37893-08-6

Usage

Uses

Used in Pharmaceutical Research and Drug Development:
2,4(1H,3H)-Pyrimidinedione, 6-methyl-, 2-hydrazone (9CI) is used as a building block or precursor for the synthesis of biologically active compounds. Its unique structural characteristics make it a promising candidate for the development of new pharmaceutical agents with potential medicinal or biological properties.
Used in Agricultural Applications:
Although further research is needed, 2,4(1H,3H)-Pyrimidinedione, 6-methyl-, 2-hydrazone (9CI) may have potential uses in agriculture, possibly as a component in the development of new agrochemicals or as a tool for studying plant-microbe interactions.
Used in Industrial Applications:
Similarly, the compound may have potential industrial applications, but more research is required to determine its specific uses and implications in various industrial processes. Its unique chemical properties could potentially be harnessed for the development of new materials or technologies.

InChI:InChI=1/C5H8N4O/c1-3-2-4(10)8-5(7-3)9-6/h2H,6H2,1H3,(H2,7,8,9,10)

Upstream product

• 56-04-2 6-methyl-2-thiouracil 
• 6328-58-1 6-methyl-2-methylsulfanyl-3H-pyrimidin-4-one 
• 6328-58-1 6-methyl-2-methylthiopyrimidin-4-one 
• 21418-88-2 ethyl 2-[(6-methyl-4-oxo-3,4-dihydropyrimidin-2-yl)thio]acetate 
• 56-04-2 2-mercapto-6-methylpyrimidin-4(3H)-one 
• 3019-18-9 2-(ethylsulfanyl)-6-methylpyrimidin-4(3H)-one 
• 53736-37-1 2-nitroamino-4(3H)-pyrimidinone 

Downstream Products

• 90916-79-3 furfural-(4-methyl-6-oxo-1,6-dihydro-pyrimidin-2-ylhydrazone) 
• 65894-19-1 E-2-[2-(4-chlorobenzylidene)hydrazinyl]-6-methylpyrimidin-4-one 
• 92023-96-6 E-2-[2-(4-methoxybenzylidene)hydrazinyl]-6-methylpyrimidin-4-one 
• 66680-02-2 4-dimethylamino-benzaldehyde-(4-methyl-6-oxo-1,6-dihydro-pyrimidin-2-ylhydrazone) 
• 79871-84-4 6-chloro-1-<4-(N-n-butylanilino)-6-methyl-2-pyrimidinyl>-3,4-dimethyl-1H-pyrazolo<3,4-b>pyridine 
• 91843-75-3 E-2-[2-(4-nitrobenzylidene)hydrazinyl]-6-methylpyrimidin-4-one 
• 66680-03-3 E-2-[2-(2-hydroxybenzylidene)hydrazinyl]-6-methylpyrimidin-4-one 
• 100953-63-7 4-bromo-benzaldehyde-(4-methyl-6-oxo-1,6-dihydro-pyrimidin-2-ylhydrazone) 

Relevant academic research and scientific papers

SYNTHESIS AND STUDY OF HETEROAROMATIC LIGANDS CONTAINING A PYRIMIDINE RING

5-Hexyl-3-amino-1(2)H-1,2,4-triazoles and 2-(3,5-dipropyl-4-ethyl-1H-pyrazol-1-yl)-6-methyl-4-(5-methyl-1H-pyrazol-1-yl)aminopyrimidine were synthesized by the reaction of 4-chloropyrimidines with 3-amino-5-hexyl-1H-1,2,4-triazole and 3-amino-5-methyl-1H-pyrazole.Their IR, UV, and PMR spectra were investigated.New methods for the preparation of the intermediates, viz., 2-hydrazino-4(3H)-pyrimidinones and 2-(1H-pyrazol-1-yl)-4(3H)-pyrimidinones, that make it possible to obtain these compounds in higher yields are described.

Synthesis of 2-(pyrazol-1-yl)pyrimidine derivatives by cyclocondensation of ethyl acetoacetate (6-methyl-4-oxo-3,4-dihydropyrimidin-2-yl)hydrazone with aromatic aldehydes

2-(4-Arylidene-3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-6-methylpyrimidin- 4(3H)-ones were obtained by reaction of ethyl acetoacetate (6-methyl-4-oxo-3,4- dihydropyrimidin-2-yl)hydrazone with aromatic aldehydes. Successful cyclization occurs with aldehydes containing an auxochromic substituent in the para position.

Synthesis, antibacterial, antioxidant, and molecular docking studies of 6-methylpyrimidin-4(3H)-one and oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives

A series of 6-methylpyrimidin-4(3H)-one and oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives (1-18) was designed to meet the urgent need for novel antibacterial and antioxidant agents. The in vitro antibacterial activity revealed that most of the compounds exhibited a good inhibitory effect on Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria with MIC values in the range of 55–200 μg/mL for E. coli and 125–700 μg/mL for S. aureus. (E)-2-(2-(4-methoxybenzylidene)hydrazinyl)-6-methylpyrimidin-4(3H)-one (8) was the most active compound (MIC = 55 and 125 μg/mL against E. coli and S. aureus, respectively). All compounds exhibited antioxidant activity ranged from weak to moderate and high. The obtained findings revealed that compounds 3, 5, 6, 9, 16, and 18 have superiority among all compounds, demonstrating the highest capacity to deplete DPPH (1,1-diphenyl-2-picrylhydrazyl), compared to α-tocopherol, as a standard antioxidant agent. Surprisingly, compound 3 (2-hydrazinyl-6-methylpyrimidin-4(3H)-one) showed significantly higher antioxidant activity (EC50 = 2.12 μg/mL) than α-tocopherol (EC50 = 9.16 μg/mL). Molecular docking, drug-likeness data, physicochemical properties, and ADMET parameters of the compounds were in silico computed. The derivatives presented good properties for Lipinski's parameters, poor solubility in the aqueous medium (Log S of -1.27 to -5.45), and PSA ≤140, indicating good permeability in biological membranes and gastrointestinal absorption. Molecular docking to the active sites of penicillin-binding protein and NADPH oxidase revealed that most compounds displayed minimal binding energy and have a good affinity toward the active pocket.

Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies

Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.

NOVEL ANTIPARASITIC COMPOUNDS AND METHODS

Novel compounds for treating or inhibiting leishmaniasis and other parasitic protozoan diseases are disclosed herein. The compounds bind to Leishmania tubulin, induce parasite microtubule polymerization, stall Leishmania cell division, and have broad antiparasitic activity.

Structure-based design and optimization of pyrimidine- and 1,2,4-triazolo[4,3-a]pyrimidine-based matrix metalloproteinase-10/13 inhibitors via Dimroth rearrangement towards targeted polypharmacology

Recently, interest in matrix metalloproteinases (MMPs) -10 and -13 has been revitalized with the growing knowledge on their relevance within the MMPs network and significance of their inhibition for treatment of various diseases like arthritis, cancer, atherosclerosis and Alzheimer. Within this approach, dual MMP-10/13 inhibition was disclosed as new approach for targeted polypharmacology. While several efficient MMP-13 inhibitors are known, very few potent and selective MMP-10 inhibitors were reported. This study describes the design, synthesis and optimization of novel MMP-10/13 inhibitors with enhanced MMP-10 potency and selectivity towards polypharmacology. Starting with a lead fused pyrimidine-based MMP-13 inhibitor with weak MMP-10 inhibition, a structure-based design of pyrimidine and fused pyrimidine scaffolds was rationalized to enhance activity against MMP-10 in parallel with MMP-13. Firstly, a series of 6-methyl pyrimidin-4-one hydrazones 6–10 was synthesized via conventional and ultrasonic-assisted methods, then evaluated for MMP-10/13 inhibition. The most active derivative 9 exhibited acceptable dual potency with 7-fold selectivity for MMP-10 (IC50 = 53 nM) over MMP-13. Such hydrazones were then cyclized to the corresponding isomeric 1,2,4-triazolo[4,3-a]pyrimidines 12–19. Their MMP-10/13 inhibition assay revealed, in most cases, superior dual activities with general MMP-10 selectivity compared to the corresponding precursors 6–10. In addition, a clear structure activity relationship trend was deduced within the identified regioisomers, where the 5-oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives 15 and 16 were far more active against MMP-10/13 than their regioisomers 12 and 13. Remarkably, the p-bromophenyl derivative 16 exhibited the highest MMP-10 inhibition (IC50 = 24 nM), whereas the p-methoxy derivative 18 was the most potent MMP-13 inhibitor (IC50 = 294 nM). Moreover, 16 exhibited 19-fold selectivity for MMP-10 over MMP-13, 10-fold over MMP-9, and 29-fold over MMP-7. Docking studies were performed to provide reasonable explanation for structure-activity relationships and isoform selectivity. 16 and 18 were then evaluated for their anticancer activities against three human cancers to assess their therapeutic potential at cellular level via MTT assay. Both compounds exhibited superior anticancer activities compared to quercetin. Their in silico ligand efficiency metrics, physicochemical properties and ADME parameters were drug-like. Guided by such findings that point to 16 as the most promising compound in this study, further structure optimization was carried out via photoirradiation-mediated Dimroth rearrangement of the inactive triazolopyrimidine 13 to its potent regioisomer 16.

NOVEL SCAFFOLD OF ADENYLYL CYCLASE INHIBITORS FOR CHRONIC PAIN AND OPIOID DEPENDENCE

The present invention relates to a method of treatment for chronic pain, opioid dependence, alcohol use disorder or autism using a class of pyrimidinone compounds, an adenylyl cyclase 1 (AC1) inhibitor. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases in mammals using those compounds disclosed herein.

HETEROARYL DERIVATIVES AS SEPIAPTERIN REDUCTASE INHIBITORS

Inhibitors of sepiapterin reductase of formula (I) or (I'), wherein the substituents are defined as in the claims, and uses of sepiapterin reductase inhibitors in analgesia, treatment of acute and chronic pain, anti-inflammation, and immune cell regulation are disclosed.

PROTEOSTASIS REGULATORS FOR TREATING CYSTIC FIBROSIS AND OTHER PROTEIN MISFOLDING DISEASES

The present invention is directed to compounds of Formulae (Ia-Ib), (Ila-IId), (Illa- Illb), (IV), (V), (VI), (Vlla-VIIc), (VIII), (IXa-IXb), (Xa-Xb), (XIa-XIb) and (Xlla-XIIb), pharmaceutical compositions thereof and methods of use thereof in the treatment of conditions associated with a dysfunction in proteostasis.

Amino-substituted pyrimidines, derivatives and methods of use therefor

The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.