Category: 844501-71-9

《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

Product Details of 844501-71-9In 2015 ,《Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Phillipson, Louisa J.; Segal, David H.; Nero, Tracy L.; Parker, Michael W.; Wan, Soo San; de Silva, Melanie; Guthridge, Mark A.; Wei, Andrew H.; Burns, Christopher J.. The article conveys some information:

The serine-threonine kinase CDK9 is a target of emerging interest for the development of anti-cancer drugs. There are multiple lines of evidence linking CDK9 activity to cancer, including the essential role this kinase plays in transcriptional regulation through phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. Indeed, inhibition of CDK9 has been shown to result in a reduction of short-lived proteins such as the pro-survival protein Mcl-1 in malignant cells leading to the induction of apoptosis. In this work we report our initial studies towards the discovery of selective CDK9 inhibitors, starting from the known multi-kinase inhibitor PIK-75 which possesses potent CDK9 activity. Our series is based on a pyrazolo[1,5-a]pyrimidine nucleus and, importantly, the resultant lead compound 18b is devoid of the structural liabilities present in PIK-75 and possesses greater selectivity. The results came from multiple reactions, including the reaction of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Product Details 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. Product Details of 844501-71-9

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

In 2012,Smith, Garry R.; Caglic, Dejan; Capek, Petr; Zhang, Yan; Godbole, Sujata; Reitz, Allen B.; Dickerson, Tobin J. published 《Reexamining hydroxamate inhibitors of botulinum neurotoxin serotype A: Extending towards the β-exosite》.Bioorganic & Medicinal Chemistry Letters published the findings.Application In Synthesis of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole The information in the text is summarized as follows:

Botulinum neurotoxins (BoNTs) are the most toxic proteins known to man, exposure to which results in flaccid paralysis. Given their extreme potency, these proteins have become studied as possible weapons of bioterrorism; however, effective treatments that function after intoxication have not progressed to the clinic. Here, we have reexamined one of the most effective inhibitors, 2,4-dichlorocinnamyl hydroxamate, in the context of the known plasticity of the BoNT/A light chain metalloprotease. Our studies have shown that modifications of this compound are tolerated and result in improved inhibitors, with the best compound having an IC50 of 0.23 μM. Given the inconsistency of structure-activity relationship trends observed across similar compounds, this data argues for caution in extrapolating across structural series. In addition to this study using 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, there are many other studies that have used 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Application In Synthesis of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole) 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, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. Application In Synthesis of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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

In 2010,Liu, Kevin K.-C.; Bagrodia, Shubha; Bailey, Simon; Cheng, Hengmiao; Chen, Hui; Gao, Lisa; Greasley, Samantha; Hoffman, Jacqui E.; Hu, Qiyue; Johnson, Ted O.; Knighton, Dan; Liu, Zhengyu; Marx, Matthew A.; Nambu, Mitchell D.; Ninkovic, Sacha; Pascual, Bernadette; Rafidi, Kristina; Rodgers, Caroline M.-L.; Smith, Graham L.; Sun, Shaoxian; Wang, Haitao; Yang, Anle; Yuan, Jing; Zou, Aihua published 《4-Methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors》.Bioorganic & Medicinal Chemistry Letters published the findings.Formula: C9H15BN2O2 The information in the text is summarized as follows:

Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a Me group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kα and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well. In the part of experimental materials, we found many familiar compounds, such as 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Formula: C9H15BN2O2)

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, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, antidiabetic and antibacterial activities. Formula: C9H15BN2O2

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

In 2014,Fukuzumi, Takeo; Aikawa, Haruo; Harada, Yasue; Sugai, Ayako; Murata, Asako; Nakatani, Kazuhiko published 《Synthesis of 8-substituted adenine and adenosine libraries and the binding to pre-miR-29a》.Bulletin of the Chemical Society of Japan published the findings.Application of 844501-71-9 The information in the text is summarized as follows:

A small chem. library of 8-substituted adenine and adenosine derivatives was synthesized and examined for binding to pre-miR-29a. We found that one compound showed the affinity with 61 nM of Kd and a 10-fold stronger binding than the double-stranded RNA.3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Application of 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. Application of 844501-71-9

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

Formula: C9H15BN2O2In 2016 ,《Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG》 was published in Bioorganic & Medicinal Chemistry Letters. The article was written by Huang, Shih-Chung; Adhikari, Sharmila; Afroze, Roushan; Brewer, Katherine; Calderwood, Emily F.; Chouitar, Jouhara; England, Dylan B.; Fisher, Craig; Galvin, Katherine M.; Gaulin, Jeffery; Greenspan, Paul D.; Harrison, Sean J.; Kim, Mi-Sook; Langston, Steven P.; Ma, Li-Ting; Menon, Saurabh; Mizutani, Hirotake; Rezaei, Mansoureh; Smith, Michael D.; Zhang, Dong Mei; Gould, Alexandra E.. The article contains the following contents:

Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein the authors describe the work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds I [R = H, Me2NCH2, MeNHCH2, etc.] have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo. In the experiment, the researchers used 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Formula: C9H15BN2O2)

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, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Formula: C9H15BN2O2

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

In 2015,Burdick, Daniel J.; Wang, Shumei; Heise, Christopher; Pan, Borlan; Drummond, Jake; Yin, JianPing; Goeser, Lauren; Magnuson, Steven; Blaney, Jeff; Moffat, John; Wang, Weiru; Chen, Huifen published 《Fragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors》.Bioorganic & Medicinal Chemistry Letters published the findings.Reference of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole The information in the text is summarized as follows:

A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine (compound 1) in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole mol. adjacent to (1) suggested a direction for fragment expansion. Structure-based core hopping applied to (1) led to 5H-pyrrolo[3,2-b]pyrazine that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core (I) was quickly optimized to 7-(1-benzyl-1H-pyrazol-4-yl)-2-(pyridin-4-yl)-5H-pyrrolo[3,2-b]pyrazine (compound 39) resulting in a greater than 6600-fold improvement in potency. In the part of experimental materials, we found many familiar compounds, such as 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9Reference of 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, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Reference of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

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

Recommanded Product: 844501-71-9In 2012 ,《Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families》 was published in Bioorganic & Medicinal Chemistry Letters. The article was written by Curtin, Michael L.; Frey, Robin R.; Heyman, H. Robin; Soni, Niru B.; Marcotte, Patrick A.; Pease, Lori J.; Glaser, Keith B.; Magoc, Terrance J.; Tapang, Paul; Albert, Daniel H.; Osterling, Donald J.; Olson, Amanda M.; Bouska, Jennifer J.; Guan, Zhiwen; Preusser, Lee C.; Polakowski, James S.; Stewart, Kent D.; Tse, Chris; Davidsen, Steven K.; Michaelides, Michael R.. The article contains the following contents:

In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the di-Ph urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clin. trials in solid and hematol. cancer populations.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, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities. Recommanded Product: 844501-71-9

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

In 2016,Wucherer-Plietker, Margarita; Merkul, Eugen; Mueller, Thomas J. J.; Esdar, Christina; Knoechel, Thorsten; Heinrich, Timo; Buchstaller, Hans-Peter; Greiner, Hartmut; Dorsch, Dieter; Finsinger, Dirk; Calderini, Michel; Bruge, David; Graedler, Ulrich published 《Discovery of novel 7-azaindoles as PDK1 inhibitors》.Bioorganic & Medicinal Chemistry Letters published the findings.COA of Formula: C9H15BN2O2 The information in the text is summarized as follows:

A combined screening strategy using HTS together with focused kinase library and virtual screening led to the identification of diverse chem. series as PDK1 inhibitors. The authors focused the medicinal chem. efforts on 7-azaindoles with low micromolar IC50s, e.g. I (IC50 = 1.1 μM) in the biochem. PDK1 assay. The structure-guided optimization efforts considered also PDK1 x-ray structures with weaker binding fragments and resulted in 7-azaindoles with significantly improved biochem. PDK1 potency in the two-digit nanomolar range. However, the most potent analogs only showed moderate activities in a cellular mechanistic assay, e.g. II (IC50 = 2.3 μM) together with either low microsomal stability or low permeability. The described structure-activity relationship together with PDK1 x-ray structures and early ADME data provided the basis for the subsequent hit-to-lead program. The experimental process involved the reaction of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 844501-71-9COA of Formula: C9H15BN2O2)

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. COA of Formula: C9H15BN2O2

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