- Electrochemical oxygenation of sulfides with molecular oxygen or water: Switchable preparation of sulfoxides and sulfones
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A practical and eco-friendly method for the controllable aerobic oxygenation of sulfides by electrochemical catalysis was developed. The switchable preparation of sulfoxides and sulfones was effectively controlled by reaction time, in which both molecular oxygen and water can be used as the oxygen source under catalyst and external oxidant-free conditions. The electrochemical protocol features a broad substrate scope and excellent site selectivity and is successfully applied to the modification of some sulfide-containing pharmaceuticals and their derivatives. This journal is
- Li, Jin-Heng,Li, Yang,Sun, Qing,Xue, Qi,Zhang, Ting-Ting
-
supporting information
p. 10314 - 10318
(2021/12/17)
-
- Palladium-Catalyzed Cross-Coupling of Alkenyl Carboxylates
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Carboxylate esters have many desirable features as electrophiles for catalytic cross-coupling: they are easy to access, robust during multistep synthesis, and mass-efficient in coupling reactions. Alkenyl carboxylates, a class of readily prepared non-aromatic electrophiles, remain difficult to functionalize through cross-coupling. We demonstrate that Pd catalysis is effective for coupling electron-deficient alkenyl carboxylates with arylboronic acids in the absence of base or oxidants. Furthermore, these reactions can proceed by two distinct mechanisms for C?O bond activation. A Pd0/II catalytic cycle is viable when using a Pd0 precatalyst, with turnover-limiting C?O oxidative addition; however, an alternative pathway that involves alkene carbopalladation and β-carboxyl elimination is proposed for PdII precatalysts. This work provides a clear path toward engaging myriad oxygen-based electrophiles in Pd-catalyzed cross-coupling.
- Becica, Joseph,Heath, Oliver R. J.,Leitch, David C.,Zheng, Cameron H. M.
-
supporting information
p. 17277 - 17281
(2020/07/31)
-
- Multicomponent Reductive Cross-Coupling of an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Diversely Functionalized Sulfones
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Conventionally, sulfones are prepared by oxidation of sulfides with strong oxidants. Now, a multicomponent reductive cross-coupling involving an inorganic salt (sodium metabisulfite) for the straightforward construction of sulfones is disclosed. Both intramolecular and intermolecular reductive cross-couplings were comprehensively explored, and diverse sulfones were accessible from the corresponding alkyl and aryl halides. Intramolecular cyclic sulfones were systematically obtained from five- to twelve-membered rings. Naturally occurring aliphatic systems, such as steroids, saccharides, and amino acids, were highly compatible with the SO2-insertion reductive cross-coupling. Four clinically applied drug molecules, which include multiple heteroatoms and functional groups with active hydrogens, were successfully prepared via a late-stage SO2 insertion. Mechanistic studies show that alkyl radicals and sulfonyl radicals were both involved as intermediates in this transformation.
- Meng, Yingying,Wang, Ming,Jiang, Xuefeng
-
supporting information
p. 1346 - 1353
(2019/12/11)
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- PURIFIED FORMS OF ROFECOXIB, METHODS OF MANUFACTURE AND USE
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The subject matter disclosed herein relates to rofecoxib, also known as TRM-201 or RXB-201, its method of manufacture, and use. In certain aspects, the highly pure or substantially pure rofecoxib as provided herein has a favorable purity profile and is the active ingredient in a pharmaceutical composition that is administered to treat or prevent a number of conditions, including pain associated with a condition caused by a bleeding disorder.
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- Selective oxidation of (hetero)sulfides with molecular oxygen under clean conditions
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The development of eco-friendly and switchable catalytic systems for the conversion of a sole raw-material into distinct high-value products is a particularly attractive concept and a daunting synthetic challenge. In the present work, the first example of efficient and selective oxidation of sulfides to sulfones and sulfoxides using molecular oxygen under clean conditions was established.
- Liu, Kai-Jian,Deng, Ji-Hui,Yang, Jie,Gong, Shao-Feng,Lin, Ying-Wu,He, Jun-Yi,Cao, Zhong,He, Wei-Min
-
supporting information
p. 433 - 438
(2020/02/13)
-
- Oxidation of aromatic sulfides with molecular oxygen: Controllable synthesis of sulfoxides or sulfones
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The recent development of selective oxidation of aromatic sulfides with molecular oxygen was highlighted. The sulfoxides and sulfones could be obtained by simply switching the reaction media, i.e., bis(2-butoxyethyl)ether (BBE) or poly(ethylene glycol)dimethyl ether (PEGDME). The application of the high-boiling-point polyether as an initiator and green media can eliminate the need of large quantities of additives and volatile solvents. This strategy represents an economic and eco-friendly method that could find potential applications.
- Tang, Lili,Du, Kejie,Yu, Bing,He, Liangnian
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p. 2991 - 2992
(2020/03/24)
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- Aryl alkyl sulfone compound and reducing coupling method for constructing sulfone compounds
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The invention discloses an aryl alkyl sulfone compound shown as a formula (1) and a synthetic method thereof. The aryl alkyl sulfone compound is prepared by taking an aromatic iodide, an inorganic sulfur reagent and an alkyl bromide as reaction raw materials to carry out reacting in a solvent under action of alkali, a catalyst, a ligand, a reducing agent and an additive. According to the invention, an inorganic sulfur reagent is used as a sulfur source to construct the aryl alkyl sulfone compound in one step under catalysis and reduction conditions, so that the defect in synthesizing the arylalkyl sulfone compound by conventional oxidation of thioether is avoided. The aryl alkyl sulfone compound developed by the invention can be used for synthesizing aryl alkyl sulfone medicines.
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-
Paragraph 0377-0381
(2019/12/25)
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- Selective Late-Stage Oxygenation of Sulfides with Ground-State Oxygen by Uranyl Photocatalysis
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Oxygenation is a fundamental transformation in synthesis. Herein, we describe the selective late-stage oxygenation of sulfur-containing complex molecules with ground-state oxygen under ambient conditions. The high oxidation potential of the active uranyl cation (UO22+) enabled the efficient synthesis of sulfones. The ligand-to-metal charge transfer process (LMCT) from O 2p to U 5f within the O=U=O group, which generates a UV center and an oxygen radical, is assumed to be affected by the solvent and additives, and can be tuned to promote selective sulfoxidation. This tunable strategy enabled the batch synthesis of 32 pharmaceuticals and analogues by late-stage oxygenation in an atom- and step-efficient manner.
- Li, Yiming,Rizvi, S. Aal-e-Ali,Hu, Deqing,Sun, Danwen,Gao, Anhui,Zhou, Yubo,Li, Jia,Jiang, Xuefeng
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p. 13499 - 13506
(2019/08/21)
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- Sulfoxide and sulfone compounds, as well as selective synthesis method and application thereof
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The invention discloses a method for selectively synthesizing a sulfoxide compound shown as a formula (II) and a sulfone compound shown as a formula (III). In a reaction solvent, thioether (I) is usedas a reaction raw material and oxygen as an oxidation reagent, under the catalytic action of visible light and a photosensitive reagent; under the assistance of an additive, when a large-polarity proton-containing additive such as an acid and an alcohol or a solvent or an additive with excellent electron donating ability is used, a sulfoxide compound (II) is selectively generated; and when a small-polarity aprotic additive or a solvent is used, a sulfone compound (III) is selectively generated. The synthesis method has the advantages of easily available and cheap raw materials, simple reaction operation, mild reaction conditions, high yield and excellent functional group tolerance. According to the invention, synthesis and modification of some medicines are realized, and an efficient method for selectively constructing sulfoxide and sulfone compounds is provided for medicinal chemistry research.
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Paragraph 0049-0052; 0174-0177
(2019/12/02)
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- Stereoselective synthesis and anti-proliferative effects on prostate cancer evaluation of 5-substituted-3,4-diphenylfuran-2-ones
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Series of 5-substituted-3,4-diphenylfuran-2-ones were stereoselectively prepared. Their potential anti-proliferative effects on prostate cancer and some of their cyclooxygenases (COXs) inhibitory activities were evaluated. Structure-activity relationship (SAR) data, acquired by substituent modification at the para-position and ortho-position of the C-3 phenyl ring and 5-substituted modification of the central furanone, showed that 3-(2-chloro-phenyl)-4-(4-methanesulfonyl-phenyl)-5-(1-methoxy-ethyl) -5H-furan-2-one (13p) was the most potent compound and could effectively reduce the proliferation of prostate cancer cells (PC3 cell IC50 = 20 μM; PC3 PCDNA cell IC50 = 5 μM; PC3 SKP2 cell IC50 = 5 μM; DU145 cell IC50 = 25 μM). The cell cycle analysis for 13p in DU145 indicated that 13p may induce G1 phase arrest.
- Liu, Gai-Zhi,Xu, Hai-Wei,Wang, Peng,Lin, Zong-Tao,Duan, Ying-Chao,Zheng, Jia-Xin,Liu, Hong-Min
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p. 323 - 336
(2013/10/01)
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- One-pot synthesis of 3,4-diaryl-substituted 2(5 H)-furanone and its commercial application
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One-pot synthesis of 3,4-diaryl substituted 2(5H)-furanones was established and its commercial application has been demonstrated by accomplishing total synthesis of rofecoxib, under mild reaction conditions, with good yields and purity.
- Argade, Anil,Desai, Jigar,Thombare, Pravin,Shah, Kiran,Gite, Sanjay,Prajapati, Vijay,Pandey, Bipin,Jain, Mukul,Patel, Pankaj,Bahekar, Rajesh
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p. 3140 - 3149
(2012/11/07)
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- CO-CRYSTALS OF TRAMADOL AND COXIBS
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The present invention relates to co-crystals of tramadol and co-crystal formers selected from NSAIDs/coxibs, processes for preparation of the same and their uses in pharmaceutical formulations for the treatment of pain.
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- Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin D derivatives and a cyclooxgenase-2 inhibitor
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The present invention relates to pharmaceutical compositions and methods of treatment comprising administering to a patient in need thereof a combination of a 2-alkylidene-19-nor-vitamin D derivative and a cyclooxgenase-2 inhibitor, or a pharmaceutically acceptable salt or prodrug thereof. Particularly, the present invention relates to pharmaceutical compositions and methods of treatment comprising administering to a patient in need thereof 2-methylene-19-nor-20(S)-10,25-dihydroxyvitamin D3 and a cyclooxgenase-2 inhibitor, or a pharmaceutically acceptable salt or prodrug thereof.
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Page/Page column 6
(2010/02/11)
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- Preparation of aryl-substituted butenolides using mucohalic acids
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Methods and materials for preparing 3-aryl-2-buten-4-olides and 2,3-bisaryl-2-buten-4-olides are disclosed. The methods include reacting a mucohalic acid with a reducing agent to give a 2,3-dihalo-2-buten-4-olide, which undergoes at least one Pd catalyzed cross-coupling reaction with an arylboronic acid.
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Page/Page column 9
(2008/06/13)
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- PROCESS FOR THE MANUFACTURE OF ROFECOXIB
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The present invention provides a simplified and commercial scale process for the manufacture of Rofecoxib. The invention comprises of oxidizing 4-(4-methylthiophenyl)-3-phenyl-2(5H)-furanone using hydrogen peroxide as oxidant, acetic acid as solvent and sodium tungstate as catalyst under suitable reaction conditions to get rofecoxib.
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Page/Page column 4-5
(2008/06/13)
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- METHOD FOR PREPARING PHENYL HETEROCYCLES AS CYCLOOXYGENASE-2 INHIBITOR
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The present invention relates to a method for preparing phenyl heterocycle as cyclooxygenase-2 inhibitor useful in the treatment of other cyclooxygenase meditated diseases, which is environmentally harmonious and has an improved productivity. More particularly, it relates to a method for preparing phenyl heterocycle as cyclooxygenase-2 inhibitor, characterized in providing a high-purity compound of Formula 5 with the low cost of production and a simple process, which is harmless to human and environmental pollution due to not generating a halogen gas when preparing, and comprising the steps of lactonization reaction with a compound of Formula 1 as an initiator; substitution reaction; and oxidation reaction.
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Page/Page column 6; 11
(2008/06/13)
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- Sulfonamido, azidosulfonyl and N-acetylsulfonamido analogues of rofecoxib: 4-[4-(N-acetylsulfonamido)phenyl]-3-(4-methanesulfonylphenyl)-2(5H)furanone is a potent and selective cyclooxygenase-2 inhibitor
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4-[4-(N-Acetylsulfonamido)phenyl]-3-(4-methanesulfonylphenyl)-2(5H) furanone, possessing a N-acetylsulfonamido pharmacophore, has been identified as a potent and selective COX-2 inhibitor that has the potential to acetylate the COX-2 isozyme.
- Zarghi, Afshin,Rao, P.N. Praveen,Knaus, Edward E.
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p. 1957 - 1960
(2007/10/03)
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- PROCESS OF PREPARING PHENYL HETEROCYCLES USEFUL AS COX-2 INHIBITORS
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The invention encompasses a process for making compounds of Formula I useful in the treatment of inflammation and other cyclooxygenase-2 mediated diseases. I
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- Agents and methods for treatment of cancer
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Agents and methods for chemoprevention and treatment of neoplasia are described, the agents including a selective inhibitor of inducible nitric oxide synthase and a combination of a selective inhibitor of inducible nitric oxide synthase and an inhibitor of cylcooxygenase-2 in a pharmaceutical composition. The agents and methods are used for chemoprevention and treatment of neoplasia including colorectal cancer and other cancers affecting epithelial cells throughout the body. The agents can also be used to treat the fibrosis that occurs with radiation therapy, as well as adenomatous polyps, including those with familial adenomatous polyposis (FAP).
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- THERAPEUTIC COMBINATIONS FOR CARDIOVASCULAR AND INFLAMMATORY INDICATIONS
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The present invention provides therapeutic combinations and methods for treating or preventing a hypercholesterolemia-related or an inflammation-related condition in a subject in need of such treatment or prevention. One therapeutic combination comprises
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- Method for the treatment and prevention of cachexia
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Cachexia, including anorexia and other forms of weight loss, is a frequent complication of acute and chronic infections, and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. The present invention includes methods for the treatment or prevention of cachexic conditions while maintaining the production of factors essential for infection control through the administration of an effective amount of a cyclooxygenase-2 selective inhibiting compound.
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- Reinvestigation of mucohalic acids, versatile and useful building blocks for highly functionalized alpha,beta-unsaturated gamma-butyrolactones.
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[reaction: see text] Mucohalic acids (mucochloric acid (1, 3,4-dichloro-5-hydroxy-5H-furan-2-one) and mucobromic acid (2, 3,4-dibromo-5-hydroxy-5H-furan-2-one)) are inexpensive, commercially available starting materials with multiple functional groups. These compounds have been modified by way of reduction followed by Suzuki cross-coupling reactions involving arylboronic acids to afford highly functionalized alpha,beta-unsaturated gamma-butyrolactones in excellent yield. The synthetic utility of these building blocks was effectively demonstrated through preparation of the antiinflammatory drug Vioxx.
- Zhang,Blazecka, Peter G,Belmont, Daniel,Davidson, James G
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p. 4559 - 4561
(2007/10/03)
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- Method of treating cancer
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The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and an NSAID compound, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and an NSAID compound. The invention also relates to methods of preparing such compositions.
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- Antiangiogenic combination therapy for the treatment of cancer
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The present invention provides combinations of a DNA topoisomerase I inhibiting agent and a selective COX-2 inhibiting agent for preventing, treating, and/or reducing the risk of developing a neoplasia disorder in a mammal.
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- Use of selective COX-2 inhibitors for the treatment of urinary incontinence
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The treatment of neuromuscular dysfunction of the lower urinary tract by compounds which selectively inhibit the COX-2 isozyme is described. The compounds concerned inhibit the COX-2 isozyme with a potency at least 10-fold, and preferably at least 100-fold, greater than their potency on the COX-1 isozyme.
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- Synthesis of Rofecoxib, (MK 0966, Vioxx 4-(4′-Methylsulfonylphenyl)-3-phenyl-2(5H)-furanone), a selective and orally active inhibitor of cyclooxygenase-2
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The synthesis of Vioxx (Rofecoxib, MK 966, 4-(4′methylsulfonylphenyl)-3-phenyl-2(5H)-furanone), a newly FDA approved inhibitor of cyclooxygenase-2, is described.
- Therien,Yves Gauthier,Leblanc,Leger,Perrier,Prasit,Wang
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p. 1778 - 1779
(2007/10/03)
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- Diaryl-2-(5H)-furanones as Cox-2 inhibitors
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The invention encompasses the novel compound of Formula (I) as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula (I). The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula (I).
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- Compositions for a once day treatment of cyclooxygenase-2 mediated diseases
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PCT No. PCT/US97/08041 Sec. 371 Date Mar. 8, 1999 Sec. 102(e) Date Mar. 8, 1999 PCT Filed May 13, 1997 PCT Pub. No. WO97/44028 PCT Pub. Date Nov. 27, 1997This application relates to a method of treating a disease susceptible to treatment with a non-steroidal anti-inflammatory drug by administering to a patient once daily an effective amount of 3-phenyl-4-(4-methylsulfonyl)phenyl)-2-(5H)-furanone.
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- Magnesium mediated carbometallation of propargyl alcohols: Direct routes to furans and furanones
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The addition of vinyl and aryl Grignard reagents to propargyl alcohols for the direct synthesis of furans and butenolides from a one pot reaction is described. These products arise from a putative magnesium chelate intermediate 2 upon reaction with various electrophiles. This chelate was also generated in situ from alkynyl lithium addition to aldehydes followed by magnesium exchange and Grignard addition. Thus, the complete substitution pattern for the furan ring may be controlled, as desired, through the judicious choice of substrates and reagents.
- Forgione, Pat,Wilson, Peter D.,Fallis, Alex G.
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-
- Selective synthesis of unsymmetrical 3,4-disubstituted and 4-substituted 2(5H)-furanones
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Easily available 3,4-dibromo-2(5H)-furanone undergoes regioselective palladium-catalyzed reaction with aryl(trialkyl)stannanes to give the corresponding 4-aryl-3-bromo-2(5H)-furanones in satisfactory yields. These monobromo derivatives have proven to be useful precursors to unsymmetrical 3,4-diaryl-2(5H)-furanones, 4-aryl-3-methyl-2(5H)-furanones and 4-aryl-2(5H)-furanones.
- Rossi,Bellina,Raugei
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p. 1749 - 1752
(2007/10/03)
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- Method of treating colonic adenomas
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This invention is directed to a method of retarding or preventing the transformation of a colonic adenoma to a colonic adenocarcinoma comprising the administration to a patient with FAP or a patient with one or more of said adenomas a non-toxic therapeutically effective amount of NSAID, said amount effective to inhibit the PGHS-2 in said adenoma. The preferred method comprises the administration of a specific PGHS-2 inhibiting agent as defined herein.
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- Phenyl heterocycles as cox-2 inhibitors
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The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
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- Use of inhibitors of cyclooxygenase in the treatment of neurodegenerative diseases
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The present invention provides a method of treating a neurodegenerative disease and in particular Alzheimers disease which comprises administering to a human in need thereof a therapeutically effective amount of a non-steroid COX-II inhibitor. Although a wide range of COX-II inhibitors may be employed but it is preferred to employ compounds of the Formula I: STR1
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- Stilbene derivatives useful as cyclooxygenase-2 inhibitors
-
The invention encompasses novel compounds of Formula Iuseful in the treatment of cyclooxygenase-2 mediated diseases. STR1 The invention also encompasses certain pharmaceuticalcompositions and methods for treatment of cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I.
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- Diaryl-5-oxygenated-2-(5H) -furanones as COX-2 inhibitors
-
The invention encompasses the novel compound of Formula I as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula I. STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
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- Method of preventing bone loss
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The invention encompasses a method of inhibiting bone resorption in patients in need of such inhibition to a degree sufficient to halt or retard loss of bone mass, reduce fractures, improve bone repair and prevent or treat osteoporosis comprising: the administration of a non-toxic therapeutically effective amount of a selective cyclooxygenase-2 inhibitor such as the compounds of formula I. STR1 The invention also encompasses certain pharmaceutical compositions for the purposes described above.
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- Process of making cox-2 inhibitors having a lactone bridge
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The invention encompasses a process for making compounds of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. STR1
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- Phenyl heterocycles as cox-2 inhibitors
-
The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases, STR1 The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.
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