Day: November 10, 2022

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

Chowdhury, Arindrajit published the artcileConfined rapid thermolysis/FTIR/ToF studies of methyl-amino-triazolium-based energetic ionic liquids, HPLC of Formula: 39602-93-2, the main research area is methyl amino triazolium energetic ionic liquid confined rapid thermolysis.

Thermal decomposition of the energetic ionic liquids 1-methyl-4-amino-1,2,4-triazolium iodide (Me4ATI), 1-methyl-4-amino-1,2,4-triazolium nitrate (Me4ATN), 1-amino-3-methyl-1,2,3-triazolium iodide (Me1ATI), and 1-amino-3-methyl-1,2,3-triazolium nitrate (Me1ATN) was studied by confined rapid thermolysis. Sub-milligram quantities of the compounds were subjected to decomposition under isothermal conditions achieved by initially heating the sample at rates of approx. 2000 K/s. The products formed by decomposition under the afore-mentioned conditions were sampled by rapid scan FTIR spectroscopy and time-of-flight mass spectrometry. Decomposition studies involving the iodide salts were carried out around 270-290°C, whereas the nitrate salts were subjected to 320-340 °C. The amino group was found to be involved in the initiation reaction, forming copious quantities of ammonia from the iodide compounds and, N2O and H2O from the nitrate compounds The extent of decomposition of the triazole ring was minimal at the considered temperatures

Thermochimica Acta published new progress about Ionic liquids. 39602-93-2 belongs to class triazoles, name is 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, and the molecular formula is C3H7IN4, HPLC of Formula: 39602-93-2.

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

Drake, Gregory published the artcile(1R)-4-amino-1,2,4-triazolium salts: New families of ionic liquids, Name: 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, the main research area is amino triazolium bromide nitrate preparation ionic liquid.

New classes of ionic liquids based upon the halide and nitrate salts of 1-alkyl substituted-4-amino-1,2,4-triazolium cations (R = Me, decyl, iso-Pr, allyl, and methylcyclopropyl) have been synthesized, characterized by vibrational spectra, multinuclear NMR, elemental anal., and DSC studies. Single crystal x-ray diffraction studies were carried out on 1-isopropyl-4-amino-1,2,4-triazolium bromide, 1-ethyl-4-amino-1,2,4-triazolium bromide, 1-propyl-4-amino-1,2,4-triazolium bromide, 1-hexyl-4-amino-1,2,4-triazolium bromide, and 1-heptyl-4-amino-1,2,4-triazolium bromide, as well as 1-isopropyl-4-amino-1,2,4-triazolium nitrate and 1-methylcyclopropyl-4-amino-1,2,4-triazolium nitrate. The details of similarities, differences, and the effects of strong hydrogen bonding in the all of the structures will be discussed.

ACS Symposium Series published new progress about Ionic liquids. 39602-93-2 belongs to class triazoles, name is 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, and the molecular formula is C3H7IN4, Name: 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide.

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

Tao, Guo-Hong published the artcileEnergetic ionic liquids based on lanthanide nitrate complex anions, SDS of cas: 39602-93-2, the main research area is lanthanide nitrate energetic ionic liquid preparation thermolysis enthalpy structure; safety energetic ionic liquid rare earth nitrate potential propellant.

Energetic ionic liquids based on anionic lanthanide nitrate complexes Cat+3[Ln(NO3)6]3-, where Cat+ is guanidinium, 4-aminotriazolium, 4-amino-1-methyltriazolium, 4-amino-1-ethyltriazolium, 4-amino-1-butyltriazolium, 1,5-diaminotetrazolium, and 1,5-diamino-4-methyltetrazolium, were prepared The hexanitratolanthanate (-cerate) salts with the last two cations, which are the 1st CO-balanced energetic ionic liquids that are stable to hydrolysis and air, have impact sensitivities of ∼27 J. These ionic liquids were obtained by an environmentally friendly, simple method using nitrate-containing precursors. All salts were fully characterized by IR and NMR spectroscopy, elemental anal., and determination of thermal stability, phase behavior, d., and H2O content. According to theor. calculations, these new compounds have potential as propellants.

Chemistry – A European Journal published new progress about Explosibility. 39602-93-2 belongs to class triazoles, name is 4-Amino-1-methyl-4H-1,2,4-triazol-1-ium iodide, and the molecular formula is C3H7IN4, SDS of cas: 39602-93-2.

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

Kannan, Murugan published the artcileSynthesis and in vitro evaluation of novel 8-aminoquinoline-pyrazolopyrimidine hybrids as potent antimalarial agents, Category: triazoles, the main research area is aminoquinoline pyrazolopyrimidine hybrid preparation SAR antimalarial activity; 8-Aminoquinoline; Hybridization; Plasmodium falciparum; Pyrazolopyrimidine; Structure activity relationship.

In the search of novel chemotherapeutic agents for emerging drug resistant parasites, the hybridization approaches have successfully emerged as an efficient tool in malarial chemotherapy. Herein, a rational design and synthesis of novel 8-aminoquinoline and pyrazolopyrimidine hybrids, e.g. I, and their antimalarial activity against wild type Plasmodium falciparum (Pf_NF54) and resistant strain (Pf_K1) is reported. The medicinal chem. approach to expand the scope of this series resulted in an identification of potent compounds with nanomolar potency (best IC50 5-10 nM). Systematic structure activity relationship (SAR) studies revealed that pyrazolopyrimidine and 8-aminoquinoline ring are essential for achieving good P. falciparum potency. The docking study revealed that the compound I can retain some of the critical interactions within pfDHODH drug target.

Bioorganic & Medicinal Chemistry Letters published new progress about Antimalarials. 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

Marwaha, Alka published the artcileBioisosteric Transformations and Permutations in the Triazolopyrimidine Scaffold To Identify the Minimum Pharmacophore Required for Inhibitory Activity against Plasmodium falciparum Dihydroorotate Dehydrogenase, Application of 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is triazolopyrimidine preparation Plasmodium dihydroorotate dehydrogenase inhibitor SAR.

Plasmodium falciparum causes approx. 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase that inhibit parasite in vitro growth with similar activity. Lead optimization of this series led to the recent identification of a preclin. candidate, showing good activity against P. falciparum in mice. As part of a backup program around this scaffold, we explored heteroatom rearrangement and substitution in the triazolopyrimidine ring and have identified several other ring configurations that are active as PfDHODH inhibitors. The imidazo[1,2-a]pyrimidines were shown to bind somewhat more potently than the triazolopyrimidines depending on the nature of the amino aniline substitution. DSM151, the best candidate in this series, binds with 4-fold better affinity (PfDHODH IC50 = 0.077 μM) than the equivalent triazolopyrimidine and suppresses parasites in vivo in the Plasmodium berghei model.

Journal of Medicinal Chemistry published new progress about Antimalarials. 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 of 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine.

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

Gujjar, Ramesh published the artcileLead Optimization of Aryl and Aralkyl Amine-Based Triazolopyrimidine Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Antimalarial Activity in Mice, Formula: C6H5ClN4, the main research area is aryl aralkyl amine triazolo pyrimidine preparation malaria; Plasmodium falciparum dihydroorotate dehydrogenase with antimalarial.

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-CF3-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.

Journal of Medicinal Chemistry published new progress about Antimalarials. 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, Formula: C6H5ClN4.

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

Boechat, Nubia published the artcileNew trifluoromethyl triazolopyrimidines as anti-Plasmodium falciparum agents, Formula: C6H5ClN4, the main research area is trifluoromethyl triazolopyrimidine preparation antimalarial SAR.

According to the World Health Organization, half of the World’s population, approx. 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2-(trifluoromethyl)[1,2,4]triazolo[1,5-α]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF3 group substituted at the 2-position of the [1,2,4]triazolo[1,5-α]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. According to docking simulations, the synthesized compounds are able to interact with P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-α]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC50 values ranging from 0.023 to 20 μM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478.

Molecules published new progress about Antimalarials. 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, Formula: C6H5ClN4.

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

Gujjar, Ramesh published the artcileIdentification of a Metabolically Stable Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Antimalarial Activity in Mice, COA of Formula: C6H5ClN4, the main research area is metabolically stable triazolopyrimidine derivative preparation dihydroorotate dehydrogenase malaria.

Plasmodium falciparum causes 1-2 million deaths annually. Yet current drug therapies are compromised by resistance. We previously described potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase (PfDHODH) that inhibited parasite growth in vitro; however, they showed no activity in vivo. Here we show that lack of efficacy against P. berghei in mice resulted from a combination of poor plasma exposure and reduced potency against P. berghei DHODH. For compounds containing naphthyl (DSM1) or anthracenyl (DSM2), plasma exposure was reduced upon repeated dosing. Phenyl-substituted triazolopyrimidines were synthesized leading to identification of analogs with low predicted metabolism in human liver microsomes and which showed prolonged exposure in mice. Compound 21 (DSM74), containing p-trifluoromethylphenyl, suppressed growth of P. berghei in mice after oral administration. This study provides the first proof of concept that DHODH inhibitors can suppress Plasmodium growth in vivo, validating DHODH as a new target for antimalarial chemotherapy.

Journal of Medicinal Chemistry published new progress about Antimalarials. 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

Hameed P, Shahul published the artcileAminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents, Category: triazoles, the main research area is aminoazabenzimidazole preparation SAR antimalarial Plasmodium.

Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chem. effort. Structure-activity relation studies followed by pharmacokinetics optimization resulted in the identification of (I) as an attractive lead with good oral bioavailability. Compound I was efficacious (ED90 of 28.6 mg·kg-1) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chem. class.

Journal of Medicinal Chemistry published new progress about Antimalarials. 502546-41-0 belongs to class triazoles, name is 5-Cyclopropyl-4H-1,2,4-triazol-3-amine, and the molecular formula is C5H8N4, Category: triazoles.

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