Tag: M.W=150-200

da Silva, Edson R. published the artcileNovel Selective Inhibitor of Leishmania (Leishmania) amazonensis Arginase, Category: triazoles, the main research area is Leishmania leishmaniasis leishmanicide; Leishmania; arginase; polyamines; triazolopyrimidine; trifluoromethyl; trypanothione.

Arginase is a glycosomal enzyme in Leishmania that is involved in polyamine and trypanothione biosynthesis. The central role of arginase in Leishmania amazonensis was demonstrated by the generation of two mutants: one with an arginase lacking the glycosomal addressing signal and one in which the arginase-coding gene was knocked out. Both of these mutants exhibited decreased infectivity. Thus, arginase seems to be a potential drug target for Leishmania treatment. In an attempt to search for arginase inhibitors, 29 derivatives of the [1,2,4]triazolo[1,5-a]pyrimidine system were tested against Leishmania amazonensis arginase in vitro. The [1,2,4]triazolo[1,5-a]pyrimidine scaffold containing CF3 substituent exhibited greater activity against the arginase compared to one with Me substituent in the 2-position. The novel compound I was the most potent, inhibiting arginase by a noncompetitive mechanism, with the Ki and IC50 values for arginase inhibition estimated to be 17±1 μM and 16.5±0.5 μM, resp. These results can guide the development of new drugs against leishmaniasis based on [1,2,4]triazolo[1,5-a]pyrimidine derivatives targeting the arginase enzyme.

Chemical Biology & Drug Design published new progress about Homo sapiens. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Category: triazoles.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Zuniga, Edison S. published the artcileThe synthesis and evaluation of triazolopyrimidines as anti-tubercular agents, Synthetic Route of 24415-66-5, the main research area is triazolo pyrimidine derivative preparation tuberculosis structure; Anti-tubercular activity; Mycobacterium tuberculosis; Triazolopyrimidines; Tuberculosis.

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 physicochem. 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.

Bioorganic & Medicinal Chemistry published new progress about Homo sapiens. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Synthetic Route of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Hughes, Samantha J. published the artcileFragment based discovery of a novel and selective PI3 kinase inhibitor, COA of Formula: C6H5ClN4, the main research area is PI3 kinase inhibitor imidazopyridine preparation SAR.

We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochem. screening, followed by a round of virtual screening to identify addnl. ligand efficient fragments. These were developed into potent and ligand efficient lead compounds using structure guided fragment growing and merging strategies. This led to a potent, selective, and cell permeable PI3γ kinase inhibitor, 12 (I), with good metabolic stability that was useful as a preclin. tool compound

Bioorganic & Medicinal Chemistry Letters published new progress about Drug design. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, COA of Formula: C6H5ClN4.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Zhang, Qian published the artcileDiscovery of Triazolo-pyridazine/-pyrimidine Derivatives Bearing Aromatic (Heterocycle)-Coupled Azole Units as Class II c-Met Inhibitors, SDS of cas: 24415-66-5, the main research area is triazolopyridazine triazolopyrimidine preparation cMet kinase inhibition SAR anticancer human.

Two series of novel triazolo-pyridazine/-pyrimidine derivatives were designed, synthesized, and evaluated for their inhibitory activity against c-Met kinase, as well as three c-Met overexpressed cancer cell lines (A549, MCF-7, and HeLa) and one normal human hepatocytes cell line LO2 in vitro. The most promising compound I exhibited significant cytotoxicity against A549, MCF-7, and HeLa cell lines with IC50 values of 1.06 +/- 0.16, 1.23 +/- 0.18, and 2.73 +/- 0.33μM, resp. Moreover, the inhibitory activity of compound I against c-Met kinase (IC50 = 0.090μM) was equal to that of Foretinib (IC50 = 0.019μM). The result of the acridine orange single staining test demonstrated that compound I could remarkably induce apoptosis of A549 cells. The results of apoptosis and cycle distribution of cells showed that compound I could induce late apoptosis of A549 cells and stimulate A549 cells arresting in the G0/G1 phase. Structure-activity relationships (SARs), pharmacol. results, and docking studies indicated that the introduction of 5-methylthiazole fragment to the five-atom moiety was beneficial for the activity. So far, the existing data indicated that I may become a potential class II c-Met inhibitor.

ACS Omega published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, SDS of cas: 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Jameel, Ehtesham published the artcileRational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents, Application In Synthesis of 24415-66-5, the main research area is triazine triazolopyrimidine preparation antialzheimer antioxidant SAR mol docking human; ADME analysis; Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Molecular docking; Triazine; Triazolopyrimidine quinoline.

A series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Among the synthesized compounds, the di-substituted triazine-triazolopyrimidine derivatives I (R1 = 3-F3CC6H4NH2, 4-MeOC6H4NH2, 4-FC6H4NH2, 2-FC6H4NH2) showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives Out of the disubstituted triazine-triazolopyrimidine based compounds, I (R1 = 3-F3CC6H4NH2) and I (R1 = 4-MeOC6H4NH2) showed encouraging inhibitory activity on AChE with IC50 values 0.065 and 0.092 μM, resp. and they also demonstrated good inhibition selectivity towards AChE over BuChE by ~28 folds. Furthermore, kinetic anal. and mol. modeling studies of these compounds targeted 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 antioxidant (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 mols. qualified them as potential anti-Alzheimer drug candidates in AD therapy.

European Journal of Medicinal Chemistry published new progress about Alzheimer disease. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Application In Synthesis of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Kumar, Jitendra published the artcileSynthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer’s disease therapies, Application In Synthesis of 24415-66-5, the main research area is triazolopyrimidine quinoline hybrid preparation acetylcholinesterase inhibitory activity Alzheimer; cyanopyridine quinoline hybrid preparation acetylcholinesterase inhibitory activity Alzheimer; Acetylcholinesterase; Alzheimer’s disease; Butyrylcholinesterase; Molecular docking; Quinoline; Triazolopyrimidine.

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Mol. docking and scoring was utilized for the design of inhibitors. The mols. were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Et 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (I), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound I 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.

European Journal of Medicinal Chemistry published new progress about Alzheimer disease. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Application In Synthesis of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Kumar, Jitendra published the artcilePyrimidine-Triazolopyrimidine and Pyrimidine-Pyridine Hybrids as Potential Acetylcholinesterase Inhibitors for Alzheimer’s Disease, Name: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is pyrimidine triazolopyrimidine preparation Alzheimer disease acetylcholinesterase inhibitor.

Synthesis and testing of pyrimidine derivatives in conjugation with triazolopyrimidine I [R = [(6-bromonaphthalen-2-yl)oxy], (4-nitrophenyl)aminyl, (naphthalen-2-yloxy)] based hybrid scaffold of AChE inhibitors for development of new mols. towards the treatment of AD were reported. A multipronged approach employing computational, chem. and biol. approaches was used to find the best inhibitor of AChE. Three mols. (2-(4-(6-chloropyrimidin-4-yl)piperazin-1-yl)nicotinonitrile, I (R = [(6-bromonaphthalen-2-yl)oxy]) and II) derived from this scaffold inhibited AChE in nanomolar to micromolar range. Highest activity was shown by II which has IC50 value of 36 nM. Inhibitory effect of II was stronger for human AChE in neuronal cell extract compared to eelAChE. This activity is comparable to donepezil (IC50 = 38nM) which is considered as good standard among AChE inhibitors. The inhibitory activity of II was also in agreement with mol. simulation studies which showed stable interaction of the II with the catalytic active site as well as peripheral anionic site. Mol. simulation studies also indicated stronger interaction of II with rhAChE than TcAChE. This was later confirmed in studies with neuronal cell extract where compound II showed enzyme inhibition at 25 nM. Further this mol. was not found to be toxic or carcinogenic.

ChemistrySelect published new progress about Alzheimer disease. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Name: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Martinez-Viturro, Carlos M. published the artcileDiazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders, Recommanded Product: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is azaspirononane OGA inhibitor neurodegenerative disorder Alzheimer bacterial hydrolase ortholog.

O-GlcNAcylation is a post-translational modification of tau understood to lower the speed and yield of its aggregation, a pathol. hallmark of Alzheimer’s disease (AD). O-GlcNAcase (OGA) is the only enzyme that removes O-linked N-acetyl-D-glucosamine (O-GlcNAc) from target proteins. Therefore, inhibition of OGA represents a potential approach for the treatment of AD by preserving the O-GlcNAcylated tau protein. Herein, we report the multifactorial optimization of high-throughput screening hit 8 to a potent, metabolically stable, and orally bioavailable diazaspirononane OGA inhibitor (+)-56. The human OGA X-ray crystal structure has been recently solved, but bacterial hydrolases are still widely used as structural homologues. For the first time, we reveal how a nonsaccharide series of inhibitors binds bacterial OGA and discuss the suitability of two different bacterial orthologues as surrogates for human OGA. These breakthroughs enabled structure-activity relationships to be understood and provided context and boundaries for the optimization of druglike properties.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Recommanded Product: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Sekioka, Ryuichi published the artcileDiscovery of N-ethylpyridine-2-carboxamide derivatives as a novel scaffold for orally active γ-secretase modulators, Name: 4-(1,2,4-Triazol-1-yl)benzyl Alcohol, the main research area is Alzheimer’s disease gamma secretase modulator myloid beta peptide; Alzheimer’s disease; Amyloid-beta peptide; Cytochrome P450 3A4; Gamma-secretase modulator.

Gamma-secretase modulators (GSMs) are promising disease-modifying drugs for Alzheimer’s disease because they can selectively decrease pathogenic amyloid-β42 (Aβ42) levels. Here we report the discovery of orally active N-ethylpyridine-2-carboxamide derivatives as GSMs. The isoindolinone moiety of 5-[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]-2-ethyl-2,3-dihydro-1H-isoindol-1-one hydrogen chloride (1a) was replaced with a picolinamide moiety. Optimization of the benzyl group significantly improved GSM activity and mouse microsomal stability. 5-{8-[([1,1′-Biphenyl]-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-N-ethylpyridine-2-carboxamide hydrogen chloride (1v) potently reduced Aβ42 levels with an IC50 value of 0.091μM in cultured cells without inhibiting CYP3A4. Moreover, 1v demonstrated a sustained pharmacokinetic profile and significantly reduced brain Aβ42 levels in mice.

Bioorganic & Medicinal Chemistry published new progress about Alzheimer disease. 143426-50-0 belongs to class triazoles, name is 4-(1,2,4-Triazol-1-yl)benzyl Alcohol, and the molecular formula is C9H9N3O, Name: 4-(1,2,4-Triazol-1-yl)benzyl Alcohol.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Wang, Shuai published the artcileDiscovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway, Synthetic Route of 24415-66-5, the main research area is triazolopyrimidinylamino diarylpropenone preparation antitumor activity SAR; 1,2,4]triazolo[1,5-a]pyrimidines; Apoptosis; Autophagy; Gastric cancer; Mitochondrial pathway.

A novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compoundsI [R1 = benzyl, 4-fluorobenzyl, 4-chlorobenzyl, etc.; R2 = Me, Et, Ph; R3 = H, Me] and II [R4 = Ph, (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl), (4-(3-(5-bromo-2-pyridyl)prop-2-enoyl)phenyl), etc.] were synthesized and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl), (4-(3-(5-bromo-2-pyridyl)prop-2-enoyl)phenyl)] inhibited gastric cancer cells at micromolar level. Compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] caused G2/M arrest and induced mitochondria-dependent apoptosis in MGC-803 and SGC-7901. However, inhibiting apoptosis pathway cannot prevent the inhibitory activity of compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] against gastric cancer cell. To our surprising, ROS level was increased by compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] and elevation of ROS could be rescued by NAC. In accordance with that, NAC absolutely prevented the anti-proliferation efficacy of compound 4o. We further found that autophagy inhibitor CQ rather than 3-MA partially reversed inhibitory activity of compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] in MGC-803 cells. Taken together, compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Synthetic Route of 24415-66-5.

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics