N-Exo Substituted Analogues with Phenyl Glycidyl Ether

Abstract: The features of reactions of adenine with phenyl glycidyl ether depending on the solvent nature were studied. In DMF in the presence of K2CO3, an N9-alkyl derivative, an experimental antiviral drug 9-(2-hydroxy-3-phenoxypropyl)adenine, was formed predominantly. During alkylation in acetic acid, besides N9-, N3-, and N7-alkylation products were also isolated. Alkylation of 6-[alkyl(dialkyl)amino]purines with phenyl glycidyl ether in DMF produced N-exo substituted 9-(2-hydroxy-3-phenoxypropyl)adenine analogues.

1-methylpurine-4-methyleneandrostane-triazole derivative, synthesis method and application thereof

The invention belongs to the technical field of medicinal chemistry, and relates to a 1- methylpurine-4- methyleneandrostane-triazole derivative with anticancer activity. The compound has the generalformula as shown in the specification. The derivative of the invention is prepared by using a 6-chloropurine compound as a raw material and through nucleophilic reaction, halogenation, azidation, cycloaddition and a Claisen-Schmidt condensation reaction. The preparation method is simple and the conditions are mild. These compounds have obvious inhibitory effects on cell lines such as gastric cancer and prostate cancer, can be used for preparing antitumor drugs, and provide a lead compound structure for further research on anticancer drugs.

HFIP Promoted Low-Temperature SNAr of Chloroheteroarenes Using Thiols and Amines

A highly efficient and an unprecedented hexafluoro-2-propanol, promoting low-temperature aromatic nucleophilic substitutions of chloroheteroarenes, has been performed using thiols and (secondary) amines under base-free and metal-free conditions. The developed protocol also provides excellent regio-control for the selective functionalization of dichloroheteroarenes, while the utility of the protocol was demonstrated by the modification of a commercially available drug ceritinib.

Pd/PTABS: Catalyst for Room Temperature Amination of Heteroarenes

A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib intermediate as well as the formal synthesis of Alogliptin in competitive yields.

Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove

A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus (MIC = 4 μg/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c–DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity.

Design and optimization of purine derivatives as in vivo active PDE10A inhibitors

Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2-a]pyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity. And after further PDE enzymatic selectivity study, metabolic stability assay and in vivo pharmacological tests we identified two inhibitors as interesting lead compounds with the potential for further PDE10A lead optimizatioin.

Synthesis of Chiral Cyclopropyl Carbocyclic Purine Nucleosides via Asymmetric Intramolecular Cyclopropanations Catalyzed by a Chiral Ruthenium(II) Complex

The synthesis of chiral cyclopropyl carbocyclic purine nucleoside analogues via the highly enantioselective intramolecular cyclopropanation reactions has been reported. With a chiral ruthenium(II)-phenyloxazoline complex as the catalyst, cyclopropyl carbocyclic purine nucleoside analogues containing three contiguous stereocenters were obtained with up to 99% yield and 99% ee. Furthermore, a chiral cyclopropyl carbocyclic adenosine nucleoside having anti-BLV activity could be synthesized in a concise manner using this strategy. (Figure presented.).