pyrazoles-derivatives

In 2016,Tremmel, Tim; Puzik, Andreas; Gehring, Andre P.; Bracher, Franz published 《Canthin-4-ones as Novel Antibacterial Agents》.Archiv der Pharmazie (Weinheim, Germany) published the findings.Safety of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole The information in the text is summarized as follows:

Based on the chemotype of canthin-4-one alkaloids with moderate antimicrobial activity, a collection of variously substituted canthin-4-ones and desaza analogs were synthesized. Key steps in the syntheses were regioselective halogenations of (desaza) canthin-4-one, followed by Pd-catalyzed cross-coupling reactions. The in vitro screening for antimicrobial activity revealed that two 5-substituted canthin-4-ones (3-pyridyl, 2-bromophenyl) exhibit significant activity against Streptococcus entericus, coupled with high selectivity and the lack of cytotoxicity against mammalian cells. The intact canthin-4-one ring system was demonstrated to be essential for antibacterial activity. In the experiment, the researchers used many compounds, for example, 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Safety of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Safety of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor》 was written by Xu, Guozhang; Gaul, Michael D.; Liu, Zhijie; DesJarlais, Renee L.; Qi, Jenson; Wang, Weixue; Krosky, Daniel; Petrounia, Ioanna; Milligan, Cynthia M.; Hermans, An; Lu, Hua-Rong; Huang, Devine Zheng; Xu, June Zhi; Spurlino, John C.. Recommanded Product: 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole And the article was included in Bioorganic & Medicinal Chemistry Letters in 2020. The article conveys some information:

G-protein coupled receptor kinase 2 (GRK2), which is upregulated in the failing heart, appears to play a critical role in heart failure (HF) progression in part because enhanced GRK2 activity promotes dysfunction of β-adrenergic signaling and myocyte death. An orally bioavailable GRK2 inhibitor could offer unique therapeutic outcomes that cannot be attained by current heart failure treatments that directly target GPCRs or angiotensin-converting enzyme. Herein, we describe the discovery of a potent, selective, and orally bioavailable GRK2 inhibitor, 8h, through high-throughput screening, hit-to-lead optimization, structure-based design, mol. modeling, synthesis, and biol. evaluation. In the cellular target engagement assays, 8h enhances isoproterenol-mediated cyclic adenosine 3′,5′-monophosphate (cAMP) production in HEK293 cells overexpressing GRK2. Compound 8h was further evaluated in a human stem cell-derived cardiomyocyte (HSC-CM) contractility assay and potentiated isoproterenol-induced beating rate in HSC-CMs. In the experiment, the researchers used 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Recommanded Product: 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)

3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. Recommanded Product: 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Organophotochemical SNAr Reactions of Mildly Electron-Poor Fluoroarenes》 was written by Sheridan, Thomas; Yayla, Hatice G.; Lian, Yajing; Genovino, Julien; Monck, Nat; Burton, Jonathan W.. Safety of 3-(Trifluoromethyl)-1H-pyrazole And the article was included in European Journal of Organic Chemistry in 2020. The article conveys some information:

C-F functionalization of arenes with a range of alc. and pyrazole nucleophiles has been achieved without the need for metal catalysts or highly electron-poor substrates. Treatment of fluoroarenes with alcs. or pyrazoles and DDQ under irradiation by blue LED light provides the corresponding substituted products. The procedure is complementary to classical SNAr chem. which generally requires basic reaction conditions and high temperatures, and provides products under non-basic conditions at ≈ 40°C. The results came from multiple reactions, including the reaction of 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Safety of 3-(Trifluoromethyl)-1H-pyrazole)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Safety of 3-(Trifluoromethyl)-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Wang, Tianqi; Zhang, Rong; Liu, Yang; Fang, Zhen; Zhang, Hailin; Fan, Yan; Yang, Shengyong; Xiang, Rong published an article in 2021. The article was titled 《Discovery of a new class of JMJD6 inhibitors and structure-activity relationship study》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.Computed Properties of C10H17BN2O2 The information in the text is summarized as follows:

JmjC domain-containing protein 6 (JMJD6) has been thought as a potential target for various diseases particularly cancer. However, few selective JMJD6 inhibitors have been reported. In this investigation, mol. docking and biol. activity evaluation were performed to retrieve new JMJD6 inhibitors, which led to the identification of a hit compound, J2. Further structural optimization and structure-activity relationship (SAR) anal. towards J2 were carried out, which gave a new potent JMJD6 inhibitor, 7p. This compound showed an IC50 value of 0.681μM against JMJD6, but displayed no activity against other tested JmjC domain-containing protein family members, indicating good selectivity (>100 fold). Collectively, this investigation offers a selective JMJD6 inhibitor, which could be taken as a lead compound for subsequent drug discovery targeting JMJD6. The experimental part of the paper was very detailed, including the reaction process of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Computed Properties of C10H17BN2O2)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Computed Properties of C10H17BN2O2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Akiu, Mayuko; Tsuji, Takashi; Sogawa, Yoshitaka; Terayama, Koji; Yokoyama, Mika; Tanaka, Jun; Asano, Daigo; Sakurai, Ken; Sergienko, Eduard; Sessions, E. Hampton; Gardell, Stephen J.; Pinkerton, Anthony B.; Nakamura, Tsuyoshi published an article in 2021. The article was titled 《Discovery of 1-[2-(1-methyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-3-(pyridin-4-ylmethyl)urea as a potent NAMPT (nicotinamide phosphoribosyltransferase) activator with attenuated CYP inhibition》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.HPLC of Formula: 847818-74-0 The information in the text is summarized as follows:

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step of the NAD+ salvage pathway. Since NAD+ plays a pivotal role in many biol. processes including metabolism and aging, activation of NAMPT is an attractive therapeutic target for treatment of diverse array of diseases. Herein, we report the continued optimization of novel urea-containing derivatives which were identified as potent NAMPT activators. Early optimization of HTS hits afforded compound 12 (I) , with a triazolopyridine core, as a lead compound CYP direct inhibition (DI) was identified as an issue of concern, and was resolved through modulation of lipophilicity to culminate in 1-[2-(1-methyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-3-(pyridin-4-ylmethyl)urea (21, II), which showed potent NAMPT activity accompanied with attenuated CYP DI towards multiple CYP isoforms. The results came from multiple reactions, including the reaction of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0HPLC of Formula: 847818-74-0)

1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. HPLC of Formula: 847818-74-0

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Cytochrome P450 1A2 is the most important enzyme for hepatic metabolism of the metamizole metabolite 4-methylaminoantipyrine》 was written by Bachmann, Fabio; Meyer zu Schwabedissen, Henriette E.; Duthaler, Urs; Krahenbuehl, Stephan. Electric Literature of C4H6N2 And the article was included in British Journal of Clinical Pharmacology on April 30 ,2022. The article conveys some information:

Metamizole (dipyrone) is a prodrug not detectable in serum or urine after oral ingestion. The primary metabolite, 4-methylaminoantipyrine (4-MAA), can be N-demethylated to 4-aminoantipyrine (4-AA) or oxidized to 4-formylaminoantipyrine (4-FAA) by cytochrome P 450 (CYP)-dependent reactions. We aimed to identify the CYPs involved in 4-MAA metabolism and to quantify the effect of CYP inhibition on 4-MAA metabolism We investigated the metabolism of 4-MAA in vitro using CYP expressing supersomes and the pharmacokinetics of metamizole in the presence of CYP inhibitors in male subjects. The experiments in supersomes revealed CYP1A2 as the major CYP for 4-MAA N-demethylation and 4-FAA formation with CYP2C19 and CYP2D6 contributing to N-demethylation. In the clin. study, we investigated the influence of ciprofloxacin (CYP1A2 inhibitor), fluconazole (CYP2C19 inhibitor) and the combination ciprofloxacin/fluconazole on the pharmacokinetics of metamizole in n = 12 male subjects in a randomized, placebo-controlled, double-blind study. The geometric mean ratios for the area under the concentration-time curve of 4-MAA after/before treatment were 1.17 (90% CI 1.09-1.25) for fluconazole, 1.51 (90% CI 1.42-1.60) for ciprofloxacin and 1.92 (90% CI 1.81-2.03) for ciprofloxacin/fluconazole. Fluconazole increased the half-life of 4-MAA from 3.22 h by 0.47 h (95% CI 0.13-0.81, P < .05), ciprofloxacin by 0.69 h (95% CI 0.44-0.94, P < .001) and fluconazole/ciprofloxacin by 2.85 h (95% CI 2.48-3.22, P < .001). CYP1A2 is the major CYP for the conversion of 4-MAA to 4-AA and 4-FAA. The increase in 4-MAA exposure by the inhibition of CYP1A2 and by the combination CYP1A2/CYP2C19 may be relevant for dose-dependent adverse reactions of 4-MAA. In addition to this study using 1-Methylpyrazole, there are many other studies that have used 1-Methylpyrazole(cas: 930-36-9Electric Literature of C4H6N2) was used in this study.

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.Electric Literature of C4H6N2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Design and Synthesis of Minimalist Terminal Alkyne-Containing Diazirine Photo-Crosslinkers and Their Incorporation into Kinase Inhibitors for Cell- and Tissue-Based Proteome Profiling》 was published in Angewandte Chemie, International Edition in 2013. These research results belong to Li, Zhengqiu; Hao, Piliang; Li, Lin; Tan, Chelsea Y. J.; Cheng, Xiamin; Chen, Grace Y. J.; Sze, Siu Kwan; Shen, Han-Ming; Yao, Shao Q.. COA of Formula: C12H8BrN3O The article mentions the following:

A minimalist clickable photo-crosslinker was incorporated with numerous small-mol. kinase inhibitors. The resulting probes were used for both in vitro (cell lysates) and in situ (live cells) proteome profiling, for large-scale identification of their potential cellular kinase targets and shows improved outcomes over previous probes. In the experimental materials used by the author, we found 4-(3-Bromopyrazolo[1,5-a]pyrimidin-6-yl)phenol(cas: 945376-95-4COA of Formula: C12H8BrN3O)

4-(3-Bromopyrazolo[1,5-a]pyrimidin-6-yl)phenol(cas: 945376-95-4) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. COA of Formula: C12H8BrN3O

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

《Ligand-controlled Regiodivergent C-H Alkenylation of Pyrazoles and its Application to the Synthesis of Indazoles》 was published in Angewandte Chemie, International Edition in 2017. These research results belong to Kim, Hyun Tae; Ha, Hyeri; Kang, Geunhee; Kim, Og Soon; Ryu, Ho; Biswas, Abul Kalam; Lim, Sang Min; Baik, Mu-Hyun; Joo, Jung Min. HPLC of Formula: 52096-24-9 The article mentions the following:

Regioselective C4-, C5-, and di-alkenylations of pyrazoles were achieved. An electrophilic Pd catalyst generated by trifluoroacetic acid (TFA) and 4,5-diazafluoren-9-one (DAF) leads to C4-alkenylation, whereas KOAc and mono-protected amino acid (MPAA) ligand Ac-Val-OH give C5-alkenylation. A combination of palladium acetate, silver carbonate, and pivalic acid affords dialkenylation products. Annulation through sequential alkenylation, thermal 6π-electrocyclization, and oxidation gives functionalized indazoles. This comprehensive strategy greatly expands the range of readily accessible pyrazole and indazole derivatives, enabling useful regiodivergent C-H functionalization of pyrazoles and other heteroaromatic systems. After reading the article, we found that the author used 1-Butyl-1H-pyrazole(cas: 52096-24-9HPLC of Formula: 52096-24-9)

1-Butyl-1H-pyrazole(cas: 52096-24-9) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.HPLC of Formula: 52096-24-9

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In 2022,Bioinorganic Chemistry and Applications included an article by Kasparkova, Jana; Kostrhunova, Hana; Novohradsky, Vojtech; Logvinov, Alexey A.; Temnov, Viktor V.; Borisova, Nataliya E.; Podrugina, Tatiana A.; Markova, Lenka; Starha, Pavel; Nazarov, Alexey. A.; Brabec, Viktor. Recommanded Product: 930-36-9. The article was titled 《Novel cis-Pt(II) complexes with alkylpyrazole ligands: synthesis, characterization, and unusual mode of anticancer action》. The information in the text is summarized as follows:

One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biol. (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochem. characterization, biol. effects, and mechanisms of action of four new analogs of conventional cisplatin, namely, cis-Pt(II) complexes containing either Me or Et pyrazole N-donor ligands and chlorido or iodido ligands. It is noteworthy that while chlorido complexes display activity in a variety of cancer cell lines comparable to cisplatin, iodido complexes are considerably more potent due to their enhanced hydrophobicity and consequently enhanced cellular accumulation. Moreover, all of the studied Pt(II) alkylpyrazole complexes display a higher selectivity for tumor cells and effectively overcome the acquired resistance to cisplatin. Further results focused on the mechanism of action of the studied complexes and showed that in contrast to cisplatin and several platinum-based antitumor drugs, DNA damage by the investigated Pt(II)-alkylpyrazole complexes does not play a major role in their mechanism of action. Our findings demonstrate that inhibition of the tubulin kinesin Eg5, which is essential for forming a functional mitotic spindle, plays an important role in their mechanism of antiproliferative action. In the experimental materials used by the author, we found 1-Methylpyrazole(cas: 930-36-9Recommanded Product: 930-36-9)

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Recommanded Product: 930-36-9

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Kamal, Ahmed; Tamboli, Jaki R.; Vishnuvardhan, M. V. P. S.; Adil, S. F.; Nayak, V. Lakshma; Ramakrishna, S. published an article in Bioorganic & Medicinal Chemistry Letters. The title of the article was 《Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents》.Computed Properties of C12H12N2O2 The author mentioned the following in the article:

A series of different heteroaromatic linked 4β-amidopodophyllotoxin conjugates were synthesized and evaluated for anticancer activity against five human cancer cell lines. Among the series, one of the compound I showed significant antiproliferative activity in A549 (lung cancer) cell line. Flow cytometric anal. showed that I arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that I induces cell death by apoptosis. The experimental part of the paper was very detailed, including the reaction process of Methyl 3-(p-tolyl)-1H-pyrazole-5-carboxylate(cas: 192701-73-8Computed Properties of C12H12N2O2)

Methyl 3-(p-tolyl)-1H-pyrazole-5-carboxylate(cas: 192701-73-8) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Computed Properties of C12H12N2O2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics