134653-70-6Relevant articles and documents
Simple access toward 3-halo- and 3-nitro-pyrazolo[1,5-a] pyrimidines through a one-pot sequence
Castillo, Juan-Carlos,Rosero, Hernán-Alejandro,Portilla, Jaime
, p. 28483 - 28488 (2017)
Herein, a regioselective, time-efficient and one-pot route for the synthesis of diversely substituted 3-halo- and 3-nitropyrazolo[1,5-a]pyrimidines in good to excellent yields through a microwave-assisted process is provided. The reaction features a sequential cyclocondensation reaction of β-enaminones with NH-5-aminopyrazoles, followed by a regioselective electrophilic substitution with easily available electrophilic reagents. This methodology is distinguished by its short reaction times, high-yield, operational simplicity, broad substrate scope and pot-economy. Furthermore, these 3-functionalized heterocycles have been successfully used in the synthesis of 3-alkynyl and 3-aminopyrazolo[1,5-a]pyrimidines in yields up to 92%.
Design, Synthesis, In Silico Docking Studies, and Antibacterial Activity of Some Thiadiazines and 1,2,4-Triazole-3-Thiones Bearing Pyrazole Moiety
Nayak, Soukhyarani Gopal,Poojary, Boja
, p. 97 - 106 (2020)
Abstract: In view of developing new bioactive compounds, a series of 6-(substituted-phenyl)-3-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and 4-[(substituted-benzylidene)amino]-5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones were synthesized in good yields. The compounds were confirmed by elemental analyses, mass spectrometry, FT-IR, 1H, and 13CNMR spectroscopy. To study the binding interactions of the derivatives with the receptor, they were docked with the prostaglandin D2 synthase (PGDS). The docking pose and non-covalent interactions gave insights into their plausible inhibitory action. They showed good antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Particularly, chloro, fluoro, dimethoxy, and dihydroxy substituted derivatives displayed good activity over other derivatives.
A facile, regioselective synthesis of pyrazolo[1, 5-a]pyrimidine analogs in the presence of KHSO4 in aqueous media assisted by ultrasound and their anti-inflammatory and anti-cancer activities
Kaping, Shunan,Kalita, Utpalparna,Sunn, Melboureen,Singha, Laishram Indira,Vishwakarma, Jai Narain
, p. 1257 - 1276 (2016)
Abstract: An environmentally benign, simple, efficient, and convenient route is described for the synthesis of novel pyrazolo[1,5-a]pyrimidine derivatives under ultrasound irradiation assisted by KHSO4 in aqueous medium. 3-(4-Methoxyphenyl)-3-o
Design, synthesis, and pharmacological studies of some new Mannich bases and S-alkylated analogs of pyrazole integrated 1,3,4-oxadiazole
Viveka, Shivapura,Dinesha,Shama, Prasanna,Nagaraja, Gundibasappa Karikannar,Deepa, Nagaraju,Sreenivasa, Marikunte Yanjarappa
, p. 2597 - 2617 (2016)
A facile and convenient synthesis of Mannich bases 5a-f and S-alkylated derivatives 6a-f and 7a-f has been carried out from the key intermediate 5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole-2(3H)-thione (4). Intermediate 4 was obtained from one-pot reaction of ethyl acetoacetate, phenylhydrazine, and N,N-dimethylformamide dimethyl acetal (DMF-DMA) followed by reaction with hydrazine hydrate and carbon disulfide. The structure of the newly synthesized compounds was established on the basis of elemental analysis, infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopic data. All synthesized compounds were screened for in vivo antiinflammatory, in vivo analgesic, and in vitro antimicrobial activity. From the activity studies, it was concluded that, among all the derivatives, compounds 5c, 5e, 5f, 6c, 7b, and 7c showed potent antiinflammatory activity, whereas 5b, 5c, 5e, 5f, 6c, 6f, 7b, 7c, and 7e exhibited good analgesic activity. Compounds 6a, 6c, 7b, 7c, and 7d showed maximum activity against the bacterial strains. Efforts were also made to establish structure-activity relationships among the tested compounds.
Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation
Vekariya, Mayur K.,Vekariya, Rajesh H.,Brahmkshatriya, Pathik S.,Shah, Nisha K.
, p. 1683 - 1691 (2018)
A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50??20?nm); which can be further optimized to have selectivity over other kinase isoforms.
Novel N-thioamide analogues of pyrazolylpyrimidine based piperazine: Design, synthesis, characterization, in-silico molecular docking study and biological evaluation
Vekariya, Mayur K.,Patel, Dhaval B.,Pandya, Pranav A.,Vekariya, Rajesh H.,Shah, Prapti U.,Rajani, Dhanji P.,Shah, Nisha K.
, p. 551 - 565 (2019)
Utilizing molecular hybridization approach, a progression of novel pyrazolylpyrimidine based N-thioamide derivatives of piperazine were identified in an effort to develop newer antibacterial and antitubercular agents against the cumulative bacterial resistance. Spectral analysis using Mass, 1H NMR and 13C NMR spectral techniques have been studied in order to affirm the structure of synthesized end molecules. Biological evaluation of all synthesized molecules were studied in-vitro for their antibacterial, antituberculosis and antimalarial efficacy against various bacterial and fungal strains, H37Rv and Plasmodium falciparum respectively. Molecular docking and ADME properties prediction study were also carried out for better insights of responsible proteins with the synthesized molecules. Interestingly, some of the pyrazolylpyrimidine based piperazine N-thioamide derivatives exhibited potential antibacterial, antifungal and antimalarial potency.
A facile synthesis of 2,2-disubstituted 5-carbethoxy-2,3-dyhydro-4H-pyran-4-ones
Totah, Nancy I.,Chen, Deqi
, p. 213 - 216 (1998)
A facile synthesis of 5-carbethoxy-2,3-dihydropyran-4-ones is described via the condensation of ethyl 2-formyl-3-oxobutanoate with various ketones.
Synthesis method of 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid
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Paragraph 0025; 0032; 0037, (2021/03/13)
The invention relates to a synthesis method of 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid, and the method comprises the following steps: 1, carrying out condensation reaction on N, N-dimethylamino ethyl acrylate, triethylamine and acetyl chloride to generate ethyl 2-dimethylamino-3-oxobutyrate and triethylamine hydrochloride; 2, carrying out a cyclization reaction on 2-dimethylamino ethyl-3-oxobutyrate and methylhydrazine to generate 1, 3-dimethyl-1H-pyrazole ethyl-4-formate and a dimethylamine aqueous solution; 3, carrying out a reaction on formic acid, ethyl acetoacetate and dimethylamine generated in the step 2 cyclization reaction to generate 2-dimethylamino ethyl-3-oxobutyrate and water, wherein the ethyl 2-dimethylamino-3-oxobutyrate generated in the step 3 is recycled as a reactantin the step 2; 4, hydrolyzing the ethyl 1, 3-dimethyl-1H-pyrazole-4-formate to obtain the 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid. The 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid has the advantages of few synthesis steps, safe reaction process and no three-waste pollution, and is suitable for industrial batch large-scale preparation.
INDAZOLES AND AZAINDAZOLES AS LRRK2 INHIBITORS
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Page/Page column 347, (2021/01/29)
The present invention is directed to indazole and azaindazole compounds which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.
Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
, p. 4623 - 4661 (2021/05/07)
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
