2465-59-0

Usage

Uses

Used in Enzyme Research:
4,6-Dihydroxy-1H-pyrazolo[3,4-d]pyrimidine is used as an inhibitor to study the specificity and kinetics of xanthine oxidase. This application is crucial for understanding the enzyme's role in various biological processes and its potential as a therapeutic target.
Used in Anti-Inflammatory Applications:
As an anti-inflammatory agent, 4,6-Dihydroxy-1H-pyrazolo[3,4-d]pyrimidine inhibits xanthine oxidase, which is involved in the production of pro-inflammatory mediators. This inhibition can help reduce inflammation and alleviate symptoms associated with various inflammatory conditions.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 4,6-Dihydroxy-1H-pyrazolo[3,4-d]pyrimidine is used as a key intermediate in the synthesis of various therapeutic agents, particularly those targeting xanthine oxidase-related diseases. Its unique chemical properties make it a valuable compound for drug development and design.
Used in Biochemical Research:
4,6-Dihydroxy-1H-pyrazolo[3,4-d]pyrimidine is also utilized in biochemical research to investigate the mechanisms of action of various enzymes and their interactions with other biomolecules. This research can contribute to the development of novel therapeutic strategies and a deeper understanding of biological processes.

Biological Activity

oxipurinol is a xanthine oxidoreductase inhibitor.xanthine oxidoreductase (xo), a complex molybdoflavoenzyme present in milk and many other tissues, has been studied for many years. xo is generally recognized as a critical enzyme in purine catabolism.

Biochem/physiol Actions

An allopurinol metabolite.

in vitro

allopurinol could be rapidly oxidized by xo to its active metabolite oxypurinol (both isosteres of hypoxanthine and xanthine, respectively), which also could inhibit xo. oxypurinol was identified as a noncompetitive inhibitor of xo; the formation of 4,6-DIHYDROXYPYRAZOLO[3,4-D]PYRIMIDINE was reported to be responsible for much of the pharmacological activity of allopurinol. moreover, both allopurinol and oxypurinol showed free radical scavenging effects in isolated hearts, and exerted cardioprotective effects despite no detectable xo activities [1].

in vivo

animal study found that in the vasculature of hypercholesterolemic rabbits, oxypurinol treatment led to a decrease in vascular free radical production [1].

references

[1] p. pacher, a. nivorozhkin and c. szabó. therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. pharmacological reviews 58(1), 87-114 (2006).[2] day ro, graham gg, hicks m, mclachlan aj, stocker sl, williams km. clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. clin pharmacokinet. 2007;46(8):623-44.

InChI:InChI=1/C5H4N4O2/c10-4-2-1-6-9-3(2)7-5(11)8-4/h1H,(H3,6,7,8,9,10,11)

Upstream product

• 27511-79-1 3-amino-4-pyrazolocarboxamide hemisulfate 
• 57-13-6 urea 
• 98277-30-6 4,6-dimethoxy-1H-pyrazolo[3,4-d]pyrimidine 
• 315-30-0 4-hydroxypyrazolo(3,4-d)pyrimidine 
• 1336-21-6 ammonium hydroxide 
• 35344-99-1 3,4-pyrazole dicarboxylic acid 
• 21272-56-0 1⁽²⁾H-pyrazole-3,4-dicarboxylic acid diamide 
• 75-65-0 tert-butyl alcohol 
• 5334-31-6 5-amino-1H-pyrazole-4-carboxylic acid amide 
• 24521-76-4 6-thioxo-1,5,6,7-tetrahydropyrazolo<3,4-d>pyrimidin-4-one 
• 134221-52-6 4-chloro-2,6-dimethoxypyrimidine-5-carboxaldehyde 
• 246855-09-4 N-benzylidene-N'-(6-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-hydrazine 
• 246855-07-2 6-Chloro-4-hydrazino-1H-pyrazolo[3,4-d]pyrimidine 
• 152422-99-6 6-phenacylthio-pyrazolo<3,4-p>pyrimidine 

Downstream Products

• 5334-33-8 4,5-Dihydro-4-thioxo-1H-pyrazolo[3,4-d]pyrimidin-6(7H)-one 
• 42754-96-1 4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine 
• 139004-10-7 2-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)pyrazolo<3,4-d>pyrimidine-4,6(5H,7H)-dione 
• 139004-08-3 7-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)pyrazolo<3,4-d>pyrimidine-4,6(1H,5H)-dione 
• 246855-16-3 5-chloro-3-phenyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 246855-18-5 5-chloro-3-(4-chloro-phenyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 246855-17-4 5-chloro-3-(4-fluoro-phenyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 246855-19-6 5-chloro-3-p-tolyl-7H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 246855-20-9 5-chloro-3-(4-methoxy-phenyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 246855-21-0 5-chloro-3-(4-nitro-phenyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidine 
• 139004-12-9 4-Amino-7-((2R,3S,4R,5R)-3,4-bis-benzyloxy-5-benzyloxymethyl-tetrahydro-furan-2-yl)-1,7-dihydro-pyrazolo[3,4-d]pyrimidin-6-one 
• 139004-04-9 7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-6-oxopyrazolo<3,4-d>pyrimidine-4(1H,5H)-thione 

Relevant academic research and scientific papers

Control of xanthine oxidase activity by light

Turning the light on and off can control the activity of xanthine oxidase (XOD) when allopurinol (1) is the substrate. Alloxanthin (2) is formed in the reaction but also acts as an inhibitor of the enzyme. Irradiation can free the active site and let the enzyme get on with its job. The alloxanthin - XOD system might have important future applications as a photoswitch/integrator in molecular-scale optobioelectronic devices.

FYX-051: A novel and potent hybrid-type inhibitor of xanthine oxidoreductase

4-[5-(Pyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile (FYX-051) is a potent inhibitor of bovine milk xanthine oxidoreductase (XOR). Steady-state kinetics study showed that it initially behaved as a competitive-type inhibitor with a Ki value of 5.7 × 10 -9 M, then after a few minutes it formed a tight complex with XOR via a Mo-oxygen-carbon atom covalent linkage, as reported previously (Proc Natl Acad Sci USA 101:7931-7936, 2004). Thus, FYX-051 is a hybrid-type inhibitor exhibiting both structure- and mechanism-based inhibition. The FYX-051-XOR complex decomposed with a half-life of 20.4 h, but the enzyme activity did not fully recover. This was found to be caused by XOR-mediated conversion of FYX-051 to 4-[5-(2-hydroxypyridin-4-yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile (2-hydroxy-FYX-051), as well as formation of 6-hydroxy-4-[5-(2-hydroxypyridin-4- yl)-1H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile (dihydroxy-FYX-051) and 4-[5-(2,6-dihydroxypyridin-4-yl)-1H-1,2,4-triazol-3-yl]-6-hydroxypyridine-2- carbonitrile (trihydroxy-FYX-051) during prolonged incubation for up to 72 h. A distinct charge-transfer band was observed concomitantly with the formation of the trihydroxy-FYX-051-XOR complex. Crystallographic analysis of the charge-transfer complex indicated that a Mo-nitrogen-carbon bond was formed between molybdenum of XOR and the nitrile group of trihydroxy-FYX-051. FYX-051 showed a potent and long-lasting hypouricemic effect in a rat model of potassium oxonate-induced hyperuricemia, and it seems to be a promising candidate for the clinical treatment of hyperuricemia. Copyright

Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies

A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10?μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50values of 1.30?μM, 1.43?μM, 2.38?μM and 2.18?μM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).

Chemo- and regioselective functionalization of uracil derivatives. Applications to the synthesis of oxypurinol and emivirine

A novel route for the synthesis of 4,5-difunctionalized uracils using a chemo- and regioselective bromine/magnesium exchange reaction on 5-bromo-4-halogeno-2,6-dimethoxypyrimidines has been developed. Applications to the synthesis of pharmaceuticals such as oxypurinol and emivirine are reported.

PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES

Compounds of formula (I): and their use in the inhibition of Trk activity are described.

Novel xanthine oxidase inhibitor studies. Part 3. Convenient and general syntheses of 3-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-5(6H)-ones as a new class of potential xanthine oxidase inhibitors

Convenient and general syntheses of 3-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-5(6H)-ones (12), a new class of potent xanthine oxidase inhibitors, involving the oxidative cyclisation of 6-substituted 4-alkylidenehydrazino- or 4-arylmethylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines (3 and 11) with 70% nitric acid as the key step, are reported. The hydrazones 3 and 11 were obtained by a versatile synthetic route via the key intermediates, 6-chloro-4-hydrazino-1H-pyrazolo[3,4-d]pyrimidine 2 or oxypurinol 4, starting from 2,4,6-trichloropyrimidine-5-carbaldehyde 1. Their inhibitory activities against bovine milk xanthine oxidase in vitro are also described; i.e. the pyrazolotriazolopyrimidines 12 were several hundred times more potent than allopurinol.

Facile and general syntheses of 3- and/or 5-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidines as a new class of potential xanthine oxidase inhibitors

Convenient syntheses of 3- and/or 5-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidines as a new class of potent xanthine oxidase inhibitors, involving the oxidative cyclisation of 4-alkylidenehydrazino- or 4-arylmethylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines with 70% nitric acid as the key step, are described.

Pyrazolothiazolopyrimidine derivatives as a novel class of anti-inflammatory or antinociceptive agents: synthesis, structural characterization and pharmacological evaluation

As a part of a research program on anti-inflammatory-analgesic compounds, pyrazolothiazolopyrimidines 5a-f and 5g-i were prepared by cyclodehydration in 98percent H2SO4 or PPA of the corresponding 6-thioketomethylene-substituted-4-hydroxypyrazolopyrimidinies 2a-i and 2g-i.The results of the pharmacological in vivo screening indicate an interesting dissociation of the analgesic from the anti-inflammatory activity depending on aromatic or aliphatic substitution at C4 of the thiazole ring.Analgesic activity was not associated with any narcotic affect: in addition, all th e active compounds showed a remarkable systemic and gastric tolerance.This indicated a mode of action different from that of the classical nonsteroidal anti-inflammatory drugs, acting on prostaglandin biosynthesis.To clarify the mechanism or the mechanisms underlying the pharmacological activity of these and other closely related compounds, we initiated a 'file chemical approach' to various systems involved in the inflammatory process.At present, some of the more active in vivo compounds tested as substance P antagonists showed a moderate and possibly non-specific effect on NK1 and NK2 receptors. pyrazolothiazolopyrimidine derivatives / anti-inflammatory-analgesic activity / substance P antagonists