Month: January 2023

Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor against Malignant Brain Tumors was written by Tsang, Jonathan E.;Urner, Lorenz M.;Kim, Gyudong;Chow, Kingsley;Baufeld, Lynn;Faull, Kym;Cloughesy, Timothy F.;Clark, Peter M.;Jung, Michael E.;Nathanson, David A.. And the article was included in ACS Medicinal Chemistry Letters in 2020.Reference of 1614-12-6 This article mentions the following:

The epidermal growth factor receptor (EGFR) is genetically altered in nearly 60% of glioblastoma tumors; however, tyrosine kinase inhibitors (TKIs) against EGFR have failed to show efficacy for patients with these lethal brain tumors. This failure is attributed to the inability of clin. tested EGFR TKIs to cross the blood-brain barrier (BBB) and achieve adequate pharmacol. levels to inhibit various oncogenic forms of EGFR that drive glioblastoma. Through SAR anal., we developed compound 5 (JCN037)(I) from an anilinoquinazoline scaffold by ring fusion of the 6,7-dialkoxy groups to reduce the number of rotatable bonds and polar surface area and by introduction of an ortho-fluorine and meta-bromine on the aniline ring for improved potency and BBB penetration. Relative to the conventional EGFR TKIs erlotinib and lapatinib, JCN037 displayed potent activity against EGFR amplified/mutant patient-derived cell cultures, significant BBB penetration (2:1 brain-to-plasma ratio), and superior efficacy in an EGFR-driven orthotopic glioblastoma xenograft model. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Reference of 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, triadimenol, myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.Reference of 1614-12-6

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

Efficacy of novel pyrazolone phosphodiesterase inhibitors in experimental mouse models of Trypanosoma cruzi was written by Siciliano de Araujo, Julianna;da Silva, Cristiane Franca;da Gama Jaen Batista, Denise;Nefertiti, Aline;Ferreira de Almeida Fiuza, Ludmila;Fonseca-Berzal, Cristina Rosa;da Silva, Patricia Bernardino;Batista, Marcos Meuser;Sijm, Maarten;Kalejaiye, Titilola D.;de Koning, Harry P.;Maes, Louis;Sterk, Geert Jan;Leurs, Rob;de Nazare Correia Soeiro, Maria. And the article was included in Antimicrobial Agents and Chemotherapy in 2020.Recommanded Product: 1614-12-6 This article mentions the following:

Pyrazolones are heterocyclic compounds with interesting biol. properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cAMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan Trypanosoma cruzi, the etiol. agent of Chagas disease (CD), a major neglected tropical disease. In vitro phenotypic screening identified a 4-bromophenyl-dihydropyrazole dimer as an anti-T. cruzi hit and 17 novel pyrazolone analogs with variations on the Ph ring were investigated in a panel of phenotypic laboratory models. Potent activity against the intracellular forms (Tulahuen and Y strains) was obtained with 50% effective concentration (EC₅₀) values within the 0.17 to 3.3μM range. Although most were not active against bloodstream trypomastigotes, an altered morphol. and loss of infectivity were observed Pretreatment of the mammalian host cells with pyrazolones did not interfere with infection and proliferation, showing that the drug activity was not the result of changes to host cell metabolism The pyrazolone NPD-227 increased the intracellular cAMP levels and was able to sterilize T. cruzi-infected cell cultures. Thus, due to its high potency and selectivity in vitro, and its additive interaction with benznidazole (Bz), NPD-227 was next assessed in the acute mouse model. Oral dosing for 5 days of NPD-227 at 10 mg/kg + Bz at 10 mg/kg not only reduced parasitemia (>87%) but also protected against mortality (>83% survival), hence demonstrating superiority to the monotherapy schemes. These data support these pyrazolone mols. as potential novel therapeutic alternatives for Chagas disease. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Recommanded Product: 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles consist of a five-membered ring containing three nitrogen atoms and are biologically active, especially as antifungal, antimicrobial and enzyme inhibitors. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Recommanded Product: 1614-12-6

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

Regioselective Oxo-Amination of Alkenes and Enol Ethers with N-Bromosuccinimide-Dimethyl Sulfoxide Combination: A Facile Synthesis of α-Amino-Ketones and Esters was written by Prasad, Pragati K.;Reddi, Rambabu N.;Sudalai, Arumugam. And the article was included in Organic Letters in 2016.Quality Control of Ethyl 1H-1,2,3-triazole-5-carboxylate This article mentions the following:

An unprecedented conversion of alkenes and enol ethers to the corresponding α-imido carbonyl compounds with excellent regioselectivity and yields has been developed. This oxo-amination process employs readily available N-bromosuccinimide (NBS) and secondary amines as N-sources and DMSO (DMSO) as the oxidant and also leads to the production of amino alcs. in a single step on reduction, thus broadening the scope of this operationally simple reaction. For the first time, the formation of reactive Me₂S⁺-O-Br species generated by the interaction of NBS with DMSO has been proven. In the experiment, the researchers used many compounds, for example, Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7Quality Control of Ethyl 1H-1,2,3-triazole-5-carboxylate).

Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA.Triazole heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Quality Control of Ethyl 1H-1,2,3-triazole-5-carboxylate

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

Co-ligand tuned pyrimidine-2-carboxylate Mn(II) complexes from a 2D 6³ layer to an interpenetrated srs-net was written by Sun, Rui;Gao, Su-Mei;Wang, Shao-Qiang;Song, Wei-Chao;Zhao, Jiong-Peng;Liu, Fu-Chen. And the article was included in Dalton Transactions in 2017.COA of Formula: C4H3N3O4 This article mentions the following:

A 6³ 2D layer complex [Mn₃Cl₃(L₃)]_n·H₂O (1) (L = pyrimidine-2-carboxylate) was obtained by assembling 2-cyanopyrimidine and manganese chloride, in which the L ligands were generated in situ. In 1 six-membered Mn rings were constructed from Mn^II ions and L ligands, which were connected to each other by double chloride anions affording a 2D layer. When the chloride anions in 1 were substituted partly by formate, [Mn₄Cl₃L₄(HCO₂)]_n (2) was obtained. In 2, the L ligands bridge Mn^II to give a 1D chain, which was further connected by the double chloride anions and Cl/formate bridges to form a two-fold interpenetrated srs-net. 2 Exhibits an obvious SHG response of ∼0.8 times that of KDP. Furthermore, 2 is an antiferromagnet with a field induced spin flop transition. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6COA of Formula: C4H3N3O4).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. However, triazoles are also useful in bioorthogonal chemistry, because the large number of nitrogen atoms causes triazoles to react similar to azides. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities.COA of Formula: C4H3N3O4

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

Edge-directed assembly of a 3D 2p-3d heterometallic metal-organic framework based on a cubic Co₈(TzDC)₁₂ cage was written by Tian, Dan;Liu, Sui-Jun;Chang, Ze;Zhang, Ying-Hui;Zhao, Jiong-Peng;Bu, Xian-He. And the article was included in CrystEngComm in 2013.Product Details of 4546-95-6 This article mentions the following:

A three-dimensional (3D) heterometallic metal-organic framework containing cubic-like cages, {[Co₃Na₆(TzDC)₄(H₂O)₆]·7H₂O}_n (1) (H₃TzDC = 1,2,3-triazole-4,5-dicarboxylic acid), was synthesized by the edge-directed self-assembly of TzDC^3-, Co²⁺ and Na⁺ ions. Crystal data reveals that one hydrous Co²⁺ cation is embedded in the central cavity of a cubic-like cage [Co₈(TzDC)₁₂]^20- with eight Co²⁺ cations as the corners and twelve TzDC^3- ligands as the edges. The cages are further bridged by Na⁺ ions to result in a 3-dimensional framework with pcu topol. Magnetic study indicates that besides the spin-orbit coupling of Co²⁺ ions, an antiferromagnetic exchange interaction was found to exist between the Co²⁺ ions in the Co₉ cluster of 1. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Product Details of 4546-95-6).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. However, triazoles are also useful in bioorthogonal chemistry, because the large number of nitrogen atoms causes triazoles to react similar to azides. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Product Details of 4546-95-6

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

Colorimetric Dual Sensors of Metal Ions Based on 1,2,3-Triazole-4,5-Dicarboxylic Acid-Functionalized Gold Nanoparticles was written by Mondal, Palash;Yarger, Jeffery L.. And the article was included in Journal of Physical Chemistry C in 2019.Product Details of 4546-95-6 This article mentions the following:

A simple, rapid, selective, and cost-effective colorimetric assay for Cr³⁺ and Eu³⁺ ion detection has been developed using functionalized gold nanoparticles. Gold nanoparticles (AuNPs) were prepared using HAuCl₄, where sodium citrate is a reducing agent as well as a capping agent, and then functionalized with 1,2,3-triazole-4,5-dicarboxylic acid (TADA). Fourier transform IR (FTIR) and Raman spectroscopies suggested that TADA was functionalized on the surface of AuNPs through the N atom of triazole. The TADA-functionalized gold nanoparticles (TADA@AuNPs) simultaneously detect Cr³⁺ and Eu³⁺ ions from aqueous solution and showed different responses to the two metal ions (Cr³⁺ and Eu³⁺) based on an aggregation-induced color change of AuNPs. They showed a color change from wine red to blue, which was easily detected by the naked eye, as well as by UV-visible and FTIR spectroscopies. The surface plasmon resonance absorbances of Cr³⁺ and Eu³⁺ are 633 and 671 nm, resp., when Cr³⁺ and Eu³⁺ react with TADA@AuNPs and showed good linearity with Cr³⁺ and Eu³⁺ concentrations with detection limits 5.89 nM and 4.30 μM, resp. (S/N = 3). The TADA@AuNPs showed excellent selectivity toward Cr³⁺ and Eu³⁺ compared to those of the 16 different metal ions. We had also tested the selectivity of TADA@AuNPs toward Eu³⁺ compared to that of the other 10 lanthanide systems. Optimal detection was achieved toward Cr³⁺ and Eu³⁺ ions in the pH range 4-10. In addition, TADA@AuNPs were applied to detect Cr³⁺ and Eu³⁺ ions from lake water showing low interference. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Product Details of 4546-95-6).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands. 1,2,3-Triazoles are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles.Product Details of 4546-95-6

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

A 3D-diamond-like metal-organic framework: Crystal structure, nonlinear optical effect and high thermal stability was written by Wang, Lihua;Ye, Yingxiang;Zhang, Liuqin;Chen, Qianhuo;Ma, Xiuling;Zhang, Zhangjing;Xiang, Shengchang. And the article was included in Inorganic Chemistry Communications in 2015.Recommanded Product: 157069-48-2 This article mentions the following:

A new metal-organic framework [Zn(cpt)(ATZ)]_n (1, HATZ = 5-amino-1H-tetrazol, Hcpt = 4-(4H-1,2,4-Triazol-4-yl)benzoic acid), has been solvothermally synthesized and structurally characterized by single crystal X-ray diffraction. Structural anal. shows that compound 1 is a three-dimensional (3D) framework with 3-fold interpenetrated diamond topol. where the Zn(II) centers are all 4-coordinated. Compound 1 exhibits high thermal stability up to 370 °C, and weak second-order nonlinear optical coefficient as ca. 0.13 times as that of potassium dihydrogen phosphate (KDP), and also displays blue photoluminescence at room temperature In the experiment, the researchers used many compounds, for example, 4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2Recommanded Product: 157069-48-2).

4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules.Recommanded Product: 157069-48-2

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

In Vitro Metabolism by Aldehyde Oxidase Leads to Poor Pharmacokinetic Profile in Rats for c-Met Inhibitor MET401 was written by Zhang, Jiang Wei;Deng, Hai Bing;Zhang, Chun Ye;Dai, Jing Quan;Li, Qian;Zheng, Qian Gang;Wan, Hui Xin;Yu, Hong Ping;He, Feng;Xu, Yao Chang;Zhao, Sylvia;Zhang, Ji Yue Jeff. And the article was included in European Journal of Drug Metabolism and Pharmacokinetics in 2019.COA of Formula: C6H6N4 This article mentions the following:

MET401 is a potent and selective c-Met inhibitor with a novel triazolopyrimidine scaffold. The aim of this study was to determine the pharmacokinetic profile of MET401 in preclin. species, and to identify the metabolic soft spot and enzyme involved, in order to help medicinal chemists to modify the compound to improve the pharmacokinetic profile. A metabolite identification study was performed in different liver fractions from various species. Chem. inhibition with selective cytochrome P 450 (CYP) and molybdenum hydroxylase inhibitors was carried out to identify the enzyme involved. The deuterium substitution strategy was adopted to reduce metabolism Pharmacokinetic studies were performed in rats to confirm the effect. Although M-2 is a minor metabolite in liver microsomal incubations, it became the predominant metabolite in incubations with liver S9, cytosol, hepatocytes and rat pharmacokinetic study. M-2 was synthesized enzymically and the structure was identified as a mono-oxidation on the triazolopyrimidine moiety. The M-2 formation was ascribed to aldehyde oxidase (AO)-mediated metabolism based on the following evidence-M-2 production was NADPH independent, pan-CYP inhibitor 1-aminobenzotriazole and xanthine oxidase inhibitor allopurinol did not inhibit M-2 formation, and AO inhibitors menadione and raloxifene inhibited M-2 formation. The deuterated analog MET763 demonstrated an improved pharmacokinetic profile with lower clearance, longer terminal half-life and double oral exposure compared with MET401 in rats. These results indicate that the main metabolic pathway of MET401 is AO-mediated metabolism, which leads to poor in vivo pharmacokinetic profiles in rodents. The deuterium substitution strategy could be used to reduce AO-mediated metabolism liability. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6COA of Formula: C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.COA of Formula: C6H6N4

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

Evaluation of the pharmacokinetic-pharmacodynamic relationship of praziquantel in the Schistosoma mansoni mouse model was written by Abla, Nada;Keiser, Jennifer;Vargas, Mireille;Reimers, Natalie;Haas, Helmut;Spangenberg, Thomas. And the article was included in PLoS Neglected Tropical Diseases in 2017.Computed Properties of C6H6N4 This article mentions the following:

After more than 40 years of use, Praziquantel (PZQ) still remains the drug of choice for the treatment of intestinal and urogenital schistosomiasis. Its anti-parasitic activity resides primarily in the (R)-enantiomer. Hitherto neither the mol. target nor the pharmacokinetic-pharmacodynamic relationship have been fully elucidated. Here we investigated the efficacy and pharmacokinetics of PZQ in the Schistosoma mansoni mouse model to determine the key factors that drive its efficacy. Dose-response studies with racemic PZQ with or without addition of an irreversible pan-cytochrome P 450 (CYP) inhibitor, 1-aminobenzotriazole (ABT), were performed. In addition, efficacy of PZQ in the presence of the CYP inducer, dexamethasone (DEX), was determined Plasma samples were obtained by tail vein bleeding at 4 time points. The (R)-PZQ levels were determined using a LC-MS/MS method. Non-compartmental pharmacokinetic anal. was performed using PKsolver. In addition, experiments using an enhanced in vitro assay were conducted. We found that the use of ABT increased (R)-PZQ plasma exposures in the systemic circulation by ∼10 to 20 fold but the latter were not predictive of efficacy. The use of DEX decreased plasma exposures of (R)-PZQ in the systemic circulation by ∼10 fold without reducing efficacy. We extrapolated the (R)-PZQ concentrations in mouse portal vein / mesenteric veins from the systemic exposures and found that a free exposure of (R)-PZQ of ∼ 20 μM*h in the portal vein was needed to obtain a worm burden reduction >60%. It is suggested that the high (R)-PZQ concentrations available before the hepatic first pass metabolism drive the efficacy against S. mansoni adult worms residing in the mesenteric veins. It is then possible that the current dosing regimen of 40 mg/kg in preventive chemotherapy programs may provide suboptimal concentrations in low-weight patients such as children, due to smaller total amounts of drug administered, and may consequently result in lower cure rates. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Computed Properties of C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Many triazoles are versatile, biologically active compounds commonly used as fungicides and plant retardants. 1,2,3-Triazoles are usually prepared following (3+2) cycloaddition protocols. A common technique for unsubstituted triazoles is the Huisgen azide-alkyne 1,3-dipolar cycloaddition: a azide and an alkyne react at high temperature to form a ring. However, the Huisgen strategy produces a mixture of isomers (typically 1,4- and 1,5-disubstituted) when used to produce substituted triazoles.Computed Properties of C6H6N4

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

Metabolic characterization of a potent natural neuroprotective agent dendrobine in vitro and in rats was written by Pan, Hong;Shi, Fu-guo;Fang, Chao;Shi, Jing-shan. And the article was included in Acta Pharmacologica Sinica in 2022.Formula: C6H6N4 This article mentions the following:

Dendrobine is the main sesquiterpene alkaloid of Dendrobium nobile Lindl, which exhibits potent neuroprotective activity. However, its metabolism and disposition are little known. In this study, we investigated the metabolic characteristics of dendrobine in vitro and in rats. The metabolic stability and temporal profile of metabolites formation of dendrobine were assayed in human/rat liver microsomal and S9 fractions. Dendrobine metabolites were separated and identified mainly by UPLC-Q/Orbitrap MS. After oral administration of dendrobine (50 mg/kg) to rats, the accumulative excretion rate of dendrobine in feces, urine, and bile was 0.27%, 0.52%, and 0.031%, resp., and low systematic exposure of dendrobine (AUC0-∞ = 629.2 ± 56.4 ng·h/mL) was observed We demonstrated that the elimination of dendrobine was very rapid in liver microsomal incubation (the in vitro elimination t1/2 in rat and human liver microsomes was 1.35 and 5.61 min, resp.). Dendrobine underwent rapid and extensive metabolism; cytochrome P 450, especially CYP3A4, CYP2B6, and CYP2C19, were mainly responsible for its metabolism Aldehyde dehydrogenase, alc. dehydrogenase and aldehyde oxidase were involved in the formation of carboxylic acid metabolites. By the aid of in-source fragmentation screening, hydrogen/deuterium exchange experiment, post-acquisition processing software, and available reference standards, 50 metabolites were identified and characterized in liver microsomal incubation and in rats. The major metabolic pathways of dendrobine were N-demethylation, N-oxidation, and dehydrogenation, followed by hydroxylation and glucuronidation. Collectively, the metabolic fate of dendrobine elucidated in this study not only yields benefits for its subsequent metabolism study but also facilitates to better understanding the mode of action of dendrobine and evaluating the pharmacol. efficiency of the high exposure metabolites. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Formula: C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities.Formula: C6H6N4

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