Category: 1614-12-6

Transport-metabolism interplay of atazanavir in rat hepatocytes was written by Nicolaie, Johan;De Bruyn, Tom;Thevelin, Louise;Augustijns, Patrick;Annaert, Pieter. And the article was included in Drug Metabolism & Disposition in 2016.Application of 1614-12-6 This article mentions the following:

The aim of this study was to explore the mechanisms governing the intra- to extracellular unbound concentration ratio (Kpu,u) for the HIV protease inhibitor atazanavir (ATV) in rat hepatocytes. We had previously proposed a new method to determine Kpu,u by using the unbound Km values from metabolism studies with suspended rat hepatocytes and rat liver microsomes. Following that method, we determined that the value of ATV Kpu,u was 0.32, indicating that ATV hepatocellular clearance is uptake rate-limited. This hypothesis was supported by the linear correlation between Kpu,u and active uptake clearance (P = 0.04; R²=0.82) in the presence of increasing concentrations of the uptake transport inhibitor losartan. Moreover, in contrast to an expected increase of Kpu,u upon inhibition of ATV metabolism, a decrease of Kpu,u was observed, suggesting an increased impact of sinusoidal efflux. In summary, involvement of active uptake transport does not guarantee high intracellular accumulation; however, it has a key role in regulating intracellular drug concentrations and drug metabolism These findings will help improve future in vitro-to-in vivo extrapolations and likewise physiol. based pharmacokinetic models. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Application of 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeApplication of 1614-12-6

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

Methoxsalen as an in vitro phenotyping tool in comparison with 1-aminobenzotriazole was written by Palacharla, Raghava Choudary;Molgara, Parusharamulu;Panthangi, Hanumanth Rao;Boggavarapu, Rajesh Kumar;Manoharan, Arun Kumar;Ponnamaneni, Ranjith Kumar;Ajjala, Devender Reddy;Nirogi, Ramakrishna. And the article was included in Xenobiotica in 2019.Category: triazoles This article mentions the following:

The objective is to evaluate methoxsalen as an in vitro phenotyping tool in comparison to ABT as a nonspecific inactivator of P 450 mediated metabolism The reversible inhibition of methoxsalen and ABT against the P 450, FMO, AO, MAO-A and -B, enzymes were evaluated using standard marker probe reactions. The time-dependent inhibition of P 450 enzymes was evaluated in human liver microsomes. CES1 activities were determined by monitoring the depletion of known substrate, the clopidogrel. The metabolism of P 450 substrates in the presence and absence of methoxsalen or ABT was evaluated in human liver microsomes. Methoxsalen is a direct inhibitor and inhibited the activities (>90%) of all enzymes at a concentration of 300μM except for CYP2C9. Methoxsalen is also a potent time-dependent inhibitor of all P 450 enzymes except for CYP2C19 (moderate) at a concentration of 300μM. Methoxsalen inhibited the metabolism of P 450 substrates in the pre-incubation mode. ABT is a potent TDI of several P 450 except for CYP2C19 (47%) and CYP2C9 (27%). The results indicate that methoxsalen is a potent pan P 450 inhibitor than ABT and can be a better tool in distinguishing P 450 mediated metabolism form non-P 450 metabolism in human liver microsomes. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Category: triazoles).

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. 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.Category: triazoles

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

CYP450-mediated mitochondrial ROS production involved in arecoline N-oxide-induced oxidative damage in liver cell lines was written by Wang, Tsu-Shing;Lin, Cheng-Ping;Chen, Yu-Pong;Chao, Mu-Rong;Li, Chien-Chun;Liu, Kai-Li. And the article was included in Environmental Toxicology in 2018.Application In Synthesis of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

IARC has classified the betel nut as a human environmental carcinogen. Previous studies have found that arecoline (AR) is the major alkaloid present in the saliva of betel quid chewers. Saliva contains a large content of AR which has been further shown to cause mutation of oral mucosa cells, resulting in oral cancer. Whereas, to date, there are only few studies reported the hepatotoxicity associated with arecoline and betel nut chewing. Therefore, the main purpose of this study was to determine the toxic effects of AR and its oxidative metabolite, arecoline N-oxide (ARNO), in normal liver cell lines. The cytotoxic, genotoxic, and mutagenic effects were detected by crystal violet staining, alk. comet assay, and Salmonella mutagenicity test, resp. Antioxidants, such as N-acetylcysteine, Trolox, and penicillamine, strongly protected liver cells from ARNO-induced DNA damage and ROS production Furthermore, co-treatment with Mito-TEMPO also effectively blocked ARNO-induced ROS production in liver cells. Besides antioxidants, co-treatment with 1-aminobenzotriazole and methimazole nearly completely suppressed ARNO-induced ROS production in liver cells. Our data suggest that arecoline ingested from the habit of chewing betel quid can be primarily oxidized to ARNO, thereby enhancing its toxicity through increased ROS production Collectively, our results provide novel cellular evidence for the pos. connection between habitual betel quid chewing and the risk for liver damage. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Application In Synthesis of 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 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. 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.Application In Synthesis of 1H-Benzo[d][1,2,3]triazol-1-amine

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

The 2-hydroxyiminostilbene metabolite of carbamazepine or the supernatant from incubation of hepatocytes with carbamazepine activates inflammasomes: implications for carbamazepine-induced hypersensitivity reactions was written by Kato, Ryuji;Ijiri, Yoshio;Hayashi, Tetsuya;Uetrecht, Jack. And the article was included in Drug Metabolism & Disposition in 2019.Computed Properties of C6H6N4 This article mentions the following:

In the present study, we investigated whether carbamazepine induces the release of DAMPs by using human hepatocarcinoma functional liver cell-4 (FLC-4) cells for bioactivation of carbamazepine. THP-1 cells, a human macrophage cell line, were used for detecting inflammasome activation. We found that increased caspase-1 activity and production of interleukin-1b by THP-1 cells were caused by the supernatant from the incubation of carbamazepine with FLC-4 cells. In the supernatant, heat shock protein 60 was significantly increased. In addition, 2-hydroxyiminostilbene, which is a metabolite of carbamazepine, activated inflammasomes. These results suggest that the reactive iminoquinone metabolite can directly activate inflammasomes or that stressed hepatocytes cause the release of DAMPs, which are responsible for inflammasome activation. The activation of inflammasomes may be an important step in the immune system activation by carbamazepine, which can lead to hypersensitivity reactions in some patients. 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. However, triazoles are also useful in bioorthogonal chemistry, because the large number of nitrogen atoms causes triazoles to react similar to azides. 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.Computed Properties of C6H6N4

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

Nonclinical pharmacokinetics, disposition, and drug-drug interaction potential of a novel D-amino acid peptide agonist of the calcium-sensing receptor AMG 416 (Etelcalcetide) was written by Subramanian, Raju;Zhu, Xiaochun;Kerr, Savannah J.;Esmay, Joel D.;Louie, Steven W.;Edson, Katheryne Z.;Walter, Sarah;Fitzsimmons, Michael;Wagner, Mylo;Soto, Marcus;Pham, Roger;Wilson, Sarah F.;Skiles, Gary L.. And the article was included in Drug Metabolism & Disposition in 2016.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

AMG 416 (etelcalcetide) is a novel synthetic peptide agonist of the calcium-sensing receptor composed of a linear chain of seven D-amino acids (referred to as the D-amino acid backbone) with a D-cysteine linked to an L-cysteine via a disulfide bond. AMG 416 contains four basic D-arginine residues and is a +4 charged peptide at physiol. pH with a mol. weight of 1048.3 Da. The pharmacokinetics (PK), disposition, and potential of AMG 416 to cause drug-drug interaction were investigated in nonclin. studies with two single ¹⁴C-labels placed either at a potentially metabolically labile acetyl position or on the D-alanine next to D-cysteine in the interior of the D-amino acid backbone. After i.v. dosing, the PK and disposition of AMG 416 were similar in male and female rats. Radioactivity rapidly distributed to most tissues in rats with intact kidneys, and renal elimination was the predominant clearance pathway. No strain-dependent differences were observed In bilaterally nephrectomized rats, minimal radioactivity (1.2%) was excreted via nonrenal pathways. Biotransformation occurred primarily via disulfide exchange with endogenous thiol-containing mols. in whole blood rather than metabolism by enzymes, such as proteases or cytochrome P450s; the D-amino acid backbone remained unaltered. A substantial proportion of the plasma radioactivity was covalently conjugated to albumin. AMG 416 presents a low risk for P 450 or transporter-mediated drug-drug interactions because it showed no interactions in vitro. These studies demonstrated a ¹⁴C label on either the acetyl or the D-alanine in the D-amino acid backbone would be appropriate for clin. studies. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Quality Control of 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. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine

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

Catalytic asymmetric electrochemical α-arylation of cyclic β-ketocarbonyls with anodic benzyne intermediates was written by Zhang, Qinglin;Guo, Chang. And the article was included in Youji Huaxue in 2020.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

This achieved the use of electrochem. methods to generate highly active benzyne or cyclohexyne intermediates, cleverly combined cobalt acetate with benzyne or cyclohexyne intermediates, improved the stability of the phenylyne intermediates, and successfully combined with cyclic β-ketocarbonyl compound activated by the chiral primary amine catalyst developed by the research group, and realized the synthesis of various high enantioselective α-aryl and α-cyclohexenyl derivatives In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Quality Control of 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. Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeQuality Control of 1H-Benzo[d][1,2,3]triazol-1-amine

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

Convulsant effects of abused synthetic cannabinoids JWH-018 and 5F-AB-PINACA are mediated by agonist actions at CB1 receptors in mice was written by Wilson, Catheryn D.;Tai, Sherrica;Ewing, Laura;Crane, Jasmine;Lockhart, Taylor;Fujiwara, Ryochi;Radominska-Pandya, Anna;Fantegrossi, William E.. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2019.Synthetic Route of C6H6N4 This article mentions the following:

Convulsant effects of abused synthetic cannabinoid (SCB) drugs have been reported in humans and laboratory animals, but the mechanism of these effects is not known. We compared convulsant effects of partial CB1R agonist Δ9-tetrahydrocannabinol (THC), full CB1R agonist SCBs JWH-018 and 5F-ABPINACA, and classic chem. convulsant pentylenetetrazol (PTZ) using an observational rating scale in mice. THC did not elicit convulsions, but both SCBs did so as effectively as and more potently than PTZ. SCB-elicited convulsions were attenuated by the CB1R antagonist rimonabant or by THC, or by dose regimens of THC and JWH-018, which downregulate and desensitize CB1Rs. None of these treatments altered the convulsant effects of PTZ, although diazepam attenuated PTZelicited convulsions without altering SCB-induced convulsant effects. Repeated administration of a subthreshold dose of PTZ kindled convulsant effects, but this was not observed with the SCBs, and no cross-kindling was observed Repeated administration of the SCBs resulted in tolerance to convulsant effects, but no cross-tolerance to PTZ was observed Inhibition on Phase I metabolism via nonselective inhibition of CYP450s with 1-aminobenzotriazole potentiated the hypothermic effects of the SCBs and protected against the convulsant effects of JWH-018, but not those of 5F-AB-PINACA or PTZ. Incubation of human liver microsomes with the SCBs showed that JWH-018 is eliminated via oxidation, whereas 5F-ABPINACA is not. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Synthetic Route of C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeSynthetic Route of C6H6N4

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

Mechanism and pattern of resistance to some ACCase inhibitors in winter wild oat (Avena sterilis subsp. ludoviciana (Durieu) Gillet & Magne) biotypes collected within canola fields was written by Hassanpour-bourkheili, Saeid;Gherekhloo, Javid;Kamkar, Behnam;Ramezanpour, S. Sanaz. And the article was included in Crop Protection in 2021.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

Due to the reports regarding unsuccessful control of Avena sterilis subsp. ludoviciana (Durieu) Gillet & Magne by haloxyfop-R-Me in canola fields, the following study was conducted to investigate the resistance of this weed to haloxyfop-R-Me. These biotypes were then subjected to various rates of clodinafop propargyl, sethoxydim, pinoxaden and mesosulfuron Me + iodosulfuron-Me herbicides and their and cross-resistance to clodinafop propargyl and sethoxydim was confirmed. However, no resistance was observed to pinoxaden and mesosulfuron-Me + iodosulfuron-Me herbicides. Indirect study of metabolism by P 450 using 1- aminobenzotriazole and piperonyl butoxide showed that this enzyme had no contribution to occurrence of resistance in the studied biotypes. Allele-specific PCR results indicated that Ile-2041-Asn mutation is responsible for resistance of A. sterilis subsp. ludoviciana biotypes, which was confirmed by sequencing of the samples. Since pinoxaden neg. affects canola, the growers face a serious limitation in their choice for chem. management and thus, implementation of integrated weed management such as introduction of row crops such as faba bean in crop rotation and increasing the diversity of herbicide mode of action by cultivation of crops such as sugar beet in crop rotation may prove helpful. This was the first case of A. sterilis subsp. ludoviciana resistance to ACCase inhibitors in canola fields. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Quality Control of 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 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.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine

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

Determination of metabolic profile of novel triethylamine containing thiophene S006-830 in rat, rabbit, dog and human liver microsomes was written by Hidau, Mahendra Kumar;Singh, Yeshwant;Singh, Shio Kumar. And the article was included in Drug Testing and Analysis in 2016.Formula: C6H6N4 This article mentions the following:

CDRI S006-830 is a potent triethylamine containing thiophene antitubercular compound of the Central Drug Research Institute, India. The present study aimed to conduct comprehensive metabolic investigations of CDRI S006-830 to corroborate its preclin. investigations. Preliminary metabolic investigations were performed to assess the metabolic stability, enzyme kinetics, reaction phenotyping, and metabolite identification of CDRI S006-830 in rat, rabbit, dog, and human liver microsomes using liquid chromatog. with mass spectrometry. The observed in vitro t_1/2 and Cl_int values were 9.9 ± 1.29, 4.5 ± 0.52, 4.5 ± 0.86, 17 ± 5.21 min and 69.60 ± 8.37, 152.0 ± 17.26, 152.34 ± 27.63, 33.62 ± 21.04 μL/min/mg in rat, rabbit, dog and human liver microsomes resp. These observations suggested that CDRI S006-830 rapidly metabolized in the presence of NADPH in liver microsomes of rat, rabbit and dog while moderately metabolized in human liver microsomes. It was observed that CDRI S006-830 exhibited monophasic Michaelis-Menten kinetics. The metabolism of CDRI S006-830 was primarily mediated by CYP3A4 and was deduced by CYP reaction phenotyping with known potent inhibitors. CYP3A4 involvement was also confirmed by cDNA-expressed recombinant human isoenzyme activity with different CYPs. Four major phase-I metabolites of S006-830, (M-1 to M-4) were detected in rat, rabbit, dog (except M4) and human liver microsomes. Copyright © 2015 John Wiley & Sons, Ltd. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Formula: C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) 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.Formula: C6H6N4

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

Sequential phase I metabolism of pyrethroids by duplicated CYP6P9 variants results in the loss of the terminal benzene moiety and determines resistance in the malaria mosquito Anopheles funestus was written by Nolden, Melanie;Paine, Mark J. I.;Nauen, Ralf. And the article was included in Insect Biochemistry and Molecular Biology in 2022.Category: triazoles This article mentions the following:

Pyrethroid resistance in Anopheles funestus is threatening the eradication of malaria. One of the major drivers of pyrethroid resistance in An. funestus are cytochrome P 450 monooxygenases CYP6P9a and CYP6P9b, which are found upregulated in resistant An. funestus populations from Sub-Saharan Africa and are known to metabolise pyrethroids. Here, we have functionally expressed CYP6P9a and CYP6P9b variants and investigated their interactions with azole-fungicides and pyrethroids. Some azole fungicides such as prochloraz inhibited CYP6P9a and CYP6P9b at nanomolar concentrations, whereas pyrethroids were weak inhibitors (>100μM). Amino acid sequence comparisons suggested that a valine to isoleucine substitution at position 310 in the active site cavity of CYP6P9a and CYP6P9b, resp., might affect substrate binding and metabolism We therefore swapped the residues by site directed mutagenesis to produce CYP6P9aI310V and CYP6P9bV310I. CYP6P9bV310I produced stronger metabolic activity towards coumarin substrates and pyrethroids, particularly permethrin. The V310I mutation was previously also detected in a pyrethroid resistant field population of An. funestus in Benin. Addnl., we found the first metabolite of permethrin and deltamethrin after hydroxylation, 4OH permethrin and 4OH deltamethrin, were also suitable substrates for CYP6P9-variants, and were depleted by both enzymes to a higher extent than as their resp. parent compounds (approx. 20% more active). Further, we found that both metabolites were toxic against An. funestus FANG (pyrethroid susceptible) but not towards FUMOZ-R (pyrethroid resistant) mosquitoes, the latter suggesting detoxification by overexpressed CYP6P9a and CYP6P9b. We confirmed by mass-spectrometric anal. that CYP6P9a and CYP6P9b are capable of cleaving phenoxybenzyl-ethers in type I pyrethroid permethrin and type II pyrethroid deltamethrin and that both enzymes preferentially metabolise trans-permethrin. This provides new insight into the metabolism of pyrethroids and a greater understanding of the mol. mechanisms of pyrethroid resistance in An. funestus. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Category: triazoles).

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. 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.Category: triazoles

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