2503-56-2

Usage

Uses

Used in Pharmaceutical Industry:
7-Hydroxy-5-methyl-1,3,4-triazaindolizine is used as a reactant for the synthesis of Ruthenium(II)-Hmtpo complexes, which have potential applications in medicinal chemistry and drug development.
Used in Antimalarial Drug Development:
7-Hydroxy-5-methyl-1,3,4-triazaindolizine is used as a reactant for the synthesis of dihydroorotate dehydrogenase inhibitors with antimalarial activity, contributing to the development of new treatments for malaria.
Used in Organic Chemistry:
7-Hydroxy-5-methyl-1,3,4-triazaindolizine is used as a reactant for the Vilsmeier reaction of conjugated carbocycles and heterocycles, which is an important method for the synthesis of various organic compounds.
Used in HIV Research:
7-Hydroxy-5-methyl-1,3,4-triazaindolizine is used in investigations of the pharmacological activity caused by binding to HIV TAR RNA, which can help in understanding the mechanisms of HIV infection and the development of antiviral agents.
Used in Material Science:
7-Hydroxy-5-methyl-1,3,4-triazaindolizine is used as an additive to study the space charge layer in silver bromide microcrystals, which can contribute to the advancement of materials with specific properties for various applications.

InChI:InChI=1/C7H7N3O/c1-5-2-6(11)3-7-8-4-9-10(5)7/h2-4,11H,1H3

Upstream product

• 141-97-9 ethyl acetoacetate 
• 61-82-5 3-amino-1,2,4-triazole 
• 61-82-5 3⁽⁵⁾-amino-1,2,4-triazole 
• 61-82-5 4H-1,2,4-triazol-3-amine 

Downstream Products

• 892253-50-8 5-methyl-7-(piperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidine 
• 33376-96-4 5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine 
• 898478-91-6 (2-fluorophenyl)(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amine 
• 56347-09-2 5-methyl-7-phenyl-[1,2,4]triazolo[1,5-a]pyrimidine 

Relevant academic research and scientific papers

Quinoline carboxamide core moiety-based compounds inhibit P. falciparum falcipain-2: Design, synthesis and antimalarial efficacy studies

Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC50 4.78, 7.37, 2.14 and 2.64 μM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.

A multifunctional therapeutic approach: Synthesis, biological evaluation, crystal structure and molecular docking of diversified 1H-pyrazolo[3,4-b]pyridine derivatives against Alzheimer's disease

2-(piperazin-1-yl)–N-(1H-pyrazolo[3,4-b]pyridin-3-yl)acetamides are described as a new class of selective and potent acetylcholinesterase (AChE) inhibitors and amyloid β aggregation inhibitors. Formation of synthesized compounds (P1–P9) was justified via H1 NMR, C13 NMR, mass spectra and single crystal X-Ray diffraction study. All compounds were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity, inhibition of self-mediated Aβ aggregation and Cu(II)-mediated Aβ aggregation. Also, docking study carried out was in concordance with in vitro results. The most potent molecule amongst the derivatives exhibited excellent anti-AChE activity (IC50 = 4.8 nM). Kinetic study of P3 suggested it to be a mixed type inhibitor. In vitro study revealed that all the compounds are capable of inhibiting self-induced β-amyloid (Aβ) aggregation with the highest inhibition percentage to be 81.65%. Potency of P1 and P3 to inhibit self-induced Aβ1-42 aggregation was ascertained by TEM analysis. Compounds were also evaluated for their Aβ disaggregation, antioxidation, metal-chelation activity.

Pd-catalyzed Suzuki/Sonogashira cross-coupling reaction and the direct sp3 arylation of 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine

A rapid and efficient method is reported for the synthesis of the [1,2,4]triazolo[1,5-a]pyrimidine motif. Palladium catalyzed Suzuki and Sonogashira cross coupling reactions on 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine were performed. The direct sp3 arylation of compounds resulting from the Suzuki reaction was then carried out.

The synthesis and evaluation of triazolopyrimidines as anti-tubercular agents

We identified a di-substituted triazolopyrimidine with anti-tubercular activity against Mycobacterium tuberculosis. Three segments of the scaffold were examined rationally to establish a structure-activity relationship with the goal of improving potency and maintaining good physicochemical properties. A number of compounds displayed sub-micromolar activity against Mycobacterium tuberculosis with no cytotoxicity against eukaryotic cells. Non-substituted aromatic rings at C5 and a two-carbon chain connecting a terminal aromatic at C7 were preferred features; the presence of NH at C7 and a lack of substituent at C2 were essential for potency. We identified compounds with acceptable metabolic stability in rodent and human liver microsomes. Our findings suggest that the easily-synthesized triazolopyrimidines are a promising class of potent anti-tubercular agents and warrant further investigation in our search for new drugs to fight tuberculosis.

Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents

In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC50 values 0.065 and 0.092?μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ～28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy.

Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aβ aggregation and antioxidant activity.

Lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice

Malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance.We previously reported identification of a new class of triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. Active compounds from the series contained a triazolopyrimidine ring attached to an aromatic group through a bridging nitrogen atom. Herein, we describe systematic efforts to optimize the aromatic functionality with the goal of improving potency and in vivo properties of compounds from the series. These studies led to the identification of two new substituted aniline moieties (4-SF5-Ph and 3,5-Di-F-4- CF 3-Ph), which, when coupled to the triazolopyrimidine ring, showed good plasma exposure and better efficacy in the Plasmodium berghei mouse model of the disease than previously reported compounds from the series.

Synthesis, antibacterial and insecticidal activities of a new series of 4-(5-methyl-[1,2,4] triazolo [1,5-a] pyrimidin-7-ylamino)-N-(aryl) benzamides

A nevi/ series of 4-(5-methyl-[1,2,4] triazoio [1,5-a] pyrimidin-7-ylamino) -N-(aryl) benzamides (4a-i) were synthesized by coupling 4-(5-methyl-(1,2,4] triazoio [1,5-a] pyrimidin-7-ylamino) benzoic acid 3 with different substituted amines using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) as coupling reagent. The key intermediate 4-(5-methyl-[1,2,4] triazoio [1,5-a] pyrimidin-7-ylamino) benzoic acid 3 was synthesized by the reaction of 7-chloro-5-methyl-[1,2,4] triazoio [1,5-a] pyrimidine 2 with p-aminobenzoic acid in ethanol. The structure of the newly synthesized compounds were confirmed by FT-IR,1H NMR, 13C NMR and Mass spectral analysis and were evaluated for their antimicrobial and insecticidal activities. Some of the synthesized compounds exhibited potent insecticidal activity and significant antibacterial activity with respect to the standard drugs.

THERAPEUTIC AGENTS

The invention provides a compound of formula (I): wherein R1, and W have any of the values defined in the application; or a salt thereof. The compounds and salts thereof have beneficial therapeutic properties (e.g. immunosuppressant properties).

DIHYDROOROTATE DEHYDROGENASE INHIBITORS WITH SELECTIVE ANTI-MALARIAL ACTIVITY

Compounds according to Formula (I), Formula (II), Formula (III), Formula (V), Formula (VI), or to Formula (VII), and pharmaceutical compositions of compounds that conform to Formula (IV) or (Formula VIII): where R1 through R33 are prescribed, selectively inhibit P. falciparum dihydroorotate dehydrogenase. Accordingly, a method for preventing and treating malaria attaches to such compounds, as well as to pharmaceutically acceptable salts, solvates, stereoisomers, tautomers, and prodrugs thereof.