Category: pyrazoles-derivatives

Synthetic Route of C4H6N2On October 15, 2021 ,《Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy》 was published in European Journal of Medicinal Chemistry. The article was written by Sagar, Satish; Singh, Sarbjit; Mallareddy, Jayapal Reddy; Sonawane, Yogesh A.; Napoleon, John V.; Rana, Sandeep; Contreras, Jacob I.; Rajesh, Christabelle; Ezell, Edward L.; Kizhake, Smitha; Garrison, Jered C.; Radhakrishnan, Prakash; Natarajan, Amarnath. The article contains the following contents:

Genetic models validated Inhibitor of nuclear factor (NF) kappa B kinase beta (IKKβ) as a therapeutic target for KRAS mutation associated pancreatic cancer. Phosphorylation of the activation loop serine residues (S177, S181) in IKKβ is a key event that drives tumor necrosis factor (TNF) α induced NF-κB mediated gene expression. Here we conducted structure activity relationship (SAR) study to improve potency and oral bioavailability of a quinoxaline analog 13-197 that was previously reported as a NFκB inhibitor for pancreatic cancer therapy. The SAR led to the identification of a novel quinoxaline urea analog 84 that reduced the levels of p-IKKβ in dose- and time-dependent studies. When compared to 13-197, analog 84 was ∼2.5-fold more potent in TNFα-induced NFκB inhibition and ∼4-fold more potent in inhibiting pancreatic cancer cell growth. Analog 84 exhibited ∼4.3-fold greater exposure (AUC0-∞) resulting in ∼5.7-fold increase in oral bioavailability (%F) when compared to 13-197. Importantly, oral administration of 84 by itself and in combination of gemcitabine reduced p-IKKβ levels and inhibited pancreatic tumor growth in a xenograft model. After reading the article, we found that the author used 1-Methylpyrazole(cas: 930-36-9Synthetic Route of C4H6N2)

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. Synthetic Route of C4H6N2

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

Safety of 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acidOn October 31, 1981 ,《1,3-Dipolar addition of pyridine N-imine to acetylenes and the use of carbon-13 NMR in several structural assignments》 appeared in Journal of Heterocyclic Chemistry. The author of the article were Anderson, Paul L.; Hasak, James P.; Kahle, Alicia D.; Paolella, Nicholas A.; Shapiro, Michael J.. The article conveys some information:

Addition of pyridine N-imine to EtO2CCCR (R = H, Me, Ph) or MeO2CCCCO2Me gave I (same R) or II, resp. Several of the 3-azapyrrocoline esters obtained were further converted into acids, amides and hydrazides. The experimental part of the paper was very detailed, including the reaction process of 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 80537-07-1Safety of 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid)

2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 80537-07-1) 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. Safety of 2-Phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid

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

HPLC of Formula: 3310-35-8On September 30, 2007 ,《Quantum-chemical study of the structure and reactivity of pyrazol-5-ones and their thio and seleno analogs: X. 1-methylpyrazol-5-one and its thio and seleno analogs in H-complex formation reactions in the gas phase and in solutions》 was published in Russian Journal of General Chemistry. The article was written by Chmutova, G. A.; Ismagilova, E. R.; Shamov, G. A.. The article contains the following contents:

The effects of specific solvation and self-association of chalcogenpyrazol-5-ones are assessed using nonempirical quantum-chem., d. functional theory (DFT), and MP2 second-order perturbation theory methods. The formation of H-complexes with water, methanol, and DMSO stabilizes all tautomeric forms, the NH tautomers of all hetero analogs being the most affected. The NH tautomers form with water 1:2 complexes which reveal cooperativity. The complexes of chalcogenpyrazolones with DMSO are more stable than the resp. complexes with water, and, therewith, the extra stabilization in continuum is less pronounced than in the case of hydration. Quant., the effects of tautomer self-association compare with the effects of interaction of chalcogenpyrazolones with proton-donor solvents. The results came from multiple reactions, including the reaction of 2-Methyl-1H-pyrazol-3(2H)-one(cas: 3310-35-8HPLC of Formula: 3310-35-8)

2-Methyl-1H-pyrazol-3(2H)-one(cas: 3310-35-8) 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. HPLC of Formula: 3310-35-8

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

In 2012,Saini, Vaneet; Sigman, Matthew S. published 《Palladium-Catalyzed 1,1-Difunctionalization of Ethylene》.Journal of the American Chemical Society published the findings.Application of 847818-74-0 The information in the text is summarized as follows:

The 1,1-difunctionalization of ethylene, with aryl/vinyl/heteroaryl transmetalating agents and vinyl electrophiles, is reported. The reaction is high-yielding under a low pressure of ethylene, and regioselectivity is generally high for the 1,1-disubstituted product. The process is highlighted by the use of heteroaromatic cross-coupling reagents, which have not been competent reaction partners in previously reported efforts. The experimental process involved the reaction of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Application of 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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application of 847818-74-0

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

In 2010,Martins, Marcos A. P.; Beck, Paulo H.; Moreira, Dayse N.; Buriol, Lilian; Frizzo, Clarissa P.; Zanatta, Nilo; Bonacorso, Helio G. published 《Straightforward microwave-assisted synthesis of 1-carboxymethyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles under solvent-free conditions》.Journal of Heterocyclic Chemistry published the findings.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole The information in the text is summarized as follows:

An efficient microwave-assisted synthesis of 1-carboxymethyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles, e.g., I, from the cyclocondensation reaction between enones and Me hydrazinocarboxylate under solvent-free conditions is reported. This process is an efficient alternative to the traditional thermal heating and furnishes the heterocyclic compounds in good to excellent yields in a short reaction time. To show the versatility of 1-carboxymethyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles, dehydration reactions of these compounds are also demonstrated. After reading the article, we found that the author used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole)

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. The application of pyrazole derivatives in the development of anticancer agents has been thoroughly investigated and verified. Moreover, the medicinal features of a number of natural products incorporating pyrazole moiety such as pyrazofurin, pyrazofurin B, pyrazole-3(5)-carboxylic acid and 4-methylpyrazole-3(5)-carboxylic acid have been reported.Recommanded Product: 3-(Trifluoromethyl)-1H-pyrazole

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

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

《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

《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

《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