Category: 847818-74-0

Formula: C10H17BN2O2In 2017 ,《A novel and efficient route for synthesis of Taladegib》 was published in Journal of Chemical Research. The article was written by Guo, Mingliang; Hong, Kwon Ho; Lv, Yongfeng; Ding, Yu; Li, Congcong; Xu, Hua; Qi, Wenxiu; Chen, Junqing; Ji, Min; Cai, Jin. The article contains the following contents:

Taladegib (LY-2940680), a small mol. Hedgehog signaling pathway inhibitor, was obtained from N-benzyl-4-piperidone via Borch reductive amination, acylation with 4-fluoro-2-(trifluoromethyl)benzoyl chloride, debenzylation, substitution with 1,4-dichlorophthalazine and Suzuki cross-coupling reaction with 1-methyl-1H-pyrazole-5-boronic acid. The advantages of this synthesis route were the elimination of Boc protection and deprotection and the inexpensive starting materials. Furthermore, the debenzylation reaction was achieved with simplified operational procedure using ammonium formate as hydrogen source that provided high reaction yield. This synthetic procedure was suitable for large-scale production of the compound for biol. evaluation and further study. 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: 847818-74-0Formula: 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. Formula: C10H17BN2O2

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

In 2014,Huang, Qinhua; Johnson, Ted W.; Bailey, Simon; Brooun, Alexei; Bunker, Kevin D.; Burke, Benjamin J.; Collins, Michael R.; Cook, Andrew S.; Cui, J. Jean; Dack, Kevin N.; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Johnson, Patrick S.; Kania, Robert S.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Li, Qiuhua; Lingardo, Laura; Liu, Wei; Lu, Melissa West; McTigue, Michele; Palmer, Cynthia L.; Richardson, Paul F.; Sach, Neal W.; Shen, Hong; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Tsaparikos, Konstantinos; Wang, Hui; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published 《Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib》.Journal of Medicinal Chemistry published the findings.SDS of cas: 847818-74-0 The information in the text is summarized as follows:

Crizotinib, an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS pos. patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine (I), which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclin. pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M). After reading the article, we found that the author used 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0SDS of cas: 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. SDS of cas: 847818-74-0

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

In 2017,King, Dalton; Iwuagwu, Christiana; Cook, Jim; McDonald, Ivar M.; Mate, Robert; Zusi, F. Christopher; Hill, Matthew D.; Fang, Haiquan; Zhao, Rulin; Wang, Bei; Easton, Amy E.; Miller, Regina; Post-Munson, Debra; Knox, Ronald J.; Gallagher, Lizbeth; Westphal, Ryan; Molski, Thaddeus; Fan, Jingsong; Clarke, Wendy; Benitex, Yulia; Lentz, Kimberley A.; Denton, Rex; Morgan, Daniel; Zaczek, Robert; Lodge, Nicholas J.; Bristow, Linda J.; Macor, John E.; Olson, Richard E. published 《BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia》.ACS Medicinal Chemistry Letters published the findings.HPLC of Formula: 847818-74-0 The information in the text is summarized as follows:

The therapeutic treatment of neg. symptoms and cognitive dysfunction associated with schizophrenia is a significant unmet medical need. Preclin. literature indicates that α7 neuronal nicotinic acetylcholine (nACh) receptor agonists may provide an effective approach to treating cognitive dysfunction in schizophrenia. The authors report herein the discovery and evaluation of I (BMS-933043), a novel and potent α7 nACh receptor partial agonist with high selectivity against other nicotinic acetylcholine receptor subtypes (>100-fold) and the 5-HT3A receptor (>300-fold). In vivo activity was demonstrated in a preclin. model of cognitive impairment, mouse novel object recognition. BMS-933043 has completed Phase I clin. trials.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) was used in this study.

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. HPLC of Formula: 847818-74-0

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

In 2014,Vara, Brandon A.; Mayasundari, Anand; Tellis, John C.; Danneman, Michael W.; Arredondo, Vanessa; Davis, Tyler A.; Min, Jaeki; Finch, Kristin; Guy, R. Kiplin; Johnston, Jeffrey N. published 《Organocatalytic, Diastereo- and Enantioselective Synthesis of Nonsymmetric cis-Stilbene Diamines: A Platform for the Preparation of Single-Enantiomer cis-Imidazolines for Protein-Protein Inhibition》.Journal of Organic Chemistry published the findings.Reference 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:

The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein-protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small mols. (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatog. separation using high-pressure liquid chromatog. (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsym. cis-stilbene diamines, e.g., I, and cis-imidazolines, e.g., II. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsym. cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate-catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chem. tools for disrupting protein-protein interactions. 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: 847818-74-0Reference 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, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, 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 2016,Zhang, Xiaojun; Glunz, Peter W.; Johnson, James A.; Jiang, Wen; Jacutin-Porte, Swanee; Ladziata, Vladimir; Zou, Yan; Phillips, Monique S.; Wurtz, Nicholas R.; Parkhurst, Brandon; Rendina, Alan R.; Harper, Timothy M.; Cheney, Daniel L.; Luettgen, Joseph M.; Wong, Pancras C.; Seiffert, Dietmar; Wexler, Ruth R.; Priestley, E. Scott published 《Discovery of a Highly Potent, Selective, and Orally Bioavailable Macrocyclic Inhibitor of Blood Coagulation Factor VIIa-Tissue Factor Complex》.Journal of Medicinal Chemistry published the findings.Recommanded Product: 847818-74-0 The information in the text is summarized as follows:

Inhibitors of the tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants, which show excellent efficacy and minimal bleeding in preclin. models. Starting with an aminoisoquinoline P1-based macrocyclic inhibitor, optimization of the P’ groups led to a series of highly potent and selective TF-FVIIa inhibitors, which displayed poor permeability. Fluorination of the aminoisoquinoline reduced the basicity of the P1 group and significantly improved permeability. The resulting lead compound I was highly potent, selective, and achieved good pharmacokinetics in dogs with oral dosing. Moreover, it demonstrated robust antithrombotic activity in a rabbit model of arterial thrombosis. 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: 847818-74-0Recommanded Product: 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. Recommanded Product: 847818-74-0

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

In 2017,Duret, Guillaume; Quinlan, Robert; Yin, Boyang; Martin, Rainer E.; Bisseret, Philippe; Neuburger, Markus; Gandon, Vincent; Blanchard, Nicolas published 《Intramolecular Inverse Electron-Demand [4 + 2] Cycloadditions of Ynamides with Pyrimidines: Scope and Density Functional Theory Insights》.Journal of Organic Chemistry published the findings.Application In Synthesis 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:

4-Aminopyridines are valuable scaffolds for the chem. industry in general, from life sciences to catalysis. We report herein a collection of structurally diverse polycyclic fused and spiro-4-aminopyridines that are prepared in only three steps from com. available pyrimidines. The key step of this short sequence is a [4 + 2]/retro-[4 + 2] cycloaddition between a pyrimidine and an ynamide, which constitutes the first examples of ynamides behaving as electron-rich dienophiles in [4 + 2] cycloaddition reactions. In addition, running the ihDA/rDA reaction in continuous mode in superheated toluene, to overcome the limited scalability of MW reactions, results in a notable production increase compared to batch mode. Finally, d. functional theory investigations shed light on the energetic and geometric requirements of the different steps of the ihDA/rDA sequence. 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 In Synthesis 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, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application In Synthesis 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 2016,Marx, Isaac E.; Dineen, Thomas A.; Able, Jessica; Bode, Christiane; Bregman, Howard; Chu-Moyer, Margaret; DiMauro, Erin F.; Du, Bingfan; Foti, Robert S.; Fremeau, Robert T.; Gao, Hua; Gunaydin, Hakan; Hall, Brian E.; Huang, Liyue; Kornecook, Thomas; Kreiman, Charles R.; La, Daniel S.; Ligutti, Joseph; Lin, Min-Hwa Jasmine; Liu, Dong; McDermott, Jeff S.; Moyer, Bryan D.; Peterson, Emily A.; Roberts, Jonathan T.; Rose, Paul; Wang, Jean; Youngblood, Beth D.; Yu, Violeta; Weiss, Matthew M. published 《Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement》.ACS Medicinal Chemistry Letters published the findings.Application of 847818-74-0 The information in the text is summarized as follows:

Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. The authors initially identified naphthalene sulfonamide 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (compound 3) as a potent and selective inhibitor of NaV1.7. Optimization to reduce biliary clearance by balancing hydrophilicity and hydrophobicity (Log D) while maintaining NaV1.7 potency led to the identification of quinazoline 16 (AM-2099). Compound 16 demonstrated a favorable pharmacokinetic profile in rat and dog and demonstrated dose-dependent reduction of histamine-induced scratching bouts in a mouse behavioral model following oral dosing. After reading the article, we found that the author used 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 2014,Johnson, Ted W.; Richardson, Paul F.; Bailey, Simon; Brooun, Alexei; Burke, Benjamin J.; Collins, Michael R.; Cui, J. Jean; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Huang, Qinhua; Kania, Robert S.; Kath, John C.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Lingardo, Laura; Liu, Wei; McTigue, Michele; Palmer, Cynthia L.; Sach, Neal W.; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. published 《Discovery of (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations》.Journal of Medicinal Chemistry published the findings.Quality Control 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:

Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-pos. non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and phys.-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clin. reported ALK kinase domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity. 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, antipyretic, neuroleptic, anticonvulsant, antiarrhythmic, sedative, muscle relaxant, monoamine oxidase inhibitory, anti-inflammatory, 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

Application of 847818-74-0In 2015 ,《Discovery of novel quinoline-based mTOR inhibitors via introducing intra-molecular hydrogen bonding scaffold (iMHBS): The design, synthesis and biological evaluation》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Ma, Xiaodong; Lv, Xiaoqing; Qiu, Ni; Yang, Bo; He, Qiaojun; Hu, Yongzhou. The article conveys some information:

A series of quinoline derivatives featuring the novelty of introducing intra-mol. hydrogen bonding scaffold (iMHBS) were designed, synthesized and biol. evaluated for their mTOR inhibitory activity, as well as anti-proliferative efficacies against HCT-116, PC-3 and MCF-7 cell lines. As a result, six compounds exhibited significant inhibition against mTOR with IC50 values below 35 nM. Hydrochloride of 4′-((4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)amino)-[3,6′-biquinoline]-3′-carboxamide (compound 15a), the most potent mTOR inhibitor reported herein (IC50 = 14 nM), also displayed the most favorable cellular activities, with the IC50 values of 0.46, 0.61 and 0.24 μM against HCT-116, PC-3 and MCF-7, resp. Besides, several compounds in this series were identified to be selective over class I PI3Ks. Further western blot anal. of 4′-((4-(4-acetylpiperazin-1-yl)-3-(trifluoromethyl)phe- nyl)amino)-[3,6′-biquinoline]-3′-carboxamide (compound 16b), a representative compound in this series, highlighted their advantage in surmounting the S6K/IRS1/PI3K neg. feedback loop upon dual inhibition of mTORC1 and mTORC2. In addition to the remarkable activity, (compound 15a) demonstrated acceptable stability in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and liver microsome, thereby being valuable for extensive in vivo investigation. In the experimental materials used by the author, we found 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

Category: pyrazoles-derivativesIn 2018 ,《Discovery of Reversible DNA Methyltransferase and Lysine Methyltransferase G9a Inhibitors with Antitumoral in Vivo Efficacy》 appeared in Journal of Medicinal Chemistry. The author of the article were Rabal, Obdulia; San Jose-Eneriz, Edurne; Agirre, Xabier; Sanchez-Arias, Juan Antonio; Vilas-Zornoza, Amaia; Ugarte, Ana; de Miguel, Irene; Miranda, Estibaliz; Garate, Leire; Fraga, Mario; Santamarina, Pablo; Fernandez Perez, Raul; Ordonez, Raquel; Saez, Elena; Roa, Sergio; Garcia-Barchino, Maria Jose; Martinez-Climent, Jose Angel; Liu, Yingying; Wu, Wei; Xu, Musheng; Prosper, Felipe; Oyarzabal, Julen. The article conveys some information:

Using knowledge- and structure-based approaches, we designed and synthesized reversible chem. probes that simultaneously inhibit the activity of two epigenetic targets, histone 3 lysine 9 methyltransferase (G9a) and DNA methyltransferases (DNMT), at nanomolar ranges. Enzymic competition assays confirmed our design strategy: substrate competitive inhibitors. Next, an initial exploration around our hit 11 was pursued to identify an adequate tool compound for in vivo testing. In vitro treatment of different hematol. neoplasia cell lines led to the identification of mols. with clear antiproliferative efficacies (GI50 values in the nanomolar range). On the basis of epigenetic functional cellular responses (levels of lysine 9 methylation and 5-methylcytosine), an acceptable therapeutic window (around 1 log unit) and a suitable pharmacokinetic profile, 12 was selected for in vivo proof-of-concept. Herein, 12 achieved a significant in vivo efficacy: 70% overall tumor growth inhibition of a human acute myeloid leukemia (AML) xenograft in a mouse model. 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: 847818-74-0Category: pyrazoles-derivatives)

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. Category: pyrazoles-derivatives

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