Category: pyrazoles-derivatives

In 1977,Gilman, Norman W.; Holland, Betty C.; Walsh, Gregory R.; Fryer, R. Ian published 《Nucleophilic displacement of aromatic fluorine. Part V. Use of nitrogen heterocycles as nucleophiles》.Journal of Heterocyclic Chemistry published the findings.Recommanded Product: 15366-34-4 The information in the text is summarized as follows:

I (R = F) reacted with imidazole, 2-methylimidazole, 3,5-bis(acetoxymethyl)pyrazole, pyrrole, di-Et 2-methyl-4,5-imidazoledicarboxylate, Me pyrrole-2-carboxylate, di-Me pyrazole-3,5-dicarboxylate, and Me pyrazole-3-carboxylate to give N-aryl heterocycles, e.g., II. In some cases the analogous reaction with I (R = Cl) failed to occur. Some substitution reactions of other aromatic fluorides were also examined The results came from multiple reactions, including the reaction of Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Recommanded Product: 15366-34-4)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) 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: 15366-34-4

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

Li, Weipeng; Yuan, Dandan; Wang, Guoqiang; Zhao, Yue; Xie, Jin; Li, Shuhua; Zhu, Chengjian published an article on February 20 ,2019. The article was titled 《Cooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight》, and you may find the article in Journal of the American Chemical Society.Quality Control of 1-Methylpyrazole The information in the text is summarized as follows:

In the presence of (Me2S)AuCl and AgOAc, pyrazoles such as 1-phenylpyrazole underwent chemoselective and regioselective oxidative dehydrogenative coupling reactions with fluorinated arenes and pyridines such as 2,3,5,6-tetrafluoropyridine mediated by PhI(OAc)2 in 1,4-dioxane to yield (fluoroaryl)pyrazoles such as I. The mechanism of the oxidative coupling reaction was studied by determination of the reaction kinetics, kinetic isotope effects, and deuterium exchange, by generation and preparation of gold and silver complexes as potential intermediates, and by DFT calculations of transition state structures and energies for arene metalation, transmetalation, and reductive elimination reactions. Silver acetate is determined to be is the actual catalyst for C-H activation of electron-poor arenes, rather than gold(I) complexes. A mechanism of gold/silver dual catalysis is proposed, in which silver is responsible for the activation of electron-poor fluoroarenes via a concerted metalation-deprotonation pathway, and gold is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that C-H activation of pyrazoles by fluoroarylgold complexes is most likely the rate-limiting step. The experimental part of the paper was very detailed, including the reaction process of 1-Methylpyrazole(cas: 930-36-9Quality Control of 1-Methylpyrazole)

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. Quality Control of 1-Methylpyrazole

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

Kwiatkowski, Jacek; Liu, Boping; Pang, Shermaine; Binte Ahmad, Nur Huda; Wang, Gang; Poulsen, Anders; Yang, Haiyan; Poh, Yong Rui; Tee, Doris Hui Ying; Ong, Esther; Retna, Priya; Dinie, Nurul; Kwek, Perlyn; Wee, John Liang Kuan; Manoharan, Vithya; Low, Choon Bing; Seah, Peck Gee; Pendharkar, Vishal; Sangthongpitag, Kanda; Joy, Joma; Baburajendran, Nithya; Jansson, Anna Elisabet; Nacro, Kassoum; Hill, Jeffrey; Keller, Thomas H.; Hung, Alvin W. published an article on January 23 ,2020. The article was titled 《Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2》, and you may find the article in Journal of Medicinal Chemistry.Quality Control of 4-Bromo-5-cyclopropyl-1H-pyrazole The information in the text is summarized as follows:

Dysregulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers. Mitogen-activated protein kinase (MAPK) interacting kinases 1 and 2 (MNK1 and MNK2) play a fundamental role in activation of eIF4E. Structure-activity relationship-driven expansion of a fragment hit led to discovery of dual MNK1 and MNK2 inhibitors based on a novel pyridine-benzamide scaffold. The compounds possess promising in vitro and in vivo pharmacokinetic profiles and show potent on target inhibition of eIF4E phosphorylation in cells. In the experiment, the researchers used 4-Bromo-5-cyclopropyl-1H-pyrazole(cas: 957345-28-7Quality Control of 4-Bromo-5-cyclopropyl-1H-pyrazole)

4-Bromo-5-cyclopropyl-1H-pyrazole(cas: 957345-28-7) 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. Quality Control of 4-Bromo-5-cyclopropyl-1H-pyrazole

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

Name: Methyl 1H-pyrazole-3-carboxylateIn 2021 ,《Route Design to Manufacture: Synthesis of the Heterocyclic Fragment of AZD5718 Using a Non-cryogenic Lithiation-Alkoxycarbonylation Reaction》 was published in Organic Process Research & Development. The article was written by Burns, Matthew; Perkins, Dave; Chan, Lai C.; Pilling, Michael J.; Jawor-Baczynska, Anna; Mullen, Alexander K.; Steven, Alan; Wimsey, Chris; Elmekawy, Ahmed; Lamacraft, Alex; Dobson, Benjamin C.; McMillan, Angus E.; Hose, David R. J.; Inglesby, Phillip A.; Raw, Steven A.; Jones, Martin F.. The article contains the following contents:

Route design and process development of the small nitrogen heterocycle I, a constituent of AZD5718 (II), is described. The novel synthetic sequence to I involves a desymmetrizing alkylation of 4-nitropyrazole, a non-cryogenic lithiation-alkoxycarbonylation, and a global reduction-cyclization. This new synthetic route was implemented in the manufacture of I and was able to deliver over 1000 kg of product with a yield of 77% over the three stages. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Name: Methyl 1H-pyrazole-3-carboxylate)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) 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.Name: Methyl 1H-pyrazole-3-carboxylate

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

Quality Control of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleIn 2016 ,《Design, synthesis and biological evaluation of novel cholesteryl ester transfer protein inhibitors bearing a cycloalkene scaffold》 appeared in European Journal of Medicinal Chemistry. The author of the article were Liu, Chunchi; Luo, Changqun; Hao, Lijuan; Wu, Qiong; Xie, Honglei; Zhao, Shizhen; Hao, Chenzhou; Zhao, Dongmei; Cheng, Maosheng. The article conveys some information:

Cholesteryl ester transfer protein (CETP) is a potential target for cardiovascular disease therapy as inhibition of CETP leads to increased HDL-C in humans. Based on the structure of Merck’s biphenyl CETP inhibitor, authors designed novel N,N-substituted-cycloalkenyl-methylamine scaffold derivatives by utilizing core replacement and conformational restriction strategies. Consequently, twenty-eight compounds were synthesized and evaluated for their inhibitory activity against CETP. Their preliminary structure-activity relationships (SARs) studies indicate that polar substituents were tolerated in moiety A and hydrophobic alkyl groups at the 5-position of cyclohexene were critical for potency. Among them, compound 17a, bearing an N-(5-pyrazolyl-pyrimidin-2-yl)-cycloalkenyl- methylamine scaffold, exhibited excellent CETP inhibitory activity (IC50 = 0.07 μM) in vitro. Furthermore, it showed an acceptable pharmacokinetic profile in S-D rats and efficient HDL-C increase in high-fat fed hamsters. In the part of experimental materials, we found many familiar compounds, such as 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Quality Control 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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Quality Control 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

Computed Properties of C5H6N2O2In 1976 ,《Unusual reaction of 3-carbomethoxy-Δ2-pyrazoline in the presence of lead tetraacetate》 appeared in Khimiya Geterotsiklicheskikh Soedinenii. The author of the article were Akhrem, A. A.; Kvasyuk, E. I.; Mikhailopulo, I. A.. The article conveys some information:

Treatment of pyrazolinecarboxylate I with Pb(OAc)4 in dry C6H6 30 min at 70° gave 71% II and 14% III whose structures were confirmed by ir, uv, and NMR spectra. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Computed Properties of C5H6N2O2)

Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4) 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.Computed Properties of C5H6N2O2

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

Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleIn 2022 ,《Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers》 appeared in Journal of Medicinal Chemistry. The author of the article were Smith, Christopher R.; Aranda, Ruth; Bobinski, Thomas P.; Briere, David M.; Burns, Aaron C.; Christensen, James G.; Clarine, Jeffery; Engstrom, Lars D.; Gunn, Robin J.; Ivetac, Anthony; Jean-Baptiste, Ronald; Ketcham, John M.; Kobayashi, Masakazu; Kuehler, Jon; Kulyk, Svitlana; Lawson, J. David; Moya, Krystal; Olson, Peter; Rahbaek, Lisa; Thomas, Nicole C.; Wang, Xiaolun; Waters, Laura M.; Marx, Matthew A.. The article conveys some information:

The PRMT5•MTA complex has recently emerged as a new synthetically lethal drug target for the treatment of MTAP-deleted cancers. Here, we report the discovery of development candidate MRTX1719. MRTX1719 is a potent and selective binder to the PRMT5•MTA complex and selectively inhibits PRMT5 activity in MTAP-deleted cells compared to MTAP-wild-type cells. Daily oral administration of MRTX1719 to tumor xenograft-bearing mice demonstrated dose-dependent inhibition of PRMT5-dependent sym. dimethylarginine protein modification in MTAP-deleted tumors that correlated with antitumor activity. A 4-(aminomethyl)phthalazin-1(2H)-one hit was identified through a fragment-based screen, followed by x-ray crystallog., to confirm binding to the PRMT5•MTA complex. Fragment growth supported by structural insights from x-ray crystallog. coupled with optimization of pharmacokinetic properties aided the discovery of development candidate MRTX1719. 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: 847818-74-0Reference 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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Reference 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

In 2022,Bin, Huachao; Chen, Pei; Wu, Ming; Wang, Falu; Lin, Guifeng; Pan, Shulei; Liu, Jingming; Mu, Bo; Nan, Jinshan; Huang, Qiao; Li, Linli; Yang, Shengyong published an article in European Journal of Medicinal Chemistry. The title of the article was 《Discovery of a potent and highly selective inhibitor of ataxia telangiectasia mutated and Rad3-Related (ATR) kinase: Structural activity relationship and antitumor activity both in vitro and in vivo》.COA of Formula: C10H17BN2O2 The author mentioned the following in the article:

Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is an important regulator of the DNA damage response (DDR), especially in response to replication stress (RS). Tumor cells with ataxia-telangiectasia mutated (ATM) kinase loss of function or DDR defects that promote replicative stress are often more reliant on ATR for survival, highlighting ATR as a good antitumor target under the principle of synthetic lethality. Herein we report the discovery of a potent and highly selective ATR inhibitor, SKLB-197, which was obtained through structural optimization and structure-activity relationship (SAR) studies towards a hit compound (Cpd-1). SKLB-197 showed an IC50 value of 0.013 μM against ATR but very weak or no activity against other 402 protein kinases. It displayed potent antitumor activity against ATM-deficent tumors both in vitro and in vivo. In addition, this compound exhibited good pharmacokinetic properties. Overall, SKLB-197 could be a promising lead compound for drug discovery targeting ATR and deserves further in-depth studies. 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: 847818-74-0COA of Formula: 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. COA of Formula: C10H17BN2O2

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

Xie, Jizhao; Xu, Huanji; Wu, Xinduo; Xie, Yunfeng; Lu, Xiuhong; Wang, Lisheng published their research in Bioorganic & Medicinal Chemistry Letters in 2021. The article was titled 《Design, synthesis and anti-TNBC activity of Azeliragon triazole analogues》.Application of 847818-74-0 The article contains the following contents:

Triple-neg. breast cancer (TNBC) is the most aggressive subtype of breast cancer. Many studies have shown a significant increase in the marker signal of the receptor for advanced glycation end-products (RAGE) with the malignant progression of tumor growth, metastasis and recurrence of breast cancer, including TNBC of primary tumors and lymph node metastases. Azeliragon is a RAGE inhibitor and it has been shown to actively inhibit the TNBC cell line, SUM149 (IC50 = 5.292 ± 0.310 μM). In order to develop a new anti-TNBC agent, we designed, synthesized and screened 26 Azeliragon triazole analogs to determine their anti-TNBC activities in vitro. The most active compound was KC-10 (3-(4-(5-butyl-1-(4′-chloro-[1,1′-biphenyl]-4-yl)-1H-1,2,4-triazol-3-yl)phenoxy)-N, N-diethylpropan-1-amine) with an IC50 value of 0.220 ± 0.034 μM. 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: 847818-74-0Application 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, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Application of 847818-74-0

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

The author of 《Inhibition of fatty acid release by pyrazole derivatives》 were Bizzi, Adalgisa. And the article was published in Progress in Biochemical Pharmacology in 1968. Recommanded Product: (3-methyl-1H-pyrazol-5-yl)methanol The author mentioned the following in the article:

In rats, 3,5-dimethylpyrazole (I) is quiet active in decreasing free fatty acid (FFA) and glycerol in adipose tissue as well as in plasma with doses as low as 50 μg/kg, i.p. In plasma after 2 hr, I and 5-carboxyl-3-methylpyrazole (II) appear more active than 3-methylpyrazole. When tested in vitro on the release of FFA from adipose tissue, II appeared to be the most active. The 3 compounds when given orally in doses of 0.75-30 mg/kg also produce up to a 50% decrease in plasma triglycerides. This effect is proportional to the dose used. The experimental part of the paper was very detailed, including the reaction process of (3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7Recommanded Product: (3-methyl-1H-pyrazol-5-yl)methanol)

(3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7) 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: (3-methyl-1H-pyrazol-5-yl)methanol

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