89193-16-8Relevant academic research and scientific papers
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 (2020/04/15)
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.
Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation
Yang, Wei,Li, Yingjun,Ai, Yong,Obianom, Obinna N.,Guo, Dong,Yang, Hong,Sakamuru, Srilatha,Xia, Menghang,Shu, Yan,Xue, Fengtian
, p. 11151 - 11164 (2019/12/27)
Dysregulation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of β-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.
Toward Continuous-Flow Synthesis of Biologically Interesting Pyrazole Derivatives
Das, Amrita,Ishitani, Haruro,Kobayashi, Shū
supporting information, p. 5127 - 5132 (2019/11/13)
A two-step continuous-flow synthesis of substituted pyrazole derivatives has been developed via the formation of vinylidene keto esters as key intermediates. Heterogeneous Ni2+-montmorillonite was found to be an efficient catalyst for orthoester condensation of 1,3-dicarbonyls under flow conditions. The intermediate reacted with methylhydrazine to afford pyrazole derivatives, for which suitable selection of a solvent played a key role in achieving high yields and excellent regioselectivities of the desired products. An application of this protocol has been demonstrated by the synthesis of a key intermediate for biologically active pyrazoles such as Bixafen. (Figure presented.).
Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity
De Vita, Elena,Schüler, Peter,Lovell, Scott,Lohbeck, Jasmin,Kullmann, Sven,Rabinovich, Eitan,Sananes, Amiram,He?ling, Bernd,Hamon, Veronique,Papo, Niv,Hess, Jochen,Tate, Edward W.,Gunkel, Nikolas,Miller, Aubry K.
supporting information, p. 8859 - 8874 (2018/10/09)
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.
Synthesis, biological evaluation and docking studies of a new series of tris-heterocycles containing pyrazole, triazole and oxadiazole
Kumar, Gaddam Rajesh,Shankar, Kurre,Reddy, Cherkupally Sanjeeva
, p. 687 - 699 (2019/05/22)
A new series of 3-aryl/hetaryl-6-(5-methyl-l-phenyl-lH-pyrazol-4-yl)-[l,2,4]triazolo[3,4-b][l,3,4]oxadiazoles 7a-j have been synthesized, characterized by spectral means, and evaluated for their antimicrobial and antioxidant properties. Amongst the screened compounds 7a-j, the triazole moiety bearing electron-withdrawing group on the 4th position of phenyl viz. 4-chlorophenyl 7c, 4-nitrophenyl 7f and 2,4-difluorophenyl 7h exhibit excellent antibacterial activity towards all the tested bacteria viz. Staphylococcus aureus. Bacillus licheniformis, Pseudomonas aeruginosa and Escherichia coli. On the other hand, triazole moiety bearing electron-donating group on the 4th position of phenyl viz. 4-hydroxyphenyl 7d, 4-methoxy-phenyl 7e and 4-aminophenyl 7g show prominent antifungal activity towards the tested fungi viz. Candida albicans and Fusarium oxysporum. These results are supported by molecular docking studies and through binding interactions as well. Antioxidant studies reveal that the compounds in which the triazole moiety bearing phenyl 7a, 4-methoxyphenyl 7e, 2,4-difluorophenyl 7h and 3-pyridyl 7j is present on the 4th position, display significant antioxidant "' properties. In brief, most of the newly synthesized compounds have emerged as potential antimicrobial and antioxidant agents for further development.
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 (2016/03/16)
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.
Synthesis and antibacterial activity of di-heteryl substitued [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazoles
Sanjeeva Reddy,Vani Devi,Sunitha,Kalyani,Nagaraj
, p. 590 - 597 (2017/01/18)
A new series of 3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-6-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)[1,2,4]triazolo [3,4-b][1,3,4]thiadiazoles 12a-j have been prepared and assayed for their antibacterial activity against human pathogenic Gram-positive bacteria viz., Staphylococcus aureus, Bacillus subtilis and Gram-negative Escherichia coli. Among the screened compounds 12b, 12c and 12f, in which phenyl ring of triazole moiety bear 4-chloro, 4-nitro and 4-fluoro substituents respectively, showed high activity against all the micro-organisms employed. The activities of these compounds are almost equal to the standards.
PROCESS FOR THE REGIOSELECTIVE SYNTHESIS OF PYRAZOLES
-
Page/Page column 24; 25, (2015/07/15)
A process is described for the synthesis of pyrazoles having general formula (I) which comprises the steps of mixing a compound having general formula (II) and a 1,2-disubstituted hydrazine having general formula (III) to form a reaction intermediate having general formula (IV) and the reaction mixture obtained in step i), in an acid environment, cyclizes to form a pyrazole having general formula (I), according to reaction scheme 1 Scheme 1.
Synthesis and antibacterial activity of N-substituted-[1,2,4]triazoles and 1,2,4-Triazole[3,4-b][1,3,4]thiadiazines
Sanjeeva Reddy,Sanjeeva Rao,Sunitha,Nagaraj
, p. 1283 - 1289 (2015/11/25)
New series of N-[3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-5- sulfanyl-4H-1,2,4-Triazol-4-yl]-N'-Arylthiourea derivatives 8a-e and 3-(5-methyl-1-phenyl-1H-4-pyrazolyl)-6-Aryl-7H-[1,2,4] triazolo[3,4- b][1,3,4]thiadiazines 9a-e have been prepared and screened for their antibacterial activity against four human pathogenic bacteria, Escherichia coli, Klebseilla pneumoniae, Shigella dysentriae and Shigella flexnei. Among the screened, compounds 8b, 8c and 8e, in which phenyl ring of isothiocyanate moiety bear 3-fluoro, 4-fluoro and 4-bromo substituents respectively, show high activity against all the micro-organisms employed. The compound 9c is highly active against all the test organisms employed. The zone of inhibition is more than what is found for the standard drug neomycin, and almost equal to the standard drug streptomycin.
nBu3P-catalyzed desulfonylative [3 + 2] cycloadditions of allylic carbonates with arylazosulfones to pyrazole derivatives
Zhang, Qi,Meng, Ling-Guo,Wang, Kuai,Wang, Lei
supporting information, p. 872 - 875 (2015/04/21)
Highly efficient nBu3P-catalyzed desulfonylative [3 + 2] cycloadditions of allylic carbonates with arylazosulfones were developed for the synthesis of pyrazole derivatives. The reactions proceed smoothly under mild conditions to gene
