Tag: 100-200

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

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

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

Biodegradation of bisphenol a by Sphingobium sp. YC-JY1 and the essential role of cytochrome P450 monooxygenase was written by Jia, Yang;Eltoukhy, Adel;Wang, Junhuan;Li, Xianjun;Hlaing, Thet Su;Aung, Mar Mar;Nwe, May Thet;Lamraoui, Imane;Yan, Yanchun. And the article was included in International Journal of Molecular Sciences in 2020.Name: 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

Bisphenol A (BPA) is a widespread pollutant threatening the ecosystem and human health. An effective BPA degrader YC-JY1 was isolated and identified as Sphingobium sp. The optimal temperature and pH for the degradation of BPA by strain YC-JY1 were 30°C and 6.5, resp. The biodegradation pathway was proposed based on the identification of the metabolites. The addition of cytochrome P 450 (CYP) inhibitor 1-aminobenzotriazole significantly decreased the degradation of BPA by Sphingobium sp. YC-JY1. Escherichia coli BL21 (DE3) cells harboring pET28a-bisdAB achieved the ability to degrade BPA. The bisdB gene knockout strain YC-JY1ΔbisdB was unable to degrade BPA indicating that P 450 bisdB was an essential initiator of BPA metabolism in strain YC-JY1. For BPA polluted soil remediation, strain YC-JY1 considerably stimulated biodegradation of BPA associated with the soil microbial community. These results point out that strain YC-JY1 is a promising microbe for BPA removal and possesses great application potential. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Name: 1H-Benzo[d][1,2,3]triazol-1-amine).

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.Name: 1H-Benzo[d][1,2,3]triazol-1-amine

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

Synthesis of ¹⁸F-difluoromethylarenes using arylboronic acids, ethyl bromofluoroacetate and [¹⁸F]fluoride was written by Sap, Jeroen B. I.;Wilson, Thomas C.;Kee, Choon Wee;Straathof, Natan J. W.;am Ende, Christopher W.;Mukherjee, Paramita;Zhang, Lei;Genicot, Christophe;Gouverneur, Veronique. And the article was included in Chemical Science in 2019.HPLC of Formula: 179056-04-3 This article mentions the following:

Herein, the radiosynthesis of ¹⁸F-difluoromethylarenes RCHF¹⁸F (R = 4-C₂H₅, 4-OC₆H₅, 3,5-CH₃, etc.) via the assembly of three components, a boron reagent, Et bromofluoroacetate, and cyclotron-produced non-carrier added [¹⁸F]fluoride was reported. The two key steps are a copper-catalyzed cross-coupling reaction, and a Mn-mediated ¹⁸F-fluorodecarboxylation. In the experiment, the researchers used many compounds, for example, 4-(2H-1,2,3-Triazol-2-yl)benzaldehyde (cas: 179056-04-3HPLC of Formula: 179056-04-3).

4-(2H-1,2,3-Triazol-2-yl)benzaldehyde (cas: 179056-04-3) 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.HPLC of Formula: 179056-04-3

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

Toxicological role of an acyl glucuronide metabolite in diclofenac-induced acute liver injury in mice was written by Oda, Shingo;Shirai, Yuji;Akai, Sho;Nakajima, Akira;Tsuneyama, Koichi;Yokoi, Tsuyoshi. And the article was included in Journal of Applied Toxicology in 2017.Reference of 1614-12-6 This article mentions the following:

The acyl glucuronide (AG) metabolites of carboxylic acid-containing drugs are potentially chem. reactive and are suggested to be implicated in toxicity, including hepatotoxicity, nephrotoxicity and drug hypersensitivity reactions. However, it remains unknown whether AG formation is related to toxicity in vivo. In this study, we sought to determine whether AG is involved in the pathogenesis of liver injury using a mouse model of diclofenac (DIC)-induced liver injury. Mice that were administered DIC alone exhibited significantly increased plasma alanine aminotransferase levels, whereas mice that were pretreated with the UDP-glucuronosyltransferase inhibitor (-)-borneol (BOR) exhibited suppressed alanine aminotransferase levels at 3 and 6 h after DIC administration although not significant at 12 h. The plasma DIC-AG concentrations were significantly lower in BOR- and DIC-treated mice than in mice treated with DIC alone. The mRNA expression levels of chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2 and the neutrophil marker CD11b were reduced in the livers of mice that had been pretreated with BOR compared to those that had been administered DIC alone, whereas mRNA expression of the macrophage marker F4/80 was not altered. An immunohistochem. anal. at 12 h samples revealed that the numbers of myeloperoxidase- and lymphocyte antigen 6 complex-pos. cells that infiltrated the liver were significantly reduced in BOR- and DIC-treated mice compared to mice that were treated with DIC alone. These results indicate that DIC-AG is partly involved in the pathogenesis of DIC-induced acute liver injury in mice by activating innate immunity and neutrophils. Copyright © 2016 John Wiley & Sons, Ltd. 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 exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within the ring. 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.Reference of 1614-12-6

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

Identification of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor was written by Kung, Daniel W.;Coffey, Steven B.;Jones, Ryan M.;Cabral, Shawn;Jiao, Wenhua;Fichtner, Michael;Carpino, Philip A.;Rose, Colin R.;Hank, Richard F.;Lopaze, Michael G.;Swartz, Roger;Chen, Hou;Hendsch, Zachary;Posner, Bruce;Wielis, Christopher F.;Manning, Brian;Dubins, Jeffrey;Stock, Ingrid A.;Varma, Sam;Campbell, Mary;DeBartola, Demetria;Kosa-Maines, Rachel;Steyn, Stefanus J.;McClure, Kim F.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.Synthetic Route of C9H7N3O This article mentions the following:

The discovery of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor is described. The characterization and redressing of the issues associated with these compounds is detailed. An efficient three-step synthesis and a binding assay were relied upon as the primary means of rapidly improving potency and ADMET properties for this class of inverse agonist compounds Compound 10n bearing distributed polarity in the form of an imidazo-thiazole acetamide and a Ph triazole is a unit lower in log P and has significantly improved binding affinity compared to the hit mol. 10a, providing support for further optimization of this series of compounds In the experiment, the researchers used many compounds, for example, 4-(2H-1,2,3-Triazol-2-yl)benzaldehyde (cas: 179056-04-3Synthetic Route of C9H7N3O).

4-(2H-1,2,3-Triazol-2-yl)benzaldehyde (cas: 179056-04-3) 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. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Synthetic Route of C9H7N3O

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

Structural stabilization of a metal-organic framework for gas sorption investigation was written by Gao, Qiang;Zhao, Xiao-Lin;Chang, Ze;Xu, Jian;Bu, Xian-He. And the article was included in Dalton Transactions in 2016.Recommanded Product: 157069-48-2 This article mentions the following:

By inserting a ligand into a reported metal-organic framework (Co-MOF1), the reformed aggregation of triangle grids, [Co₃(μ₃-O)(cpt)₃tpt·NO₃] (Co-MOF1-tpt) (Hcpt = 4-(4′-carboxyphenyl)-1,2,4-triazole, tpt = tri(4-pyridyl)-1,3,5-triazine), shows enhanced stability. In addition, owing to its structural characteristic, the Co-MOF1-tpt also reveals a certain CO₂ storage ability and CO₂/CH₄ adsorption selectivity as expected. 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. 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. 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

Whole-cell amperometric biosensor for screening of cytochrome P450 inhibitors was written by Yoetz-Kopelman, Tal;Porat-Ophir, Carmit;Shacham-Diamand, Yosi;Freeman, Amihay. And the article was included in Sensors and Actuators, B: Chemical in 2016.Name: 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

A fast and cost-effective whole-cell electrochem. biosensor aiming at early-stage screening of potential inhibitors of cytochrome P 450 is proposed and its feasibility demonstrated. Sensing is performed by monitoring the decrease in the electrochem. signal generated by the oxidation of the product of the enzymic reaction of cytochrome P 450 BM3 expressed in E. coli cells. The system is self-maintained and does not require enzyme purification or external addition of NADPH or other cofactors. Measurements were performed simultaneously at eight chips at low pos. potential of 100 mV vs. Ag/AgCl under continuous stirring. Kinetic anal. of aniline determination by the whole-cell system was performed and the concentration of aniline for the inhibition studies was selected accordingly. Three known inhibitors – imidazole, metyrapone and 1-aminobenzotriazole (ABT) – were tested and their inhibition profiles characterized. Imidazole was found to be the most potent inhibitor of the three. To the best of our knowledge, the system developed enables for the first time rapid and cheap cytochrome P 450 inhibitors detection by a disposable whole-cell electrochem. chip, combined with the advantages of a whole-cell system, without neither enzyme purification nor NADPH addition Furthermore, the system developed also provides capability of performing aniline detection e.g. for environmental monitoring, by means of electrochem. biosensing. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Name: 1H-Benzo[d][1,2,3]triazol-1-amine).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within the ring. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Name: 1H-Benzo[d][1,2,3]triazol-1-amine

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

5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors was written by Ai, Teng;Wilson, Daniel J.;More, Swati S.;Xie, Jiashu;Chen, Liqiang. And the article was included in Journal of Medicinal Chemistry in 2016.Recommanded Product: 4-(4H-1,2,4-Triazol-4-yl)benzoic acid This article mentions the following:

Derived from the previously reported human sirtuin 2 (SIRT2) inhibitors that were based on a 5-aminonaphthalen-1-yloxy nicotinamide core structure, 5-((3-amidobenzyl)oxy)nicotinamides offered excellent activity against SIRT2 and high isoenzyme selectivity over SIRT1 and SIRT3. Selected compounds also exhibited generally favorable in vitro absorption, distribution, metabolism, and excretion properties. Kinetic studies revealed that a representative SIRT2 inhibitor acted competitively against both NAD⁺ and the peptide substrate, an inhibitory modality that was supported by the computational study. More importantly, two selected compounds I and II exhibited significant protection against α-synuclein aggregation-induced cytotoxicity in SH-SY5Y cells. Therefore, 5-((3-amidobenzyl)oxy)nicotinamides represent a new class of SIRT2 inhibitors that are attractive candidates for further lead optimization in the continued effort to explore selective inhibition of SIRT2 as a potential therapy for Parkinson’s disease. 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: 4-(4H-1,2,4-Triazol-4-yl)benzoic acid).

4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2) belongs to triazole derivatives. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within the ring. 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.Recommanded Product: 4-(4H-1,2,4-Triazol-4-yl)benzoic acid

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