- Discovery of pyrazole N-aryl sulfonate: A novel and highly potent cyclooxygenase-2 (COX-2) selective inhibitors
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Based on a new pyrazole sulfonate synthetic method, a novel class of molecules with a basic structure of pyrazole N-aryl sulfonate have been designed and synthesized. The interest in conducting intensive research stems from quite evident anti-inflammatory effects exhibited by the compounds in preliminary animal experiments. A series of compounds were synthesized by different substitutions of the R1, R2, and R3 groups. Within the series, 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and phenyl 5-methyl-3-(4-(trifluoromethyl) phenyl)-1H-pyrazole-1-sulfonate exhibited excellent anti-inflammatory activity (% inhibition of auricular edemas = 27.0 and 35.9, respectively); the in vivo analgesic activity of phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate was confirmed to be effective (inhibition ratio of writhing = 50.7% and 48.5% separately), and compounds phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate, 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate were identified as selective COX-2 inhibitors (SI = 455, 10,497 and >189 severally). In Acute Oral Toxicity assays conducted in vivo, the lethal dose 50 (LD50) of 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate to mice was >2000 mg/kg BW.
- Yao, Haiyan,Guo, Quanping,Wang, Mengran,Wang, Rui,Xu, Zhaoqing
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- Pyrazole compound containing N-aryl sulfonate and synthesis and application thereof
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The invention discloses a pyrazole compound containing N-aryl sulfonate. A structural formula of the pyrazole compound is shown in the description. Proofed by pharmacological study, the pyrazole compound has the advantages that the activity of cyclooxygenase 2 is inhibited; the high-efficiency inhibition function on the generation of cyclooxygenase 2 due to inflammation mediums is realized, so that the pyrazole compound can be used as an active matter, and the prepared anti-inflammation medicine can be used for treating the inflammations, such as rheumatic arthritis and rheumatalgia, and the diseases and symptoms, such as fevers.
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Paragraph 0029
(2018/07/10)
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- Direct synthesis of 1,3-dicarbonyl compounds via radical coupling of aldehydes with ketones under metal-free conditions
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An efficient approach for the synthesis of 1,3-diketones from aldehydes and ketones has been developed using Bu4NI (TBAI) as the catalyst. In the presence of DTBP-TBHP/p-TsOH, aldehydes undergo radical coupling with ketones to provide the desired products in moderate to high yields at 120 °C. Although various substituents on the aromatic ring of aldehydes are well tolerable under the standard reaction conditions, the protocol is limited by the scope of ketones. The method exhibits advantages in terms of the easy access of the starting materials, operational simplicity, functional group tolerance, and the absence of metal catalyst.
- Shen, Xuqian,Borah, Arun Jyoti,Cao, Xihan,Pan, Weixiang,Yan, Guobing,Wu, Xiangmei
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supporting information
p. 6484 - 6487
(2015/11/16)
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- 2-(1H-Pyrazol-1-yl)acetic acids as chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes (CRTh2) antagonists
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In this manuscript, the synthesis and biological activity of a series of pyrazole acetic acid derivatives as CRTh2 antagonists is presented. Biological evaluation in vitro revealed that the pyrazole core showed in several cases a different structure-activity relationship (SAR) to that of related indole acetic acid. A potent series of ortho-sulfonyl benzyl substituents was found, from which compounds 27 and 63 were advanced to in vivo profiling.
- Andrés, Miriam,Bravo, Mónica,Buil, Maria Antonia,Calbet, Marta,Castillo, Marcos,Castro, Jordi,Eichhorn, Peter,Ferrer, Manel,Lehner, Martin D.,Moreno, Imma,Roberts, Richard S.,Sevilla, Sara
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p. 168 - 184
(2014/01/06)
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- Direct route to 1,3-diketones by palladium-catalyzed carbonylative coupling of aryl halides with acetylacetone
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Man up your magnesium! By employing a MgCl2/Et3N system, aryl diketones can be generated from the Pd-catalyzed carbonylative α-arylation of acetylacetone with aryl bromides (see scheme). The method is ideal for the introduction of carbon isotopes into more complex structures, since only stoichiometric amounts of carbon monoxide are employed. Copyright
- Korsager, Signe,Nielsen, Dennis U.,Taaning, Rolf H.,Lindhardt, Anders T.,Skrydstrup, Troels
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p. 17687 - 17691
(2014/01/17)
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- PYRAN-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
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The invention relates to pyran spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the composition
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Paragraph 00192; 00195; 00197
(2013/07/31)
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- HETEROCYCLES USEFUL AS INHIBITORS OF CARBONIC ANHYDRASE
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Sulfonamides and pharmaceutical compositions containing the compounds useful in controlling intraocular pressure are disclosed. Methods for controlling intraocular pressure through administration of the compositions are also disclosed.
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Page/Page column 92
(2008/06/13)
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- Novel cAMP PDE III Inhibitors: 1,6-Naphthyridin-2(1H)-ones
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Two series of medorinone (3) analogs were prepared by modifications at C(2) and C(5).The C(2)-series was prepared from 2-chloro-5-methyl-1,6-naphthyridine (4) by replacement of the chloro group with various nucleophiles.The C(5)-series was prepared from 5
- Singh, Baldev,Lesher, George Y.,Pluncket, Kevin C.,Pagani, Edward D.,Bode, Donald C.,et al.
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p. 4858 - 4865
(2007/10/02)
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