Category: pyrazoles-derivatives

Wang, Le; Doherty, George A.; Judd, Andrew S.; Tao, Zhi-Fu; Hansen, T. Matthew; Frey, Robin R.; Song, Xiaohong; Bruncko, Milan; Kunzer, Aaron R.; Wang, Xilu; Wendt, Michael D.; Flygare, John A.; Catron, Nathaniel D.; Judge, Russell A.; Park, Chang H.; Shekhar, Shashank; Phillips, Darren C.; Nimmer, Paul; Smith, Morey L.; Tahir, Stephen K.; Xiao, Yu; Xue, John; Zhang, Haichao; Le, Phuong N.; Mitten, Michael J.; Boghaert, Erwin R.; Gao, Wenqing; Kovar, Peter; Choo, Edna F.; Diaz, Dolores; Fairbrother, Wayne J.; Elmore, Steven W.; Sampath, Deepak; Leverson, Joel D.; Souers, Andrew James published the artcile< Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-XL Inhibitor>, HPLC of Formula: 936250-20-3, the main research area is tumor BCLXL BCL2 apoptosis A1155463 structure based drug design.

Herein we describe the discovery of A-1331852(I), a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL dependent tumor cells. This mol. was generated by re-engineering our previously reported BCL-XL inhibitor A-1155463 using structure-based drug design. Key design elements included rigidification of the A-1155463 pharmacophore and introduction of sp3-rich moieties capable of generating highly productive interactions within the key P4 pocket of BCL-XL. A-1331852 has since been used as a critical tool mol. for further exploring BCL-2 family protein biol., while also representing an attractive entry into a drug discovery program.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 936250-20-3 belongs to class pyrazoles-derivatives, and the molecular formula is C10H17BN2O2, HPLC of Formula: 936250-20-3.

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

Jeon, Dong Ju; Lee, Jung No; Kim, Hyoung Rae; Ryu, Eung K. published the artcile< The synthesis of a new pyrazolylimidazolinone via 1,3-dipolar cycloaddition reaction of N-methyl sydnone with methyl propiolate>, Product Details of C6H8N2O2, the main research area is pyrazolylimidazolinone preparation dipolar cycloaddition methylsydnone.

The preparation of 1-methyl-3-[4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-1H-pyrazole-4-carboxylic acid starting from N-methylsydnone and Me propiolate via a 1,3-dipolar cycloaddition reaction was reported.

Bulletin of the Korean Chemical Society published new progress about 1,3-Dipolar cycloaddition reaction. 17827-61-1 belongs to class pyrazoles-derivatives, and the molecular formula is C6H8N2O2, Product Details of C6H8N2O2.

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

Tu, Xing-Jun; Hao, Wen-Juan; Ye, Qin; Wang, Shuang-Shuang; Jiang, Bo; Li, Guigen; Tu, Shu-Jiang published the artcile< Four-Component Bicyclization Approaches to Skeletally Diverse Pyrazolo[3,4-b]pyridine Derivatives>, Synthetic Route of 118430-74-3, the main research area is pyrazolopyridine preparation; arylglyoxal aminopyrazole arylamine hydroxymethylpyranone cyclohexanedione four component cyclization.

A novel four-component bicyclization strategy has been established, allowing a flexible and practical approach to 37 examples of multicyclic pyrazolo[3,4-b]pyridines from low-cost and readily accessible arylglyoxals, pyrazol-5-amines, aromatic amines, 4-hydroxy-6-methyl-2H-pyran-2-one, and cyclohexane-1,3-diones. The polysubstituted cyclopenta[d]pyrazolo[3,4-b]pyridines were stereoselectively synthesized through a microwave-assisted special [3+2+1]/[3+2] bicyclization with good control of the spatial configuration of exocyclic double bonds. The novel [3+2+1]/[2+2+1] bicyclization resulted in 17 examples of unreported pyrazolo[3,4-b]pyrrolo[4,3,2-de]quinolones. Reasonable mechanisms for forming two new types of multicyclic pyrazolo[3,4-b]pyridines are also proposed.

Journal of Organic Chemistry published new progress about Acetals Role: RCT (Reactant), RACT (Reactant or Reagent) (arylglyoxals). 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Synthetic Route of 118430-74-3.

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

Teuscher, Kevin B.; Meyers, Kenneth M.; Wei, Qiangqiang; Mills, Jonathan J.; Tian, Jianhua; Alvarado, Joseph; Sai, Jiqing; Van Meveren, Mayme; South, Taylor M.; Rietz, Tyson A.; Zhao, Bin; Moore, William J.; Stott, Gordon M.; Tansey, William P.; Lee, Taekyu; Fesik, Stephen W. published the artcile< Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization>, Name: 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the main research area is cancers WDR5 WIN site inhibitor selectivity pharmacokinetic antiproliferative bioavailability.

WD repeat domain 5 (WDR5) is a nuclear scaffolding protein that forms many biol. important multiprotein complexes. The WIN site of WDR5 represents a promising pharmacol. target in a variety of human cancers. Here, we describe the optimization of our initial WDR5 WIN-site inhibitor using a structure-guided pharmacophore-based convergent strategy to improve its druglike properties and pharmacokinetic profile. The core of the previous lead remained constant while a focused SAR effort on the three pharmacophore units was combined to generate a new in vivo lead series. Importantly, this new series of compounds has picomolar binding affinity, improved cellular antiproliferative activity and selectivity, and increased kinetic aqueous solubility They also exhibit a desirable oral pharmacokinetic profile with manageable i.v. clearance and high oral bioavailability. Thus, these new leads including compound 41 (I), are useful probes toward studying the effects of WDR5 inhibition.

Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Name: 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

Ran, Kai; Zeng, Jun; Wan, Guoquan; He, Xiaojie; Feng, Zhanzhan; Xiang, Wang; Wei, Wei; Hu, Xiang; Wang, Ningyu; Liu, Zhihao; Yu, Luoting published the artcile< Design, synthesis and biological evaluations of a series of Pyrido[1,2-a]pyrimidinone derivatives as novel selective FGFR inhibitors>, Application of C11H19BN2O2, the main research area is pyridopyrimidinone preparation antitumor activity FGFR inhibitor; FGFR; Solubility; Tumor growth inhibition; pyrido[1,2-a]pyrimidinone.

Herein, the design and synthesis of pyrido[1,2-a]pyrimidinone derivatives I (R1 = methoxyethoxy, tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl, 1H-pyrazol-4-yl, etc.) and II (R2 = Me, azetidin-3-yl, etc.; R3 = 3-[(propan-2-yl)amino]propyl, prop-2-yn-1-yl, cyclopropylmethyl, etc.) as potent FGFR inhibitors were described. Examination of structure-activity relationships and preliminary assessment identified I (R1 = 1-methyl-1H-pyrazol-4-yl) as a novel FGFR inhibitor that displayed excellent potency in vitro. Candidate I [R1 = 1-methyl-1H-pyrazol-4-yl (III)] suppressed the phosphorylation of FGFR signaling pathways and induced cell cycle arrest and apoptosis at low nanomolar concentration In the kinase inhibition profile, III showed excellent kinase selectivity for the FGFR family. Furthermore, III showed higher aqueous solubility than Erdafitinib. Moreover, III exhibited potent antitumor activity (tumor growth inhibition = 106.4%) in FGFR2-amplified SNU-16 gastric cancer xenograft model using a daily oral dose of 30 mg/kg. These results suggest that III is a promising candidate for further drug development.

European Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 1046832-21-6 belongs to class pyrazoles-derivatives, and the molecular formula is C11H19BN2O2, Application of C11H19BN2O2.

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

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

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

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

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