50-66-8

Usage

Uses

Used in Pharmaceutical Industry:
6-METHYLMERCAPTOPURINE is used as an immunosuppressive agent for the treatment of leukemia. Its application reason is based on its ability to suppress the immune system, which helps in managing the uncontrolled growth of leukemia cells.
Used in Oncology:
In the field of oncology, 6-METHYLMERCAPTOPURINE is used as a therapeutic agent for leukemia patients. The application reason is its immunosuppressive properties, which aid in controlling the proliferation of cancerous cells and improving the patient's response to treatment.
Used in Research and Development:
6-METHYLMERCAPTOPURINE is also utilized as a research compound in the development of new drugs and therapies for various types of cancer. Its application reason lies in its potential to provide insights into the mechanisms of cancer cell growth and the development of targeted treatments.

InChI:InChI=1/C6H6N4S/c1-11-6-4-5(8-2-7-4)9-3-10-6/h2-4H,1H3

Upstream product

• 50-44-2 6H-purine-6-thione 
• 485-80-3 S-adenosyl-L-methionine 
• 6258-60-2 p-methoxybenzylmercaptan 
• 157930-09-1 6-Mercaptopurine 
• 353-43-5 boron dimethyl-trifluoro sulphide 
• 87-42-3 6-chloro-7H-purine 
• 85110-41-4 9-(1-Ethoxyethyl-1)-6-methylthiopurine 
• 157930-09-1 6-Mercaptopurine 
• 342-69-8 6-methylmercaptopurine riboside 
• 14031-35-7 S-Adenosyl-L-methionine 
• 50-44-2 6-mercaptopurine 
• 87-42-3 6-chloropurine 
• 5188-07-8 sodium thiomethoxide 
• 74-88-4 methyl iodide 

Downstream Products

• 525-79-1 kinetin 
• 1669-86-9 [2-(1⁽³⁾H-imidazol-4-yl)-ethyl]-(7⁽⁹⁾H-purin-6-yl)-amine 
• 2846-96-0 6-morpholino-7⁽⁹⁾H-purine 
• 525-81-5 (7(9)H-purin-6-yl)-[2]thienylmethyl-amine 
• 16370-58-4 propyl-(7(9)H-purin-6-yl)-amine 
• 13268-73-0 6-(2-methylbenzylamino)purine 
• 88166-55-6 dodecyl-(7⁽⁹⁾H-purin-6-yl)-amine 
• 36412-32-5 octyl-(7(9)H-purin-6-yl)-amine 
• 14333-96-1 hexyl-(7⁽⁹⁾H-purin-6-yl)-amine 
• 14814-48-3 heptyl-(7(9)H-purin-6-yl)-amine 
• 15500-82-0 (2-phenoxy-propyl)-(7⁽⁹⁾H-purin-6-yl)-amine 
• 20366-83-0 6-(2-hydroxybenzylamino)purine 
• 15500-86-4 (4-phenoxy-butyl)-(7⁽⁹⁾H-purin-6-yl)-amine 
• 15396-43-7 (3-phenyl-propyl)-(7⁽⁹⁾H-purin-6-yl)-amine 

Relevant academic research and scientific papers

Human thiopurine methyltransferase: No evidence of activation by its substrates

A HPLC assay was developed to assay baculovirus expressed human thiopurine methyltransferase activity. Using 6-mercaptopurine as substrate, the expressed thiopurine methyltransferase was found to have an apparent Km of 0.99 mM and a Vmax of 19 nmoles/mg/min. These values are in agreement with those determined using the standard radiometric assay for thiopurine methyltransferase activity. The effects of 6-thioguanine on 6-mercaptopurine metabolism were determined. 6-Thioguanine was found to be a mixed inhibitor of 6-mercaptopurine methylation.

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.

Metal-Free Aminomethylation of Aromatic Sulfones Promoted by Eosin Y

A metal-free α-aminomethylation of heteroaryls promoted by eosin Y under green light irradiation is reported. A large variety of α-trimethylsilylamines as precursor of α-aminomethyl radical species were engaged to functionalize sulfonyl-heteroaryls following a Homolytic Aromatic Substitution (HAS) pathway. This method has provided a range of α-aminoheteroaryl compounds including a functionalized natural product. The mechanism of this late-stage functionalization of aryls was investigated and suggests the formation of a sulfonyl radical intermediate over a reductive quenching cycle.

The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10–15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of ≤50 μM. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein–protein interaction between the molecular chaperone αB-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF165 interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF165, and compound 4e (100 μM) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.

BF3·SMe2 for Thiomethylation, Nitro Reduction and Tandem Reduction/SMe Insertion of Nitrogen Heterocycles

Herein, a general, solvent-free and straightforward thiomethylation of electron deficient heterocycles using BF3·SMe2 as a dual thiomethyl source and Lewis acidic activator is presented. A range of heterocycles including pyrimidine, pyrazine, pyridazine, thiazole and purine derivatives were successfully substituted using this method. An unexpected reductive property of BF3·SMe2 towards nitropyridines was also discovered including an intriguing tandem reduction/SMe insertion process in certain substrates. Notable features of the present work include its convenience and use of a non-malodorous reagent while the discovery of novel chemical transformations using BF3·SMe2 provides fundamental new insights into the reactivity of this commonly employed reagent.

Enzyme-catalyzed transfer of a ketone group from an S-adenosylmethionine analogue: A tool for the functional analysis of methyltransferases

"Chemical equation presented" S-Adenosylmethionine (AdoMet or SAM)-dependent methyltransferases belong to a large and diverse family of group-transfer enzymes that perform vital biological functions on a host of substrates. Despite the progress in genomics, structural proteomics, and computational biology, functional annotation of methyltransferases remains a challenge. Herein, we report the synthesis and activity of a new AdoMet analogue functionalized with a ketone group. Using catechol O-methyltransferase (COMT, EC 2.1.1.6) and thiopurine S-methyltransferase (TPMT, EC 2.1.1.67) as model enzymes, this robust and readily accessible analogue displays kinetic parameters that are comparable to AdoMet and exhibits multiple turnovers with enzyme. More importantly, this AdoMet surrogate displays the same substrate specificity as the natural methyl donor. Incorporation of the ketone group allows for subsequent modification via bio-orthogonal labeling strategies and sensitive detection of the tagged ketone prod cts. Hence, this AdoMet analogue expands the toolbox available to interrogate the biochemical functions of methyltransferases.

An efficient synthesis of substituted cytosines and purines under focused microwave irradiation

A rapid nucleophilic displacement reaction of 6-chloropurine, 2-amino-6-chloropurine and 5-bromocytosine with various nucleophiles under focused microwave irradiation is described. Using this method, the desired products were obtained with the yields up to 99% in?a?short reaction time.

Gene therapy of cancer: activation of nucleoside prodrugs with e. colipurine nucleoside phosphorylase

During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery of E. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. .This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data. Copyright

Methylation of mercaptopurine, thioguanine, and their nucleotide metabolites by heterologously expressed human thiopurine S-methyltransferase

Thiopurine S-methyltransferase (TPMT), a cytosolic enzyme that exhibits genetic polymorphism, catalyzes S-methylation of mercaptopurine (MP) and thioguanine (TG), yielding S-methylated nucleobases that are inactive, whereas S-methylated nucleotides of these thiopurines are cytotoxic. A yeast- based heterologous expression system was therefore used to characterize human TPMT-catalyzed methylation of MP, TG, and their principal nucleotide metabolites [thioinosine monophosphate (TIMP) and thioguanosine monophosphate (TGMP), respectively]. MP, TG, TIMP, and TGMP were all substrates for human TPMT, exhibiting similar Michaelis-Menten kinetic parameters (K(m), 10.6- 27.1 μM; V(max), 31-59 nmol/min/mg of TPMT). Consistent with these kinetic parameters, human leukemia cells (CEM) incubated for 24 hr with 10 μM MP or TG accumulated significantly higher (2.3-fold, p = 0.01) concentrations of methyl-TIMP after MP incubation than methyl-TGMP after TG incubation, due to the 2.7-fold higher concentration of TIMP after MP incubation, compared with TG nucleotides (TGN) after TG incubation. Moreover, intracellular accumulation of TGN was 2.5-fold greater after TG incubation than after MP incubation (p = 0.01). These data establish that MP, TG, and their principal nucleotide metabolites are comparable substrates for polymorphic TPMT, and they demonstrate significant differences in the accumulation of active TGN and methylated nucleotides when leukemia cells are treated with MP versus TG.

DEAMINATION, INVOLVING RING OPENING, IN REACTIONS OF 1-AMINOPURINIUM MESITYLENESULFONATES WITH METHANOLIC AMMONIA

On reaction of 1-aminopurinium mesitylenesulfonates with methanolic ammonia N-deamination occurs.For 1-amino-, 1-amino-8-(methylthio)-, 1-amino-8-phenyl-, 1-amino-2-methyl-, 1-amino-6-methyl- and 1-amino-8-phenyl-9-methylpurinium mesitylenesulfonate this reaction proceeds for at least 75percent via ring opening as shown by the isolation of 1-15N-labelled purines when 15N-labelled methanolic ammonia was used. 1-Amino-9-methylpurinium mesitylenesulfonate gave N-deamination without ring opening.The reaction of 1-amino-6-(methylthio)purinium mesitylenesulfonate with methanolic ammonia involves, besides deamination, partial substitution of the methylthio group; no ring opening is involved.However, ring opening followed by substitution occurs in the reaction of 1-amino-2-(methylthio)purinium mesitylenesulfonate; the reaction proceeds via an adduct at position 2.