Tag: M.W=150-200

Artico, M. published the artcileAromatic hydrazides as specific inhibitors of bovine serum amine oxidase, Quality Control of 143426-50-0, the main research area is aromatic hydrazide preparation amine oxidase inhibitor; structure activity hydrazide oxidase inhibitor.

New hydrazides were synthesized in search for specific inhibitors of bovine serum amine oxidase: a series of benzoic and phenylacetic acid hydrazides containing the 1H-imidazol-1-yl or the 1H-imidazol-1-ylmethyl group as as o-, m-, or p-substituent in the Ph ring; an analogous series of p-substituted phenylhydrazides with a 5 or 6-membered heterocyclic ring substituent, and a series of similar phenylpropionic hydrazides. The longer and more flexible phenylacetic hydrazides, and to a somewhat lesser extent the phenylpropionic ones, were better specific inhibitors of bovine serum amine oxidase than the benzoic hydrazides, which were also bound by the enzyme with high affinity, but at a slow rate. Derivatives with p- and m-substituents were more reactive than the o-substituted ones. The chem. nature of the substituent was less important than its position in the Ph ring and the presence of methylene spacers. These data point to the presence of a hydrophobic site at short distance from the protein carbonyl cofactor, so that simultaneous interaction of the 2 ends of the inhibitor mol. can occur at the 2 sites. The presence of the hydrophobic site was confirmed by the capability of some mols. deprived of the hydrazidic group to act as mild inhibitors. All hydrazides were less reactive by 2-3 orders of magnitude towards pig kidney diamine oxidase and FAD-dependent monoamine oxidase from rat brain mitochondria, while the other compounds showed similar inhibition power against all proteins. The specificity for the bovine enzyme seems therefore to be related to the concerted action of the 2 moieties of the inhibitor mol.

European Journal of Medicinal Chemistry published new progress about aromatic hydrazide preparation amine oxidase inhibitor; structure activity hydrazide oxidase inhibitor. 143426-50-0 belongs to class triazoles, name is 4-(1,2,4-Triazol-1-yl)benzyl Alcohol, and the molecular formula is C9H9N3O, Quality Control of 143426-50-0.

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

Okabe, Takayuki published the artcileSyntheses of triazolopyrimidine derivatives from amitrole and their biological activity, Quality Control of 24415-66-5, the main research area is triazolopyrimidine synthesis amitrole fungicide; herbicide triazolopyrimidine synthesis amitrole.

Amitrole (3-amino-1,2,4-triazole) (I) [61-82-5] was condensed with active methylene ketones such as Et cyanoacetate, acetylacetone, ethyl acetoacetate to give the corresponding 7-amino-5-hydroxy-s-triazolo[1,5-a]pyrimidine [35186-69-7], 5,7-dimethyl-s-triazolo[1,5-a]pyrimidine [7681-99-4], and 7-hydroxy-5-methyl-s-triazolo[1,5-a]pyrimidine (II) [2503-56-2]; from II some 5-methyl-7-substituted-s-triazolopyrimidines were synthesized and tested for herbicidal and fungicidal activity. 7-Chloro-5-methyl-s-triazolo[1,5-a]pyrimidine (III) [24415-66-5] synthesized from II plus POCl3, as well as 5-methyl-7-thiocyano-s-triazolo[1,5-a]pyrimidine (IV) [35186-71-1] prepared from III plus NH4SCN actively inhibited spore germination of Ophiobolus miyabeanus. IV showed antibiotic effects on Bacillus subtilis, Pellicularia filamentosa, [Rhizoctonia solani], and Phytophthora infestans and was herbicidally active on Atriplex gmelini, but showed no growth regulatory activity on rice.

Gakugei Zasshi – Kyushu Daigaku Nogakubu published new progress about Fungicides. 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, Quality Control of 24415-66-5.

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

Kawaguchi, Mitsuyasu published the artcileDevelopment of an ENPP1 Fluorescence Probe for Inhibitor Screening, Cellular Imaging, and Prognostic Assessment of Malignant Breast Cancer, Name: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is ENPP1 fluorescence probe inhibitor screening imaging prognostic breast cancer.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that is involved in bone metabolism and insulin resistance, hydrolyzes 2′,3′-cGAMP (a STING ligand that promotes innate immunity), and is associated with cancer stemness in breast cancers and glioblastoma. Therefore, ENPP1 is considered a candidate therapeutic target and/or biomarker for early diagnosis of malignant tumors. In this study, we designed and synthesized a sensitive ENPP1 fluorescence probe, Tokyo Green (TG) mAMP. We used it to screen a chem. library for non-phosphate ENPP1 inhibitors. Structural optimization of a selected hit afforded a potent and specific ENPP1 inhibitor. We further found that ENPP1 mRNA expression in tissue samples from patients with triple-neg. breast cancer was significantly inversely related to recurrence-free survival (RFS) and overall survival (OS), and TG-mAMP assay revealed a significant difference in ENPP1 activity between ENPP1 high-expressing and ENPP1 low-expressing samples. Our results suggest that TG-mAMP assay might be a rapid and inexpensive tool for predicting the prognosis of patients with malignant breast cancers.

Journal of Medicinal Chemistry published new progress about Cancer diagnosis. 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

Phillips, Margaret A. published the artcileTriazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitors with Potent and Selective Activity against the Malaria Parasite Plasmodium falciparum, Recommanded Product: 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, the main research area is triazolopyrimidine preparation crystal structure dihydroorotate dehydrogenase inhibitor antimalarial agent; triazolo pyrimidine preparation dihydroorotate dehydrogenase inhibitor antimalarial Plasmodium falciparum.

A Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitor I that is potent (KI = 15 nM) and species-selective (>5000-fold over the human enzyme) was identified by high-throughput screening. The substituted triazolopyrimidine and its structural analogs were produced by an inexpensive three-step synthesis, and the series showed good association between PfDHODH inhibition and parasite toxicity. This study has identified the first nanomolar PfDHODH inhibitor with potent antimalarial activity in whole cells (EC50 = 79 nM).

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, 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

Singh, Anju published the artcileQuinoline carboxamide core moiety-based compounds inhibit P. falciparum falcipain-2: Design, synthesis and antimalarial efficacy studies, Computed Properties of 24415-66-5, the main research area is Plasmodium falcipain quinoline carboxamide based compound antimalarial; Drug development; Falcipain-2 (FP2); Malaria; P. falciparum; Quinoline carboxamide.

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 Hb degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated mol. 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 2.64μM, resp. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphol. 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.

Bioorganic 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, Computed Properties of 24415-66-5.

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

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

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

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