Tag: 100-200

Mechanistic studies of cytochrome P450 3A4 time-dependent inhibition using two cysteine-targeting electrophiles was written by Barr, John T.;Wang, Zhican;Min, Xiaoshan;Wienkers, Henry J.;Rock, Brooke M.;Rock, Dan A.;Wienkers, Larry C.. And the article was included in Drug Metabolism & Disposition in 2020.Electric Literature of C6H6N4 This article mentions the following:

Experiments designed to identify the mechanism of cytochrome P 450 inactivation are critical to drug discovery. Small mols. irreversibly inhibit P 450 enzymic activity via two primary mechanisms: apoprotein adduct formation or heme modification. Understanding the interplay between chem. structures of reactive electrophiles and the impact on CYP3A4 structure and function can ultimately provide insights into drug design to minimize P 450 inactivation. The compound’s effect on (1) enzymic activity, (2) carbon monoxide (CO) binding capacity, (3) intact heme content, and (4) protein conformation were measured. Results showed that PM had a large time-dependent loss of enzyme activity, whereas PIA did not. The differential effect on enzymic activity between PM and PIA was mirrored in the CO binding data. Despite disruption of CO binding, neither compound affected the heme concentrations, inferring there was no destruction or alkylation of the heme. Lastly, differential scanning fluorescence showed PM-treated CYP3A4 caused a shift in the onset temperature required to induce protein aggregation, which was not observed for CYP3A4 treated with PIA. In conclusion, alkylation of CYP3A4 apoprotein can have a variable impact on catalytic activity, CO binding, and protein conformation that may be compound-dependent. These results highlight the need for careful interpretation of exptl. results aimed at characterizing the nature of P 450 enzyme inactivation. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Electric Literature 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 heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Electric Literature of C6H6N4

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

Structure and biological activity of a binuclear Co(II) complex [Co₂(Htda)₂(H₂O)₆·5 H₂O] was written by Li, Jian-jun;Li, Mei-yu;Gao, En-jun;Shen, Guang-hai. And the article was included in Shenyang Huagong Daxue Xuebao in 2014.Application In Synthesis of 1H-1,2,3-Triazole-4,5-dicarboxylic acid This article mentions the following:

The complex [Co₂(Htda)₂(H₂O)₆·5H₂O] (H₃tda = 1H-1,2,3-triazole-4,5-dicarboxylic acid) was synthesized by hydrothermal method and characterized by x-ray anal. The binding of the title complex with calf thymus DNA (CT-DNA) was studied by fluorescence spectra. Gel electrophoresis assay and the optical d. scanning experiment demonstrated the ability to cleave the pBR322 DNA of the complex. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Application In Synthesis of 1H-1,2,3-Triazole-4,5-dicarboxylic acid).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) 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. 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-1,2,3-Triazole-4,5-dicarboxylic acid

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

Small Molecule Dysregulation of TEAD Lipidation Induces a Dominant-Negative Inhibition of Hippo Pathway Signaling was written by Holden, Jeffrey K.;Crawford, James J.;Noland, Cameron L.;Schmidt, Stephen;Zbieg, Jason R.;Lacap, Jennifer A.;Zang, Richard;Miller, Gregory M.;Zhang, Yue;Beroza, Paul;Reja, Rohit;Lee, Wendy;Tom, Jeffrey Y. K.;Fong, Rina;Steffek, Micah;Clausen, Saundra;Hagenbeek, Thjis J.;Hu, Taishan;Zhou, Zheng;Shen, Hong C.;Cunningham, Christian N.. And the article was included in Cell Reports in 2020.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

The transcriptional enhanced associate domain (TEAD) family of transcription factors serves as the receptors for the downstream effectors of the Hippo pathway, YAP and TAZ, to upregulate the expression of multiple genes involved in cellular proliferation and survival. Recent work identified TEAD S-palmitoylation as critical for protein stability and activity as the lipid tail extends into a hydrophobic core of the protein. Here, we report the identification and characterization of a potent small mol. that binds the TEAD lipid pocket (LP) and disrupts TEAD S-palmitoylation. Using a variety of biochem., structural, and cellular methods, we uncover that TEAD S-palmitoylation functions as a TEAD homeostatic protein level checkpoint and that dysregulation of this lipidation affects TEAD transcriptional activity in a dominant-neg. manner. Furthermore, we demonstrate that targeting the TEAD LP is a promising therapeutic strategy for modulating the Hippo pathway, showing tumor stasis in a mouse xenograft model. 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. 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.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine

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

Tetraaquabis[4-(4H-1,2,4-triazol-4-yl)benzoato-κN¹]nickel(II) decahydrate was written by Sun, Weixuan;Yu, Yaqin;Wang, Guanjun;Wu, Xiaohui. And the article was included in Acta Crystallographica, Section E: Structure Reports Online in 2012.Synthetic Route of C9H7N3O2 This article mentions the following:

In the title compound, [Ni(C₉H₆N₃O₂)₂(H₂O)₄]·10H₂O, the Ni^II ion lies on a 2-fold rotation axis and displays a slightly distorted octahedral geometry defined by two N atoms from two monodentate 4-(1,2,4-triazol-4-yl)benzoate ligands and four H₂O mols., two of which also lie on the 2-fold rotation axis. In the crystal, the complex mols. and uncoordinated H₂O mols. are linked via intermol. O-H···N and O-H···O H bonds, forming a three-dimensional supramol. network. π-π Interactions between the benzene rings provide addnl. stability of the crystal packing [centroid-centroid distance = 3.792(2) Å]. Crystallog. data and at. coordinates are given. In the experiment, the researchers used many compounds, for example, 4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2Synthetic Route of C9H7N3O2).

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. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Synthetic Route of C9H7N3O2

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

Studies on v-triazoles. Part 4. The 4-methoxybenzyl group, a versatile N-protecting group for the synthesis of N-unsubstituted v-triazoles was written by Buckle, Derek R.;Rockell, Caroline J. M.. And the article was included in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) in 1982.Safety of Ethyl 1H-1,2,3-triazole-5-carboxylate This article mentions the following:

(EtO₂C)₂CH₂ underwent cyclocondensation with 4-MeOC₆H₄CH₂N₃ (I) to give 67% triazole II (R = OH, R¹ = CH₂C₆H₄OMe-4), which on subsequent treatment with PCl₅ in PhMe at 40° gave 65% II (R = Cl, R¹ as before) (III). III readily underwent halogen displacement to give 66-82% II (R = CN, 4-MeOC₆H₄S, PhO, R¹ = CH₂C₆H₄OMe-4). I also underwent 1,3-dipolar addition with acetylenes; thus, I with RCCCO₂Et (R = H, Ph) gave 30-45% II (R as before, R¹ = CH₂C₆H₄OMe-4). Deprotection of II (R = OH, Cl, CN, H, 4-MeOC₆H₄S, PhO, Ph, R¹ = CH₂C₆H₄OMe-4) followed by treatment with CF₃CO₂H at 65° gave 52-100% II (R as before, R¹ = H). In addition, hydrolysis of II (R = PhO, R¹ = CH₂C₆H₄OMe-4) gave 90% of the corresponding acid which was converted via its acyl chloride into the tricyclic compound IV (R = CH₂C₆H₄OMe-4), analogous deprotection of which gave 70% IV (R = H), a potential antiallergic agent. In the experiment, the researchers used many compounds, for example, Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7Safety 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. 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.Safety of Ethyl 1H-1,2,3-triazole-5-carboxylate

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

Liquid-phase ozone oxidation of condensed azoles was written by Tyupalo, N. F.;Yakobi, V. A.;Stepanyan, A. A.;Zaika, R. G.. And the article was included in Ukrainskii Khimicheskii Zhurnal (Russian Edition) in 1977.Electric Literature of C4H3N3O4 This article mentions the following:

Liquid-phase oxidation of I(X = N, CH) by O3 at 60° in H2SO4 containing MnSO4 or FeSO4 gave 83-8% II (X = CH) from benzimidazole and 65-76% II (X = N) from benzotriazole. A mechanism involving oxidation of the Fe and Mn ions by O3 was proposed. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Electric Literature of C4H3N3O4).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) 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. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Electric Literature of C4H3N3O4

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

An aggregation-induced emission fluorescence probe for evaluating the effect of CYP450 changes under tumor chemotherapy was written by Lu, Pengpeng;Huang, Yan;Zhang, Caiyun;Fu, Lili;Wang, Xiaoyan;Chen, Lingxin. And the article was included in Talanta in 2022.Recommanded Product: 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

Cancer is a complex disease with very high incidence and mortality rates every year. However, cancer drug resistance greatly mitigates the cure rates of tumors, and cytochrome P 450 (CYP450) plays an important role in the development of cisplatin resistance. We developed the aggregation-induced emission luminogen (AIEgen) TPE-CYP to monitor the changes in CYP450. The TPE-CYP fluorescent probe was successfully used to assess CYP450 levels in tumor cells and tumor tissue sections. This study presented that CYP450 level in HepG2/DDP cells (cisplatin-resistant cells) was higher than that in HepG2 cells, and the inhibition of CYP450 by 1-ABT effectively improved the tumor resistance. Thus, CYP450 plays a key role in the development of tumor resistance. The synergistic effect of 1-ABT and the chemotherapeutic agent cisplatin was superior to that of cisplatin alone in tumor-bearing mice. The TPE-CYP probe will provide an idea for the clin. implementation of individualized tumor treatment strategies, through the accurate monitoring of CYP450. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Recommanded Product: 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. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Recommanded Product: 1H-Benzo[d][1,2,3]triazol-1-amine

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

TXA709, an FtsZ-targeting benzamide prodrug with improved pharmacokinetics and enhanced in vivo efficacy against methicillin-resistant Staphylococcus aureus was written by Kaul, Malvika;Mark, Lilly;Zhang, Yongzheng;Parhi, Ajit K.;Lyu, Yi Lisa;Pawlak, Joan;Saravolatz, Stephanie;Saravolatz, Louis D.;Weinstein, Melvin P.;La Voie, Edmond J.;Pilch, Daniel S.. And the article was included in Antimicrobial Agents and Chemotherapy in 2015.Computed Properties of C6H6N4 This article mentions the following:

The clin. development of FtsZ-targeting benzamide compounds like PC190723 has been limited by poor drug-like and pharmacokinetic properties. Development of prodrugs of PC190723 (e.g., TXY541) resulted in enhanced pharmaceutical properties, which, in turn, led to improved i.v. efficacy as well as the first demonstration of oral efficacy in vivo against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Despite being efficacious in vivo, TXY541 still suffered from suboptimal pharmacokinetics and the requirement of high efficacious doses. We describe here the design of a new prodrug (TXA709) in which the Cl group on the pyridyl ring has been replaced with a CF3 functionality that is resistant to metabolic attack. As a result of this enhanced metabolic stability, the product of the TXA709 prodrug (TXA707) is associated with improved pharmacokinetic properties (a 6.5-fold-longer half-life and a 3-fold-greater oral bioavailability) and superior in vivo antistaphylococcal efficacy relative to PC190723. We validate FtsZ as the antibacterial target of TXA707 and demonstrate that the compound retains potent bactericidal activity against S. aureus strains resistant to the current standard-of-care drugs vancomycin, daptomycin, and linezolid. These collective properties, coupled with minimal observed toxicity to mammalian cells, establish the prodrug TXA709 as an antistaphylococcal agent worthy of clin. development. 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. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities.Computed Properties of C6H6N4

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

Reaction of 3-nitro- and 3-bromo-3-nitroacrylates with sodium azide was written by Anisimova, N. A.;Berestovitskaya, V. M.;Berkova, G. A.;Makarova, N. G.. And the article was included in Russian Journal of Organic Chemistry in 2007.Safety of Ethyl 1H-1,2,3-triazole-5-carboxylate This article mentions the following:

Reactions of 3-nitro- and 3-bromo-3-nitroacrylates with NaN₃ proceed as 1,3-dipolar cycloaddition and lead to the formation of triazole- and nitrotriazolecarboxylates, and also of azido- and azidonitropropenoates. In the experiment, the researchers used many compounds, for example, Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7Safety 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. 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.Safety of Ethyl 1H-1,2,3-triazole-5-carboxylate

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

Effective route for synthesis of novel aromatic pyridine derivates with polyamino polycarboxyl units was written by Gu, GuoLiang;Zhou, TaiYan. And the article was included in Journal of the Chemical Society of Pakistan in 2017.Computed Properties of C5H7N3O2 This article mentions the following:

A series of novel aromatic mols. with polyamino polycarboxyl were designed, synthesized and characterized in detail based on elemental anal., IR, mass, proton NMR spectroscopy. The synthetic route was optimized. The yield of second synthesis step over 91 % as a result of the catalyst (LiBr) used. Due to the fascinating structure with multiple N and O donor atoms, it may be potential applications in organic light emitting diodes (OLED). In the experiment, the researchers used many compounds, for example, Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7Computed Properties of C5H7N3O2).

Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7) 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. 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.Computed Properties of C5H7N3O2

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