Tag: 100-200

Recommanded Product: 474432-62-7On March 24, 2016, Getlik, Matthaus; Smil, David; Zepeda-Velazquez, Carlos; Bolshan, Yuri; Poda, Gennady; Wu, Hong; Dong, Aiping; Kuznetsova, Ekaterina; Marcellus, Richard; Senisterra, Guillermo; Dombrovski, Ludmila; Hajian, Taraneh; Kiyota, Taira; Schapira, Matthieu; Arrowsmith, Cheryl H.; Brown, Peter J.; Vedadi, Masoud; Al-awar, Rima published an article in Journal of Medicinal Chemistry. The article was 《Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)》. The article mentions the following:

WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small mol. ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity. Initial structure-activity relationship studies identified N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) benzamides as potent and selective antagonists of this protein-protein interaction. Guided by crystal structure data and supported by in silico library design, we optimized the scaffold by varying the C-1 benzamide and C-5 substituents. This allowed us to develop the first highly potent (Kdisp < 100 nM) small mol. antagonists of the WDR5-MLL1 interaction and demonstrate that N-(4-(4-methylpiperazin-1-yl)-3'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide 16d (OICR-9429) is a potent and selective chem. probe suitable to help dissect the biol. role of WDR5. In the experiment, the researchers used Pyrazolo[1,5-a]pyridine-7-carboxylic acid(cas: 474432-62-7Recommanded Product: 474432-62-7)

Pyrazolo[1,5-a]pyridine-7-carboxylic acid(cas: 474432-62-7) 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: 474432-62-7

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

Synthetic Route of C4H3F3N2In 2021 ,《Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)》 was published in Journal of Medicinal Chemistry. The article was written by Kotian, Pravin L.; Wu, Minwan; Vadlakonda, Satish; Chintareddy, Venkat; Lu, Pengcheng; Juarez, Luis; Kellogg-Yelder, Debra; Chen, Xilin; Muppa, Saritha; Chambers-Wilson, Ramanda; Davis Parker, Cynthia; Williams, Jason; Polach, Kevin J.; Zhang, Weihe; Raman, Krishnan; Babu, Yarlagadda S.. The article contains the following contents:

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50 000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-mol. drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clin. trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration’s approval for the prophylactic treatment of HAE attacks in patients 12 years and older. In the experiment, the researchers used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Synthetic Route of C4H3F3N2)

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.Synthetic Route of C4H3F3N2

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

Application of 844501-71-9In 2011 ,《SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Bonnet, Muriel; Flanagan, Jack U.; Chan, Denise A.; Lai, Edwin W.; Nguyen, Phuong; Giaccia, Amato J.; Hay, Michael P.. The article conveys some information:

We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative mol. field anal. (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chem. features of the chemotype. We now report the further mol. alignment-guided exploration of the chemotype to discover potent and selective PAT analogs. The contribution of the central thiazole ring was explored using a series of five- and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a pos. steric CoMFA contour adjacent to the pyridyl ring using Pd-catalyzed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, resp. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-pos. cell line RCC4-VHL. Active analogs selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realizing the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumor suppressor gene is reported. The experimental part of the paper was very detailed, including the reaction process of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Application of 844501-71-9)

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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application of 844501-71-9

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

《Synthesis of 2,2,2-trifluoroethyl 1H-pyrazole carboxylates: Insight into the mechanism of trichloromethyl group hydrolysis》 was written by Goncalves, Helena A.; Pereira, Bruna A.; Teixeira, Wystan K. O.; Moura, Sidnei; Flores, Darlene C.; Flores, Alex F. C.. HPLC of Formula: 15366-34-4This research focused ontrichloro methoxyalkenone trifluoroethanol cyclocondensation hydrolysis; methyl pyrazole carboxylate trifluoroethyl pyrazole carboxylate preparation green chem; trifluoroethanol trichloro hydroxyalkenone cyclocondensation; trifluoroethyl pyrazole carboxylate preparation green chem. The article conveys some information:

One-pot synthesis of 2,2,2-trifluoroethyl 1H-pyrazole-5(3)-carboxylates and via cyclocondensation of 1,1,1-trichloro-4-alkoxy-3-alken-2-ones, 1,1,1-trichloro-2,4-alkanediones and 1-aryl-4,4,4-trichloro-1,3-butanediones with hydrazine hydrochloride in 2,2,2-trifluoroethanol (TFE) was reported. Considering the low nucleophilicity of TFE in relation to methanol or ethanol, the results provided evidence for the mechanism of hydrolysis of the trichloromethyl group attached to the 1H-pyrazol ring. In the experiment, the researchers used Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4HPLC of Formula: 15366-34-4)

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.HPLC of Formula: 15366-34-4

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

《Design, Synthesis, and Biological Activity of 1,2,3-Triazolobenzodiazepine BET Bromodomain Inhibitors》 was written by Sharp, Phillip P.; Garnier, Jean-Marc; Hatfaludi, Tamas; Xu, Zhen; Segal, David; Jarman, Kate E.; Jousset, Helene; Garnham, Alexandra; Feutrill, John T.; Cuzzupe, Anthony; Hall, Peter; Taylor, Scott; Walkley, Carl R.; Tyler, Dean; Dawson, Mark A.; Czabotar, Peter; Wilks, Andrew F.; Glaser, Stefan; Huang, David C. S.; Burns, Christopher J.. Recommanded Product: 844501-71-9This research focused ontriazolo benzo diazepine preparation BET domain inhibitor anticancer agent. The article conveys some information:

A number of diazepines are known to inhibit bromo- and extra-terminal domain (BET) proteins. Their BET inhibitory activity derives from the fusion of an acetyl-lysine mimetic heterocycle onto the diazepine framework. Herein we describe a straightforward, modular synthesis of novel 1,2,3-triazolobenzodiazepines and show that the 1,2,3-triazole acts as an effective acetyl-lysine mimetic heterocycle. Structure-based optimization of this series of compounds led to the development of potent BET bromodomain inhibitors, e.g., I, with excellent activity against AF9-MLL-driven leukemic cells, concomitant with a reduction in c-MYC expression. These novel benzodiazepines therefore represent a promising class of therapeutic BET inhibitors.3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Recommanded Product: 844501-71-9) was used in this study.

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, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Recommanded Product: 844501-71-9

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

《A General Continuous Flow Method for Palladium catalysed Carbonylation Reactions Using Single and Multiple Tube-in-Tube Gas-Liquid Microreactors》 was published in European Journal of Organic Chemistry in 2014. These research results belong to Gross, Ulrike; Koos, Peter; O’Brien, Matthew; Polyzos, Anastasios; Ley, Steven V.. Application of 5952-93-2 The article mentions the following:

A series of amides [(ArC(O)NHR); Ar = 3-CH3C6H4; R = CH2CH2CH3, H2CC6H5, CH2CH:CH, etc.], esters [(R1C(O)OMe); R1 = 4-NO2C6H4, pyridin-2-yl, BrCH:CH, etc.] and carboxylic acids [(R2CO2H); R2 = 3-CH3C6H4, 4-NO2C6H4, 3-ClC6H4] by continuous flow chem. processes carbonylation of aryl and vinyl iodides and aryl bromides with a range of alkoxy, hydroxy and amino nucleophiles using palladium catalyst. Harnessing a semipermeable Teflon AF-2400 Tube-in-Tube assembly, these reactors permit the controlled transport of carbon monoxide into solution at elevated pressure to generate homogeneous flow streams, avoiding some potential issues associated with segmented flow gas-liquid reactors. As the volume of pressurized gas contained within the device is low, the hazards associated with this are potentially mitigated relative to comparable batch processes. It show how the incorporation of a second in-line gas-flow reactor allows for the sequential introduction of two gases (carbon monoxide and a gaseous nucleophile) into the reaction stream. In the experimental materials used by the author, we found Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2Application of 5952-93-2)

Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2) 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.Application of 5952-93-2

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

Product Details of 15366-34-4In 2022 ,《Discovery and Optimization of Highly Selective Inhibitors of CDK5》 was published in Journal of Medicinal Chemistry. The article was written by Daniels, Matthew H.; Malojcic, Goran; Clugston, Susan L.; Williams, Brett; Coeffet-Le Gal, Marie; Pan-Zhou, Xin-Ru; Venkatachalan, Srinivasan; Harmange, Jean-Christophe; Ledeboer, Mark. The article contains the following contents:

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic human disease, but to date, only one therapy (tolvaptan) is approved to treat kidney cysts in ADPKD patients. Cyclin-dependent kinase 5 (CDK5), an atypical member of the cyclin-dependent kinase family, has been implicated as a target for treating ADPKD. However, no compounds have been disclosed to date that selectively inhibit CDK5 while sparing the broader CDK family members. Herein, we report the discovery of CDK5 inhibitors, including GFB-12811 (I), that are highly selective over the other tested kinases. In cellular assays, our compounds demonstrate CDK5 target engagement while avoiding anti-proliferative effects associated with inhibiting other CDKs. In addition, we show that the compounds in this series exhibit promising in vivo PK profiles, enabling their use as tool compounds for interrogating the role of CDK5 in ADPKD and other diseases. After reading the article, we found that the author used Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Product Details of 15366-34-4)

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.Product Details of 15366-34-4

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

Application of 20154-03-4In 2021 ,《Metal-Free Direct Oxidative C-N Bond Coupling of Quinoxalin-2(1H)-ones with Azoles under Mild Conditions》 appeared in European Journal of Organic Chemistry. The author of the article were Guo, Jingwen; Zhang, Lina; Du, Xinyue; Zhang, Liting; Cai, Yuepiao; Xia, Qinqin. The article conveys some information:

Direct C3-H amination of quinoxalin-2(1H)-ones with azoles under mild conditions promoted by PIFA has been achieved in good yield in a very fast manner. Mechanistic study revealed that the reaction proceeds through a radical process. In addition, this method could be applied to gram-scale reaction.3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Application of 20154-03-4) was used in this study.

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.Application of 20154-03-4

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

Reference of Methyl 1H-pyrazole-3-carboxylateIn 1992 ,《Pyrazole-related nucleosides. Synthesis and antiviral/antitumor activity of some substituted pyrazole and pyrazolo[4,3-d]-1,2,3-triazin-4-one nucleosides》 appeared in Journal of Medicinal Chemistry. The author of the article were Manfredini, Stefano; Bazzanini, Rita; Baraldi, Pier Giovanni; Guarneri, Mario; Simoni, Daniele; Marongiu, Maria E.; Pani, Alessandra; La Colla, Paolo; Tramontano, Enzo. The article conveys some information:

Several pyrazole and pyrazolo[4,3-d]-1,2,3-triazin-4-oneribonucleosides, e.g. I (R = R1 = H; R = R1 = H, Me, R = Br, iodo, R1 = H) and II (R2 = Me, CMe3, CH2Ph), were prepared and tested for antiviral/antitumor activities. Appropriate heterocyclic bases were prepared by standard methodologies. All compounds were evaluated in vitro for cytostatic and antiviral activity. In the experiment, the researchers used many compounds, for example, Methyl 1H-pyrazole-3-carboxylate(cas: 15366-34-4Reference of 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.Reference of Methyl 1H-pyrazole-3-carboxylate

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

Application In Synthesis of 3-(Trifluoromethyl)-1H-pyrazoleIn 2010 ,《Selective angiotensin II AT2 receptor agonists with reduced CYP 450 inhibition》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Mahalingam, A. K.; Wan, Yiqian; Murugaiah, A. M. S.; Wallinder, Charlotta; Wu, Xiongyu; Plouffe, Bianca; Botros, Milad; Nyberg, Fred; Hallberg, Anders; Gallo-Payet, Nicole; Alterman, Mathias. The article conveys some information:

Structural alterations to the benzylic position of the first drug-like selective angiotensin II AT2 receptor agonist (1) have been performed, with the emphasis to reduce the CYP 450 inhibitory property of the initial structure. The imidazole moiety, responsible for the CYP 450 inhibitory effect in 1, was replaced with various heterocycles. In addition, the modes of attachment of the heterocycles, i.e., carbon vs. nitrogen attachment, and introduction of carbonyl functionalities to the benzylic position have been evaluated. In all the three series, AT2 receptor ligands with affinity in the lower nanomolar range were identified. None of the analogs, regardless of the substituents, exhibited any affinity for the AT1 receptor. Compounds with substantially reduced inhibition of the CYP 450 enzymes were obtained. Among them the compound 60 was found to induce neurite elongation in NG 108-15 cells and served as potent AT2 selective agonist.3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4Application In Synthesis of 3-(Trifluoromethyl)-1H-pyrazole) was used in this study.

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.Application In Synthesis of 3-(Trifluoromethyl)-1H-pyrazole

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