37622-90-5 | pyrazoles-derivatives

Zhang, Yuan team published research in Chinese Chemical Letters in 2021 | 37622-90-5

37622-90-5, Ethyl 4-pyrazolecarboxylate, also known as Ethyl pyrazole-4-carboxylate, is a useful research compound. Its molecular formula is C6H8N2O2 and its molecular weight is 140.14 g/mol. The purity is usually 95%.

Ethyl pyrazole-4-carboxylate is a low yield, transition metal salt that is used in the synthesis of pyrazoles. It can be synthesized by the reaction of sodium ethoxide with ethyl chloroformate and a Grignard reagent. Sodium ethoxide is added to a suspension of sodium chloride and dried ethyl chloroformate, followed by addition of magnesium turnings. The mixture is refluxed for one hour, cooled, and filtered to give crystals. Ethyl pyrazole-4-carboxylate is used in the preparation of ethyl esters from aliphatic alcohols by reacting with boron trichloride or phosphorus pentachloride. It participates in certain chemical reactions as a byproduct and can damage equipment during chemical reactions. The yield of this compound can be increased by using an excess amount of Grignard reagent or adding hexamethylenetetramine to the reaction mixture, Synthetic Route of 37622-90-5

Pyrazoles are synthesized by the reaction of α,β-unsaturated aldehydes with hydrazine and subsequent dehydrogenation. 37622-90-5, formula is C6H8N2O2, Name is Ethyl 4-pyrazolecarboxylate. Substituted pyrazoles are prepared by condensation of 1,3-diketones with hydrazine (Knorr-type reactions). For example, acetylacetone and hydrazine gives 3,5-dimethylpyrazole. Synthetic Route of 37622-90-5.

Zhang, Yuan;Luo, Han;Lu, Qixing;An, Qiaoyu;Li, You;Li, Shanshan;Tang, Zongyuan;Li, Baosheng research published 《 Access to pyridines via cascade nucleophilic addition reaction of 1,2,3-triazines with activated ketones or acetonitriles》, the research content is summarized as follows. The cascade nucleophilic addition reactions of 1,2,3-triazines with activated acetonitriles or ketones, which were used to construct highly substituted pyridines that were not easily accessed by conventional methods was reported. The strategy addressed some structural diversity issues currently facing medicinal chem., and the resulting pyridines was used as convenient precursors for the synthesis of related pharmaceuticals. This method was applied to the syntheses of the marketed drug etoricoxib and several biol. important mols. in a few steps.

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

Zhao, Lulu team published research in Organic Letters in 2022 | 37622-90-5

Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns. 37622-90-5, formula is C6H8N2O2, Name is Ethyl 4-pyrazolecarboxylate. 1-Methyl-5-(trifluoromethyl)pyrazole underwent deprotonation and subsequent carboxylation mainly or exclusively at either the 4-position of the heterocycle or at the nitrogen-attached methyl group. Related Products of 37622-90-5.

Zhao, Lulu;Zhong, Qiwen;Tian, Jian;Luo, Mengqi;Yang, Chao;Guo, Lin;Xia, Wujiong research published 《 Electrochemical Synthesis of β-Functionalized Ketones via Ring-Opening of Cycloalkanols》, the research content is summarized as follows. The electrochem. deconstructive functionalization of cycloalkanols with nucleophiles was studied, which allowed functionalization to occur exclusively at the β-position of ketones. The substrate scope includes a wide range of cycloalkanols as well as diverse N, O, C and P-centered nucleophiles, providing ready access to β-functionalized ketones as products. Mechanistic studies support the generation of α,β-unsaturated ketones as key intermediates followed by Michael addition with nucleophiles.

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

Zheng, Ke team published research in Journal of Medicinal Chemistry in 2014 | 37622-90-5

Zheng, Ke;Iqbal, Sarah;Hernandez, Pamela;Park, HaJeung;LoGrasso, Philip V.;Feng, Yangbo research published 《 Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives》, the research content is summarized as follows. The c-jun N-terminal kinase 3 (JNK3) is expressed primarily in the brain. Numerous reports have shown that inhibition of JNK3 is a promising strategy for treatment of neurodegeneration. The optimization of aminopyrazole-based JNK3 inhibitors with improved potency, isoform selectivity, and pharmacol. properties by structure-activity relationship (SAR) studies utilizing biochem. and cell-based assays, and structure-based drug design is reported. These inhibitors had high selectivity over JNK1 and p38α, minimal cytotoxicity, potent inhibition of 6-OHDA-induced mitochondrial membrane potential dissipation and ROS generation, and good drug metabolism and pharmacokinetic (DMPK) properties for iv dosing. 26n was profiled against 464 kinases and was found to be highly selective hitting only seven kinases with >80% inhibition at 10 μM. Moreover, 26n showed good solubility, good brain penetration, and good DMPK properties. Finally, the crystal structure of 26k in complex with JNK3 was solved at 1.8 Å to explore the binding mode of aminopyrazole based JNK3 inhibitors.

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

Zheng, Ke team published research in Journal of Medicinal Chemistry in 2016 | 37622-90-5

Name: Ethyl 4-pyrazolecarboxylate, Ethyl 4-pyrazolecarboxylate, also known as Ethyl pyrazole-4-carboxylate, is a useful research compound. Its molecular formula is C6H8N2O2 and its molecular weight is 140.14 g/mol. The purity is usually 95%.

Zheng, Ke;Iqbal, Sarah;Hernandez, Pamela;Park, HaJeung;LoGrasso, Philip V.;Feng, Yangbo research published 《 Correction to Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives [Erratum to document cited in CA162:029776]》, the research content is summarized as follows. On page S4, Section 2.1, Line 1 of the supporting Inforamtion is incorrect; The correct information is given.

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

Zhou, Qifan team published research in Journal of Organic Chemistry in 2019 | 37622-90-5

Computed Properties of 37622-90-5, Ethyl 4-pyrazolecarboxylate, also known as Ethyl pyrazole-4-carboxylate, is a useful research compound. Its molecular formula is C6H8N2O2 and its molecular weight is 140.14 g/mol. The purity is usually 95%.

Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. 37622-90-5, formula is C6H8N2O2, Name is Ethyl 4-pyrazolecarboxylate. Pyrazoles are a class of compounds that have the ring C3N2 with adjacent nitrogen atoms.Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol. Computed Properties of 37622-90-5.

Zhou, Qifan;Du, Fangyu;Chen, Yuanguang;Fu, Yang;Sun, Wenjiao;Wu, Ying;Chen, Guoliang research published 《 L-(-)-Quebrachitol as a Ligand for Selective Copper(0)-Catalyzed N-Arylation of Nitrogen-Containing Heterocycles》, the research content is summarized as follows. L-(-)-Quebrachitol (QCT) was found as a ligand of copper powder for selective N-arylation of nitrogen-containing heterocycles with aryl halides. Furthermore, another potential catalytic system (copper powder/QCT/t-BuOK) was successfully adapted to unactivated aryl chlorides.

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

Zou, Yiquan team published research in European Journal of Medicinal Chemistry in 2013 | 37622-90-5

HPLC of Formula: 37622-90-5, Ethyl 4-pyrazolecarboxylate, also known as Ethyl pyrazole-4-carboxylate, is a useful research compound. Its molecular formula is C6H8N2O2 and its molecular weight is 140.14 g/mol. The purity is usually 95%.

Zou, Yiquan;Xu, Lei;Chen, Wuyan;Zhu, Yiping;Chen, Tiantian;Fu, Yan;Li, Li;Ma, Lanping;Xiong, Bing;Wang, Xin;Li, Jian;He, Jianhua;Zhang, Haiyan;Xu, Yechun;Li, Jia;Shen, Jingkang research published 《 Discovery of pyrazole as C-terminus of selective BACE1 inhibitors》, the research content is summarized as follows. We recently discovered and reported dual inhibitor 5 of AChE and BACE1 with N-benzylpiperidine Et as C-terminus. Compound 5 showed potent inhibitory activities for BACE1, and could reduce endogenous Aβ_1-40 production in APP transgenic mice. In present work, we rapidly identified substituted triazole as the C-terminus of compound 5 by replacing the benzylpiperidine Et group with click chem. and tested these synthesized compounds by in situ screening assay. As revealed by the crystal structures of BACE1 in complex with our triazole compound 12, we found that Pro70 and Thr72 located in the flap region were the critical components for binding with these inhibitors. With the aid of the crystal structure, a new series of five-membered heterocyclic compounds was prepared in order to explore the structure-activity relationship (SAR) of this class of mols. From these efforts, pyrazole was discovered as a novel C-terminus of BACE1 inhibitors. After further modification of pyrazole with variable substituents, compound 37 exhibited good potency in enzyme inhibition assay (IC₅₀ = 0.025 μM) and compound 33 showed moderate inhibition effects on Aβ production of APP transfected HEK293 cells. Moreover, these pyrazole derivatives demonstrated good selectivity vs. cathepsin D. Our results indicated that the vicinity of Pro70 and Thr72 might be utilized as a subsite, and the discovered pyrazole derivatives might provide useful hints for developing novel BACE1 inhibitors as anti-AD drugs.

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

Ye, Fei team published research in Nature Communications in 2021 | 37622-90-5

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. 37622-90-5, formula is C6H8N2O2, Name is Ethyl 4-pyrazolecarboxylate. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. Recommanded Product: Ethyl 4-pyrazolecarboxylate.

Ye, Fei;Ge, Yao;Spannenberg, Anke;Neumann, Helfried;Xu, Li-Wen;Beller, Matthias research published 《 3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents》, the research content is summarized as follows. The synthesis of 3,3-difluoropropen-1-yl ammonium salts (DFPAs) (F)₂C=CHCH₂N⁺(R)(R₁)R₂.^–OTf [R = Me, 4-chorophenyl, 4-trimethylsilylphenyl, etc.; R¹ = Et, n-Bu; R² = Me, Et; R¹R² = -(CH₂)₅-, -(CH₂)₄-, -(CH₂)₂O(CH₂)₂-] as stable, and scalable gem-difluoromethylation reagents, which allow for the direct reaction with a wide range of fascinating nucleophiles e.g., [1,1′-biphenyl]-4-ol was presented. DFPAs smoothly react with N-, O-, S-, Se-, and C-nucleophiles under mild conditions without necessity of metal catalysts with exclusive regioselectivity. In this way, the presented reagents also permit the straightforward preparation of many analogs of existing pharmaceuticals.

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

Ye, Jiqing team published research in Pharmaceuticals in 2021 | 37622-90-5

Category: pyrazoles-derivatives, Ethyl 4-pyrazolecarboxylate, also known as Ethyl pyrazole-4-carboxylate, is a useful research compound. Its molecular formula is C6H8N2O2 and its molecular weight is 140.14 g/mol. The purity is usually 95%.

Ye, Jiqing;Lin, Lin;Xu, Jinyi;Chan, Paul Kay-sheung;Yang, Xiao;Ma, Cong research published 《 Design, synthesis, biological evaluation and in silico studies of pyrazole-based NH₂-acyl oseltamivir analogues as potent neuraminidase inhibitors》, the research content is summarized as follows. Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an addnl. binding pocket, and novel NA inhibitors were designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH₂-acyl derivatives, e.g., I of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Addnl., mol. docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.

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

Yin, Yuan team published research in Bioorganic & Medicinal Chemistry in 2019 | 37622-90-5

SDS of cas: 37622-90-5, Ethyl 4-pyrazolecarboxylate, also known as Ethyl pyrazole-4-carboxylate, is a useful research compound. Its molecular formula is C6H8N2O2 and its molecular weight is 140.14 g/mol. The purity is usually 95%.

Yin, Yuan;Chen, Cheng-Juan;Yu, Ru-Nan;Shu, Lei;Zhang, Tian-Tai;Zhang, Da-Yong research published 《 Discovery of novel selective Janus kinase 2 (JAK2) inhibitors bearing a 1H-pyrazolo[3,4-d]pyrimidin-4-amino scaffold》, the research content is summarized as follows. Janus kinases (JAKs) regulate various cancers and immune responses and are targets for the treatment of cancers and immune diseases. A new series of 1H-pyrazolo[3,4-d]pyrimidin-4-amino derivatives were synthesized and optimized by introducing a functional 3,5-disubstituted-1H-pyrazole moiety into the C-3 moiety of pyrazole template, and then were biol. evaluated as potent Janus kinase 2 (JAK2) inhibitors. Among these mols., inhibitors 11f(I), 11g(II), 11h(III) and 11k(IV) displayed strong activity and selectivity against the JAK2 kinase, with IC₅₀ values of 7.2 nM, 6.5 nM, 8.0 nM and 9.7 nM, resp. In particular, the cellular inhibitory assay and western blot anal. further support the JAK2 selectivity of II also in cells. Furthermore, II also exhibited potent inhibitory activity in lymphocytes proliferation assay and delayed hypersensitivity assay. Taken together, the novel JAK2 selective inhibitors discovered in this study may be potential lead compounds for new drug discovery via further development of more potent and selective JAK2 inhibitors.

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

Yogo, Takatoshi team published research in Journal of Medicinal Chemistry in 2016 | 37622-90-5

Yogo, Takatoshi;Nagamiya, Hiroyuki;Seto, Masaki;Sasaki, Satoshi;Shih-Chung, Huang;Ohba, Yusuke;Tokunaga, Norihito;Lee, Gil Nam;Rhim, Chul Yun;Yoon, Cheol Hwan;Cho, Suk Young;Skene, Robert;Yamamoto, Syunsuke;Satou, Yousuke;Kuno, Masako;Miyazaki, Takahiro;Nakagawa, Hideyuki;Okabe, Atsutoshi;Marui, Shogo;Aso, Kazuyoshi;Yoshida, Masato research published 《 Structure-Based Design and Synthesis of 3-Amino-1,5-dihydro-4H-pyrazolopyridin-4-one Derivatives as Tyrosine Kinase 2 Inhibitors》, the research content is summarized as follows. We report herein the discovery and optimization of 3-amino-1,5-dihydro-4H-pyrazolopyridin-4-one TYK2 inhibitors. High-throughput screening against TYK2 and JAK1-3 provided aminoindazole derivative 1 (I) as a hit compound Scaffold hopping of the aminoindazole core led to the discovery of 3-amino-1,5-dihydro-4H-pyrazolopyridin-4-one derivative 3 (III) as a novel chemotype of TYK2 inhibitors. Interestingly, initial SAR study suggested that this scaffold could have a vertically flipped binding mode, which prompted us to introduce a substituent at the 7-position as a moiety directed toward the solvent-exposed region. Introduction of a 1-methyl-3-pyrazolyl moiety at the 7-position resulted in a dramatic increase in TYK2 inhibitory activity, and further optimization led to the discovery of 20 (XX). Compound 20 inhibited IL-23-induced IL-22 production in a rat PD assay, as well as inhibited IL-23 signaling in human PBMC. Furthermore, 20 showed selectivity for IL-23 signaling inhibition against GM-CSF, demonstrating the unique cytokine selectivity of the novel TYK2 inhibitor.

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