Category: pyrazoles-derivatives

Tsuno, Naoki; Yukimasa, Akira; Yoshida, Osamu; Suzuki, Shinji; Nakai, Hiromi; Ogawa, Tomoyuki; Fujiu, Motohiro; Takaya, Kenji; Nozu, Azusa; Yamaguchi, Hiroki; Matsuda, Hidetoshi; Funaki, Satoko; Yamanada, Natsue; Tanimura, Miki; Nagamatsu, Daiki; Asaki, Toshiyuki; Horita, Narumi; Yamamoto, Miyuki; Hinata, Mikie; Soga, Masahiko; Imai, Masayuki; Morioka, Yasuhide; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Iso, Yasuyoshi published the artcile< Pharmacological evaluation of novel (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives as TRPV4 antagonists for the treatment of pain>, Recommanded Product: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is TRPV4 antagonist analgesic pain; Ion channel; Pain; TRPV4 antagonist; Transient receptor potential vanilloid 4; Vanilloid receptor.

A novel series of (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives were identified as selective transient receptor potential vanilloid 4 (TRPV4) channel antagonist and showed analgesic effect in Freund’s Complete Adjuvant (FCA) induced mech. hyperalgesia model in guinea pig and rat. Modification of right part based on the compound I which was disclosed in the previous communication led to the identification of compound II as a flagship compound In this paper, the authors described the details about design, synthesis and structure-activity relationship (SAR) anal.

Bioorganic & Medicinal Chemistry published new progress about Analgesics. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Recommanded Product: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

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

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.

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.

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

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.

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.

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

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.

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.

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

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).

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.

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

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.

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.

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

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.

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.

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

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.

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.

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

Wijnberger, C.; Habraken, Clarisse L. published the artcile< Pyrazoles. VI. Electron-releasing capacity of the pyrazole ring>, Application In Synthesis of 17827-61-1, the main research area is pyrazoles electron releasing capacity.

Uv and 1H N.M.R. spectral data and C : O frequencies of some methylpyrazoles containing in the 3-, 4- or 5-position, a formyl-, acetyl- or ethoxycarbonyl group are reported. These data confirm earlier conclusions that, in particular, the 4-pyrazolyl group acts as an electron releasing group. The syntheses of a number of formyl-, acetyl- and ethoxycarbonyl pyrazoles are described. In addition, some 4-dicyanovinyl- and 4-tricvanovinylpyrazoles were investigated.

Journal of Heterocyclic Chemistry published new progress about 17827-61-1. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, Application In Synthesis of 17827-61-1.

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

Rajabzadeh, Maryam; Najdi, Nahid; Zarei, Zeinab; Khalifeh, Reza published the artcile< CuI Immobilized on Tricationic Ionic Liquid Anchored on Functionalized Magnetic Hydrotalcite (Fe3O4/HT-TIL-CuI) as a Novel, Magnetic and Efficient Nanocatalyst for Ullmann-Type C-N Coupling Reaction>, Application In Synthesis of 13788-92-6, the main research area is magnetic nanocatalyst hydrotalcite tricationic ionic liquid Ullmann type reaction.

One of the most important reactions in organic synthesis is Ullmann-type C-N coupling reaction which has been used for preparation of numerous biol. active compounds In this work, CuI immobilized on tricationic ionic liquid anchored on functionalized magnetic hydrotalcite (Fe3O4/HT-TIL-CuI) has been successfully prepared and fully characterized by different techniques, including fourier-transform IR spectroscopy, vibrating sample magnetometer, thermo gravimetric anal., transmission electron microscopy, field-emission SEM, energy dispersive X-ray spectroscopy, elemental mapping, zeta potential, X-ray diffraction, temperature programed desorption of ammonia (NH3-TPD), temperature-programmed reduction and inductively coupled plasma. The results showed that the as-prepared nanocatalyst possesses plate-like morphol. with approx. size of 50 nm and superparamagnetic behavior. Also, total acidity and total hydrogen consumption of the nanocatalyst were measured to be 8.5 and 1.41 mmol g-1, resp. This nanocatalyst exhibited favorable performance for C-N coupling reaction among a variety of aryl halides and N(H)-heterocycles (benzimidazoles, pyrazoles and triazoles) in the presence of 2.5 mol% of nanocatalyst without any additives under air atm. revealing high yields in all cases. Besides, it is noted that in the present system the desired product can be easily and quickly isolated and nanocatalyst also recovered magnetically from the reaction mixture employing a permanent magnet for at least six consecutive trials without a discernible decrease in catalytic activity which makes the proposed methodol. appropriate for industrial. The findings demonstrated the advantages of the present method as no need for neutral atm., appropriate times, recyclability of the catalyst, broad substrate scope, minimization of chem. waste, simple purification of products, easy workup process, and high yields.

Journal of Inorganic and Organometallic Polymers and Materials published new progress about Coupling reaction. 13788-92-6 belongs to class pyrazoles-derivatives, and the molecular formula is C9H7BrN2, Application In Synthesis of 13788-92-6.

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