- Anti-inflammatory Exploration of Sulfonamide Containing Diaryl Pyrazoles with Promising COX-2 Selectivity and Enhanced Gastric Safety Profile
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Novel sulfonamide containing diaryl pyrazoles were synthesized and were subsequently tested for their in vitro cyclooxygenase inhibitory assay. Compounds that showed promising in vitro COX-2 IC50 values and selectivity indices were then evaluat
- Pavase, Laxmikant S.,Mane, Dhananjay V.,Baheti, Kamalkishor G.
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Read Online
- Design, synthesis and biological evaluation of some novel N-arylpyrazole derivatives bearing the sulfonamide moiety as cytotoxic agents
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A series of novel N-arylpyrazole derivatives (4a–4l) bearing the sulfonamide moiety were synthesized by the condensation reaction of 1,3-dicarbonyl compounds with 4-hydrazinylbenzenesulfonamide. The structures of the obtained compounds were established on
- Duan, Xiaobo,Wang, Yingxing,Feng, Weipei,Yang, Yaxing,Li, Hongyan,Li, Shenghui,Yang, Xiaobing,Zhang, Jinchao,Wang, Shuxiang,Zhou, Guoqiang,Zhou, Chuanqi
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Read Online
- Synthetic method of celecoxib intermediate P-hydrazinamide hydrochloride
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The method, comprises the following steps :1): preparing a sulfanilamide hydrochloric acid aqueous solution, to prepare a sodium nitrite solution ;2) to acidify, and then acidifying the resulting reaction solution to 1 with ;3) powder, activated carbon to
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Paragraph 0037-0044
(2020/03/17)
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- HFO-1234yf as a CF3-Building Block: Synthesis and Chemistry of CF3-Ynones
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Reaction of low cost, readily available 4th generation refrigerant gas 2,3,3,3-tetrafluoropropene (HFO-1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3-trifluoropropynide, addition of which to a range of aldehydes formed CF3-alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess–Martin periodinane (DMP) to give substituted CF3-ynones with minimal purification required. Michael-type additions of alcohol and amine nucleophiles to CF3-ynones are rapid and selective, affording a range of CF3-enone ethers and enaminones in excellent yields with high stereoselectivity for the Z-isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF3-substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti-arthritis drug celecoxib from HFO-1234yf in just three steps.
- Murray, Ben J.,Marsh, Thomas G. F.,Yufit, Dmitri S.,Fox, Mark A.,Harsanyi, Antal,Boulton, Lee T.,Sandford, Graham
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supporting information
p. 6236 - 6244
(2020/09/15)
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- Pyrazole–coumarin and pyrazole–quinoline chalcones as potential antitubercular agents
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Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole–coumarin chalcones and pyrazole–quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well c
- Kumar, Gautam,Siva Krishna, Vagolu,Sriram, Dharmarajan,Jachak, Sanjay M.
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- CONTINUOUS PROCESSES FOR THE MANUFACTURE OF CELOCOXIB
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A continuous process for the manufacture of celecoxib includes reacting a stream of a first solution of 4'-methylacetophenone in a first organic solvent and a stream of a second solution of ethyl trifluoroacetate in a second organic solvent in a first reactor in the presence of a base at a first reaction temperature of between 45°C and 90°C and at a first reaction pressure to form 4,4,4-Trifluoro-1-(4-methylphenyl)butane-1,3-dione. The first reaction pressure prevents boiling inside the first reactor. A stream of a first reactor product from the first reactor is continuously withdrawn, the first reactor product including a solution of 4,4,4-Trifluoro-1-(4-methylphenyl)butane-1,3-dione in the first organic solvent and the second organic solvent. A stream of the first reactor product and a stream of a third solution of (4-Sulfamoylphenyl)hydrazine hydrochloride in a third organic solvent are reacted in a second reactor at a second reaction temperature of between 80°C and 110°C and at a second reaction ressure to form celecoxib. The second reaction pressure prevents boiling inside the second reactor. A stream of a second reactor product is continuously withdrawn from the second reactor, the second reactor product including a solution of celecoxib in organic solvent.
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Page/Page column 14
(2019/04/26)
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- An Integrated Continuous Flow Micro-Total Ultrafast Process System (μ-TUFPS) for the Synthesis of Celecoxib and Other Cyclooxygenase Inhibitors
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Integrated continuous manufacturing has emerged as a promising device for the rapid manufacturing of active pharmaceutical ingredients (APIs). We herein report a newly designed continuous flow micro-total process system platform for the rapid manufacturing of celecoxib, a selective nonsteroidal anti-inflammatory drug. This approach has been proven generally for the synthesis of several alkyl and aryl substituted pyrazoles. In order to minimize the tedious work-up process of potential reaction intermediates/products, we have developed a continuous flow extraction and separation platform to carry out the entire reaction sequence resulting in a short residence time with good yield. The present process was further extended to gram-scale synthesis of the COX-2-related API, viz. celecoxib, in the continuous flow process.
- Sthalam, Vinay Kumar,Singh, Ajay K.,Pabbaraja, Srihari
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supporting information
p. 1892 - 1899
(2019/10/11)
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- Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors
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Abstract Inhibition of cyclooxygenase-2 (COX-2) is a promising anti-inflammatory therapeutic strategy, but long-term medication with COX-2-inhibitors (coxibs) may be associated with adverse cardiovascular effects. Functionalization of existing lead struct
- Bechmann, Nicole,Kniess, Torsten,K?ckerling, Martin,Pigorsch, Arne,Steinbach, J?rg,Pietzsch, Jens
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p. 3295 - 3300
(2015/07/08)
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- Synthesis of tri- and tetrasubstituted pyrazoles via Ru(II) catalysis: Intramolecular aerobic oxidative C-N coupling
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An unprecedented ruthenium(II)-catalyzed intramolecular oxidative C-N coupling method has been developed for the facile synthesis of a variety of synthetically challenging tri- and tetrasubstituted pyrazoles. Dioxygen gas is employed as the oxidant in this transformation. The reaction demonstrates excellent reactivity, functional group tolerance, and high yields.
- Hu, Jiantao,Chen, Shi,Sun, Yonghui,Yang, Jing,Rao, Yu
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supporting information
p. 5030 - 5033,4
(2012/12/12)
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- Efficient sequential synthesis of PET Probes of the COX-2 inhibitor [ 11C]celecoxib and its major metabolite [11C]SC-62807 and in vivo PET evaluation
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Synthesis of [11C]celecoxib, a selective COX-2 inhibitor, and [11C]SC-62807, a major metabolite of celecoxib, were achieved and the potential of these PET probes for assessing the function of drug transporter in biliary excretion was
- Takashima-Hirano, Misato,Takashima, Tadayuki,Katayama, Yumiko,Wada, Yasuhiro,Sugiyama, Yuichi,Watanabe, Yasuyoshi,Doi, Hisashi,Suzuki, Masaaki
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supporting information; experimental part
p. 2997 - 3004
(2011/06/22)
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- CYP2C9 structure-metabolism relationships: Optimizing the metabolic stability of COX-2 inhibitors
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The cytochrome P450 (CYP) family is composed of a large group of monooxygenases that mediate the metabolism of xenobiotics and endogenous compounds. CYP2C9, one of the major isoforms of the CYP family, is responsible for the phase I metabolism of a variety of drugs. The aim of the present investigation is to use rational design together with MetaSite, a metabolism site prediction program, to synthesize compounds that retain their pharmacological effects but that are metabolically more stable in the presence of CYP2C9. The model compound for the study is the nonsteroidal anti-inflammatory drug celecoxib, a COX-2 selective inhibitor and known CYP2C9 substrate. Thirteen analogs of celecoxib were designed, synthesized, and evaluated with regard to their metabolic properties and pharmacologic effects. The docking solutions and the predictions from MetaSite gave useful information leading to the design of new compounds with improved metabolic properties.
- Ahlstr?m, Marie M.,Ridderstr?m, Marianne,Zamora, Ismael,Luthman, Kristina
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p. 4444 - 4452
(2008/02/13)
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- Methods and compositions for diagnostic and therapeutic targeting of COX-2
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The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.
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(2008/06/13)
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- Compounds and methods for inducing apoptosis in proliferating cells
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Compounds useful for inducing apoptosis in proliferative cells, particularly cancer cells, including but not limited to prostate cancer, leukemia, non-smalll cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, bladder cancer, lymphoma, and breast cancer. These compounds are particularly useful in the treatment of androgen-independent cancers, including hormone-refractory prostate cancer. Further provided are methods of treating cancer in a subject in need of such treatment using the compounds of the present invention. Further provided are methods for using the compounds of the present invention to treat, inhibit, or delay the onset of cancer in a subject. Further provided are methods of inducing apoptosis in rapidly proliferating cells, particularly, though not necessarily cancer cells, using the compounds of the present invention.
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- Processes for the preparation of 1,5-diaryl-3-substituted-pyrazoles
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Provided are processes and chemical intermediates useful for preparing a compound of the formula I wherein X is selected from the group consisting of C1-C6 trihalomethyl; C1-C6 alkyl; and an optionally substituted or di-substituted phenyl group of formula II: Y and Z are independently selected from the group consisting of substituted and unsubstiotuted aryl
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- PROCESSES FOR THE PREPARATION OF 1,5-DIARYLPYRAZOLES
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Provided are processes for the preparation of the compound of the formula wherein R1, R3 and R4 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, nitro, lower alkyl, lower alkoxy, carboxy, C1-C6 trihaloalkyl, and cyano, and R is amino or lower alkyl Also provided are synthetic intermediates that are useful as intermediates in the preparation of the compound of the formula 1.
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