pyrazoles-derivatives

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

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

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

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

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

Chowdhury, Sarwat; Chen, Yen Ting; Fang, Xingang; Grant, Wayne; Pocas, Jennifer; Cameron, Michael D.; Ruiz, Claudia; Lin, Li; Park, HaJeung; Schroter, Thomas; Bannister, Thomas D.; LoGrasso, Philip V.; Feng, Yangbo published the artcile< Amino acid derived quinazolines as Rock/PKA inhibitors>, Name: 3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is amino acid derived quinazolinone Rock PKA inhibitor.

SAR and lead optimization studies for Rock inhibitors based on amino acid-derived quinazolines are described. Studies demonstrated that these amino acid derived quinazolinones were mainly puromycin aminonucleoside (PAN)-Rho-associated protein kinase (Rock) (I & II) inhibitors. While selectivity against other kinases could be achieved, selectivity for most of these compounds against PKA was not achieved. This is distinct from Rock inhibitors based on non-amino acid derived quinazolinones, where high selectivity against PKA could be obtained.22 The inhibitors presented here in some cases possessed sub-nanomolar inhibition of Rock, nanomolar potency in ppMLC cell based assays, low to fair cytochrome P 450 inhibition, and good human microsomal stability.

Bioorganic & Medicinal Chemistry Letters published new progress about Heteroarylation (Suzuki). 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, Name: 3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

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

Kobe, Joze; Robins, Roland K.; O’Brien, Darrell E. published the artcile< Synthesis and chemical reactions of certain pyrazolo[1,5-a]-1,3,5-triaziness>, Product Details of C6H5ClN4S, the main research area is pyrazolotriazine; adenine analog pyrazolotriazine; hypoxanthine analog pyrazolotriazine; xanthine analog pyrazolotriazine; substitution pyrazolotriazine.

3-Aminopyrazole was used to prepare pyrazolo[1,5-a]-1,3,5-triazines. 4-Chloro-2-methylthiopyrazolo[1,5-a]-1,3,5-triazine was prepared and used for studies of nucleophilic displacement reactions; both the Cl and MeS groups may be displaced by nucleophiles. Adenine, hypoxanthine, and xanthine analogs of the pyrazolo[1,5-a]-1,3,5-triazine ring were prepared similarly. Electrophilic substitution occurs at C-8. The Me group was introduced at C-4 by a novel ring opening and closing of the triazine ring.

Journal of Heterocyclic Chemistry published new progress about Substitution reaction. 54346-19-9 belongs to class pyrazoles-derivatives, and the molecular formula is C6H5ClN4S, Product Details of C6H5ClN4S.

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

Westaway, Susan M.; Preston, Alex G. S.; Barker, Michael D.; Brown, Fiona; Brown, Jack A.; Campbell, Matthew; Chung, Chun-wa; Drewes, Gerard; Eagle, Robert; Garton, Neil; Gordon, Laurie; Haslam, Carl; Hayhow, Thomas G.; Humphreys, Philip G.; Joberty, Gerard; Katso, Roy; Kruidenier, Laurens; Leveridge, Melanie; Pemberton, Michelle; Rioja, Inma; Seal, Gail A.; Shipley, Tracy; Singh, Onkar; Suckling, Colin J.; Taylor, Joanna; Thomas, Pamela; Wilson, David M.; Lee, Kevin; Prinjha, Rab K. published the artcile< Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives>, Related Products of 1046832-21-6, the main research area is pyrido pyrimidinone derivative preparation histone lysine demethylase KDM4 inhibitor.

Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochem. and target-specific, cellular mechanistic assays.

Journal of Medicinal Chemistry published new progress about Histone lysine demethylase inhibitors. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Related Products of 1046832-21-6.

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

Mammoliti, Oscar; Palisse, Adeline; Joannesse, Caroline; El Bkassiny, Sandy; Allart, Brigitte; Jaunet, Alex; Menet, Christel; Coornaert, Beatrice; Sonck, Kathleen; Duys, Inge; Clement-Lacroix, Philippe; Oste, Line; Borgonovi, Monica; Wakselman, Emanuelle; Christophe, Thierry; Houvenaghel, Nicolas; Jans, Mia; Heckmann, Bertrand; Saniere, Laurent; Brys, Reginald published the artcile< Discovery of the S1P2 Antagonist GLPG2938 (1-[2-Ethoxy-6-(trifluoromethyl)-4-pyridyl]-3-[[5-methyl-6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]pyridazin-3-yl]methyl]urea), a Preclinical Candidate for the Treatment of Idiopathic Pulmonary Fibrosis>, Related Products of 1046832-21-6, the main research area is S1PR2 antagonist idiopathic pulmonary fibrosis GLPG2938.

Mounting evidence from the literature suggests that blocking S1P2 receptor (S1PR2) signaling could be effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, only a few antagonists have been so far disclosed. A chem. enablement strategy led to the discovery of a pyridine series with good antagonist activity. A pyridazine series with improved lipophilic efficiency and with no CYP inhibition liability was identified by scaffold hopping. Further optimization led to the discovery of 40 (GLPG2938)(I), a compound with exquisite potency on a phenotypic IL8 release assay, good pharmacokinetics, and good activity in a bleomycin-induced model of pulmonary fibrosis.

Journal of Medicinal Chemistry published new progress about Drug design. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Related Products of 1046832-21-6.

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

Pascanu, Vlad; Hansen, Peter R.; Bermejo Gomez, Antonio; Ayats, Carles; Platero-Prats, Ana E.; Johansson, Magnus J.; Pericas, Miquel A.; Martin-Matute, Belen published the artcile< Highly Functionalized Biaryls via Suzuki-Miyaura Cross-Coupling Catalyzed by Pd@MOF under Batch and Continuous Flow Regimes>, COA of Formula: C11H19BN2O2, the main research area is biaryl preparation green chem; arylboronic acid aryl halide Suzuki Miyaura flow chem microwave; palladium nanoparticle metal organic framework catalyst; MOF catalysis; flow chemistry; heterocycles; suzuki-miyaura.

A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki-Miyaura cross-coupling reaction catalyzed by Pd nanoparticles supported in a functionalized mesoporous MOF (8 wt % Pd@MIL-101(Cr)-NH2). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted mols. are important intermediates in the synthesis of pharmaceuticals and the versatility of this catalytic system is exemplified, which affords better yields than currently existing com. procedures. Most importantly, Pd@MIL-101-NH2 was packed in a micro-flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chem. for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large-scale applications.

ChemSusChem published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, COA of Formula: C11H19BN2O2.

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