pyrazoles-derivatives | Page 196 of 1033

Zhang, Hefeng’s team published research in Journal of Medicinal Chemistry in 2021-04-08 | 1046832-21-6

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Quality Control of 1046832-21-6.

Zhang, Hefeng; Peng, Xia; Dai, Yang; Shao, Jingwei; Ji, Yinchun; Sun, Yiming; Liu, Bo; Cheng, Xu; Ai, Jing; Duan, Wenhu published the artcile< Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor>, Quality Control of 1046832-21-6, the main research area is pyrimidinedione preparation receptor tyrosine kinase anticancer pharmacokinetic mol modeling.

The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used mol. modeling-assisted structural optimization starting with the low micromolar potency compound I to discover compound II, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that II could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound II significantly inhibited cellular Axl and Met signaling, suppressed Axl- and Met-driven cell proliferation, and restrained Gas6/Axl-mediated cancer cell migration or invasion. Furthermore, II exhibited significant antitumor efficacy in Axl-driven and Met-driven tumor xenograft models, causing tumor stasis or regression at well-tolerated doses. All these favorable data make II a promising therapeutic candidate for cancer treatment.

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

Browne, Duncan L’s team published research in Journal of the American Chemical Society in 2009-06-10 | 1002334-12-4

Journal of the American Chemical Society published new progress about [3+2] Cycloaddition reaction. 1002334-12-4 belongs to class pyrazoles-derivatives, and the molecular formula is C15H19BN2O2, Recommanded Product: 1-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Browne, Duncan L.; Vivat, Jerome F.; Plant, Andrew; Gomez-Bengoa, Enrique; Harrity, Joseph P. A. published the artcile< Investigation of the scope and regiochemistry of alkynylboronate cycloadditions with sydnones>, Recommanded Product: 1-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is sydnone alkynylboronate cycloaddition regioselective pyrazole boronate preparation; pyrazole boronate dioxaborolanyl preparation regioselective cycloaddition sydnone alkyne alkynylboronate; boronate pyrazolyl substituted preparation cycloaddition alkynylboronate; transition state structure regioselectivity cycloaddition alkynylboronate sydnone preparation pyrazolylboronate; potential energy surface regioselectivity cycloaddition alkynylboronate sydnone preparation pyrazolylboronate; optimized geometry sydnone alkynylboronate cycloaddition intermediate pyrazole transition state.

Di-, tri-, and tetrasubstituted 3- and 4-pyrazolylboronates were prepared by a convenient and highly regioselective procedure comprising cycloaddition of alkynylboronates to sydnones. Addition of 3-R1-4-R2-5-oxy-1,2,3-oxadiazolium with 2-alkynyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolanes R3CCB(OCMe2)2 in 1,2-dichlorobenzene at 180° gave 1-R1-3-R3-4-X-5-R2-1H-pyrazoles (20a-30a; X = 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl; R1 = Ph, Me, 4-NO2C6H4; R2 = Ph, Me, iPr; R3 = Ph, Me3Si); the corresponding regioisomers, 1-R1-4-R3-3-X-5-R2-1H-pyrazoles, were formed in less than 2% amounts However, regioselectivity (a:b) of the reaction of 3-Ph-5-oxy-1,2,3-oxadiazolium with R4CCB(OCMe2)2 giving 1-R1-3-R4-4-X- and 1-R1-4-R4-3-X-1H-pyrazoles (8a-13a, 8b-13b, resp., R1 = Ph, Me, PhCH2, R4 = H, Bu, Me3Si) was lower (1:7, 5:2 and 2:1, resp.). The origins of an observed regiochem. divergence in the reactions of terminal alkynylboronates with their more substituted analogs have been studied by DFT methods.

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

Wang, Huai-Wei’s team published research in Organic Letters in 2021-09-17 | 13788-92-6

Organic Letters published new progress about Anilines Role: RCT (Reactant), RACT (Reactant or Reagent). 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Recommanded Product: 1-(4-Bromophenyl)-1H-pyrazole.

Wang, Huai-Wei; Wu, Jia-Xue; Qiao, Yu-Han; Li, Yong-Fei; Li, Da-Cheng; Dou, Jian-Min; Yao, Qing-Xia; Lu, Yi published the artcile< RhIII-Catalyzed Direct Heteroarylation of C(sp3)-H and C(sp2)-H Bonds in Heterocycles with N-Heteroaromatic Boronates>, Recommanded Product: 1-(4-Bromophenyl)-1H-pyrazole, the main research area is methyl quinoline heteroaryl boronate rhodium catalyst heteroarylation; heteroaryl methyl quinoline preparation; phenyl pyridine heteroaryl boronate rhodium catalyst heteroarylation; heteroaromatic phenyl pyridine preparation.

A RhIII-catalyzed heteroarylation of C(sp3)-H and C(sp2)-H bonds in heterocycles with organoboron reagents were disclosed. This protocol displayed high efficiency and excellent functional group tolerance. A range of heterocyclic boronates with strong coordinating atoms, including pyridine, pyrimidine, pyrazole, thiophene and furan derivatives, extensively served as the coupling reagents. The direct heteroarylation method could supply potential application in terms of the synthesis of drug mols. with multiple heterocycles.

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

Huang, Qinhua’s team published research in Journal of Medicinal Chemistry in 2014-02-27 | 936250-20-3

Journal of Medicinal Chemistry published new progress about Antitumor agents. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Electric Literature of 936250-20-3.

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 the artcile< Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib>, Electric Literature of 936250-20-3, the main research area is crizotinib resistant lymphoma kinase mutation inhibitor preparation SAR.

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).

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

Chen, Ying-Chu’s team published research in Bioconjugate Chemistry in 2020-03-18 | 118430-74-3

Bioconjugate Chemistry published new progress about Anilines Role: CMB (Combinatorial Study), RCT (Reactant), RACT (Reactant or Reagent). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Application of C7H11N3.

Chen, Ying-Chu; Faver, John C.; Ku, Angela F.; Miklossy, Gabriella; Riehle, Kevin; Bohren, Kurt M.; Ucisik, Melek N.; Matzuk, Martin M.; Yu, Zhifeng; Simmons, Nicholas published the artcile< C-N Coupling of DNA-Conjugated (Hetero)aryl Bromides and Chlorides for DNA-Encoded Chemical Library Synthesis>, Application of C7H11N3, the main research area is DNA encoded heteroaryl amide library synthesis.

DNA-encoded chem. library (DECL) screens are a rapid and economical tool to identify chem. starting points for drug discovery. As a robust transformation for drug discovery, palladium-catalyzed C-N coupling is a valuable synthetic method for the construction of DECL chem. matter; however, currently disclosed methods have only been demonstrated on DNA-attached (hetero)aromatic iodide and bromide electrophiles. We developed conditions utilizing an N-heterocyclic carbene-palladium catalyst that extends this reaction to the coupling of DNA-conjugated (hetero)aromatic chlorides with (hetero)aromatic and select aliphatic amine nucleophiles. In addition, we evaluated steric and electronic effects within this catalyst series, carried out a large substrate scope study on two representative (hetero)aryl bromides, and applied this newly developed method within the construction of a 63 million-membered DECL.

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

Ochiai, Hiroshi’s team published research in Chemical & Pharmaceutical Bulletin in 2004-09-30 | 118430-74-3

Chemical & Pharmaceutical Bulletin published new progress about Anti-inflammatory agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, COA of Formula: C7H11N3.

Ochiai, Hiroshi; Ishida, Akiharu; Ohtani, Tazumi; Kusumi, Kensuke; Kishikawa, Katuya; Yamamoto, Susumu; Takeda, Hiroshi; Obata, Takaaki; Nakai, Hisao; Toda, Masaaki published the artcile< Discovery of new orally active phosphodiesterase (PDE4) inhibitors>, COA of Formula: C7H11N3, the main research area is phosphodiesterase PDE4 inhibitor discovery oral antiinflammatory; anilinopyrazolopyridine derivative preparation PDE4 inhibiting structure subtype selectivity.

A series of 4-anilinopyrazolopyridine derivatives were synthesized and biol. evaluated as inhibitors of phosphodiesterase (PDE4). Chem. modification of 3, a structurally new chem. lead that was found in our inhouse library, was focused on 1- and 3-substituents. Full details of the discovery of a new orally active chem. lead 5 are presented. Structure-activity relationship data, pharmacol. evaluation, and the subtype selectivity study are also presented.

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

Yu, Mingfeng’s team published research in European Journal of Medicinal Chemistry in 2021-03-15 | 1002334-12-4

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 1002334-12-4 belongs to class pyrazoles-derivatives, and the molecular formula is C15H19BN2O2, Reference of 1002334-12-4.

Yu, Mingfeng; Teo, Theodosia; Yang, Yuchao; Li, Manjun; Long, Yi; Philip, Stephen; Noll, Benjamin; Heinemann, Gary K.; Diab, Sarah; Eldi, Preethi; Mekonnen, Laychiluh; Anshabo, Abel T.; Rahaman, Muhammed H.; Milne, Robert; Hayball, John D.; Wang, Shudong published the artcile< Potent and orally bioavailable CDK8 inhibitors: Design, synthesis, structure-activity relationship analysis and biological evaluation>, Reference of 1002334-12-4, the main research area is pyridine preparation structure activity relationship biol evaluation CDK8 inhibitor; CDK8 inhibitor; Drug-like properties; Pharmacokinetics; Structure-activity relationship; Toxicity.

CDK8 regulates transcription either by phosphorylation of transcription factors or, as part of a four-subunit kinase module, through a reversible association of the kinase module with the Mediator complex, a highly conserved transcriptional coactivator. Deregulation of CDK8 has been found in various types of human cancer, while the role of CDK8 in suppressing anti-cancer response of natural killer cells is being understood. Currently, CDK8-targeting cancer drugs are highly sought-after. Herein authors detail the discovery of a series of novel pyridine-derived CDK8 inhibitors. Medicinal chem. optimization gave rise to I (AU1-100), a potent CDK8 inhibitor with oral bioavailability. The compound inhibited the proliferation of MV4-11 acute myeloid leukemia cells with the kinase activity of cellular CDK8 dampened. No systemic toxicol. was observed in the mice treated with I. These results warrant further pre-clin. studies of I as an anti-cancer agent.

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

Zhang, Lingtian’s team published research in Journal of Medicinal Chemistry in 2022 | CAS: 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. Application of 930-36-9

Zhang, Lingtian; Moccia, Marialuisa; Briggs, David C.; Bharate, Jaideep B.; Lakkaniga, Naga Rajiv; Knowles, Phillip; Yan, Wei; Tran, Phuc; Kharbanda, Anupreet; Wang, Xiuqi; Leung, Yuet-Kin; Frett, Brendan; Santoro, Massimo; McDonald, Neil Q.; Carlomagno, Francesca; Li, Hong-yu published an article on January 27 ,2022. The article was titled 《Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose》, and you may find the article in Journal of Medicinal Chemistry.Application of 930-36-9 The information in the text is summarized as follows:

Mutations of the rearranged during transfection (RET) kinase are frequently reported in cancer, which make it as an attractive therapeutic target. Herein, we discovered a series of N-trisubstituted pyrimidine derivatives as potent inhibitors for both wild-type (weight) RET and RETV804M, which is a resistant mutant for several FDA-approved inhibitors. The X-ray structure of a representative inhibitor with RET revealed that the compound binds in a unique pose that bifurcates beneath the P-loop and confirmed the compound as a type I inhibitor. Through the structure-activity relationship (SAR) study, compound 20 (I) was identified as a lead compound, showing potent inhibition of both RET and RETV804M. Addnl., compound 20 displayed potent antiproliferative activity of CCDC6-RET-driven LC-2/ad cells. Anal. of RET phosphorylation indicated that biol. activity was mediated by RET inhibition. Collectively, N-trisubstituted pyrimidine derivatives could serve as scaffolds for the discovery and development of potent inhibitors of type I RET and its gatekeeper mutant for the treatment of RET-driven cancers. The results came from multiple reactions, including the reaction of 1-Methylpyrazole(cas: 930-36-9Application of 930-36-9)

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

Ul′yanovskii, Nikolay V.’s team published research in Microchemical Journal in 2021 | CAS: 930-36-9

Ul′yanovskii, Nikolay V.; Kosyakov, Dmitry S.; Popov, Mark S.; Shavrina, Irina S.; Ivakhnov, Artem D.; Kenessov, Bulat; Lebedev, Albert T. published their research in Microchemical Journal on December 31 ,2021. The article was titled 《Rapid quantification and screening of nitrogen-containing rocket fuel transformation products by vortex assisted liquid-liquid microextraction and gas chromatography – high-resolution Orbitrap mass spectrometry》.Safety of 1-Methylpyrazole The article contains the following contents:

Existing and newly developed technologies for clean-up of wastewaters and soils contaminated with rocket fuel unsym. dimethylhydrazine (UDMH) are based on the oxidative treatment, as well as gasification in supercritical water. Being easily transformed by a radical mechanism, UDMH is capable of producing an extremely wide range of potentially hazardous nitrogen-containing products. Their identification and simultaneous quantification at low concentrations in water samples by gas chromatog. is a challenging task requiring a matrix change. We proposed a combination of dispersive vortex-assisted liquid-liquid microextraction (VALLME) of analytes followed by gas chromatog. – Orbitrap mass spectrometry allowing simultaneous target anal. and non-targeted screening. Dichloromethane and chloroform provided rapid (10 min) and effective extraction of most of UDMH transformation products. The maximum recoveries were achieved by alkalizing and saturating the aqueous samples with ammonium sulfate. The use of pyridine-d5 as an internal standard allowed developing an approach to the simultaneous determination of 24 compounds of various classes with detection limits for the most analytes in the range 0.02-1.1 μg L-1 and accuracy of 81-117% with low-cost, simple, and rapid sample preparation procedure. Extraction with a 100 μL of chloroform allowed further increasing sensitivity up to one order of magnitude and attaining LOD values for 20 compounds in the range of 0.002-0.1 μg L-1 comparable with that obtained by vacuum-assisted headspace solid-phase microextraction The developed method was validated and tested for the analyses of real samples – degraded aqueous solution of rocket fuel, products of UDMH treatment in supercritical water and aqueous extract of soil from the place of carrier rocket accidental crash. Twenty-nine compounds that were not previously described as UDMH transformation products were tentatively identified.1-Methylpyrazole(cas: 930-36-9Safety of 1-Methylpyrazole) was used in this study.

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

Kumar, Sanjeev’s team published research in Journal of Medicinal Chemistry in 2019 | CAS: 5952-93-2

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

Kumar, Sanjeev; Waldo, Jesse P.; Jaipuri, Firoz A.; Marcinowicz, Agnieszka; Van Allen, Clarissa; Adams, James; Kesharwani, Tanay; Zhang, Xiaoxia; Metz, Richard; Oh, Angela J.; Harris, Seth F.; Mautino, Mario R. published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1》.Recommanded Product: Methyl 1-methyl-1H-pyrazole-4-carboxylate The author mentioned the following in the article:

A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacol. properties. Suitably placed hydrophobic and polar functional groups in the lead mol. allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties. In the experiment, the researchers used many compounds, for example, Methyl 1-methyl-1H-pyrazole-4-carboxylate(cas: 5952-93-2Recommanded Product: Methyl 1-methyl-1H-pyrazole-4-carboxylate)

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