cas 181695-72-7, VALDECOXIB | Articles data

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NHC-palladium-catalyzed ionic liquid-accelerated regioselective oxyarylation of alkynes with diaryl ethers?
The first NHC-palladium-catalyzed regioselective oxyarylation of oxime ether in a task-specific ionic liquid via C(sp3)-O and C(sp2)-O bond cleavage of two different types of ethers for the assembly of structurally diverse 4-arylisoxazoles is described. Both the basic ionic liquid [C3NH2mim]Br and NHC-Pd catalyst IPr-Pd-Im-Cl2 played an important role in this transformation. Notably, this new approach provides a practical and straightforward route to access a broad range of privileged 4-arylisoxazole structures with good yields and excellent regioselectivities. Significantly, this catalytic system can be recycled up to eight times without significant loss of catalytic activity.
Cen, Liying,He, Dan,Jiang, Huanfeng,Li, Jianxiao,Lin, Zidong,Wu, Wanqing
p. 1983 - 1988
(2022/04/03)

Preparation method of parecoxib sodium
The invention belongs to the technical field of parecoxib sodium production and provides a preparation method of parecoxib sodium, which comprises the following steps: (1) carrying out sulfonation reaction on acetophenone and chlorosulfonic acid to obtain an intermediate (I) 1-phenyl-2-(4-sulfonyl chloride phenyl)acetophenone; (2) carrying out acetylation reaction on the intermediate I and acetyl chloride to obtain an intermediate (II) 1-phenyl-2-(4-sulfonyl chloride phenyl)-2-acetyl ethanone; (3) refining the intermediate II; (4) carrying out cyclization reaction on the refined intermediate II and hydroxylamine hydrochloride to obtain an intermediate III 4-(5-methyl-3-phenyl-4-isoxazole)benzenesulfonyl chloride; (5) carrying out ammoniation reaction on the intermediate III and ammonia water to obtain an intermediate IV 4-(5-methyl-3-phenyl-4-isoxazole)benzenesulfonamide; (6) carrying out propionylation reaction on the intermediate IV and propionic anhydride to obtain parecoxib; and (7) carrying out salt forming reaction on the intermediate V and sodium hydroxide to obtain the parecoxib sodium. The technical problems that an existing parecoxib sodium synthesis method is complex in reaction process and high in production cost are solved.
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Paragraph 0025; 0030; 0033; 0038; 0041; 0046

(2021/04/17)

Parecoxib sodium, injection preparation and preparation method
The invention discloses parecoxib sodium, an injection preparation and a preparation method. The preparation method of the parecoxib sodium is as follows: 5-methyl-3,4-diphenylisoxazole is used as theraw material; sulfonation and amination are carried out in sequence, so that a valdecoxib intermediate is obtained; then, the valdecoxib intermediate is subjected to acylation reaction and salt forming reaction, so that crude parecoxib sodium is obtained; the crude parecoxib sodium is dissolved and decolourized, so that the finished parecoxib sodium is obtained; the finished parecoxib sodium is the parecoxib sodium A crystal form; and the parecoxib sodium preparation for injection is prepared by adding accessories into the parecoxib sodium A crystal form. The preparation method of the parecoxib sodium in the invention is simple in synthetic route and moderate in reaction condition; raw materials are available at low prices; and furthermore, the impurity content of the prepared parecoxib sodium is low.
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Paragraph 0052-0059; 0087

(2020/12/08)

Preparation method of parecoxib sodium
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of parecoxib sodium. 5-methyl-3, 4-diphenyl isoxazole is used as a raw material, and the parecoxib sodium is obtained through sulfonation reaction, ammoniation reaction, propionylation reaction and salification. The method has the advantages of mild reaction, easy operation, great reductionof the generation of HCl gas, short reaction time, high product yield, and suitableness for industrial production.
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(2020/05/14)

A handkerchief auspicious past cloth sodium freeze-dried powder, its preparation method and its powder products
The invention discloses a parecoxib sodium freeze-dried powder, a preparation method and a powder product thereof. The freeze-dried powder comprises 95-100 wt% of the parecoxib sodium and 0-5 wt% of a pH regulator; or 40-100 wt% of the parecoxib sodium and 0-60 wt% of L-malate. The freeze-dried powder has simple preparation method, is free of auxiliary materials or employs few auxiliary materials, is reduced in cost, and satisfies national medicine standards in storage stability, clinical application stability and safety.
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(2019/06/11)

Preparation method of parecoxib sodium
The invention belongs to the technical field of drug preparation, and specifically relates to a preparation method of parecoxib sodium. The preparation method comprises sulfonation reactions, amination reactions, propionylation reactions, and salt forming reactions. In sulfonation reactions, 5-methyl-3,4-diphenyl isoxazole is taken as the primary raw material and directly carries out reactions with chlorosulfonic acid, after reactions, and the reaction system is poured into water to carry out quenching to obtain suspension of reaction products. All used reagents are common reagents; the preparation method only uses third kind solvents, which are regulated by International Council for Harmonization (ICH) and are harmless for human body; the operation of the preparation method and post treatment is simple, the repeatability is good, the yield is high, and the cost is low. The purity of prepared parecoxib sodium can reach 99.9% or more. The quality of prepared parecoxib sodium is higher than the standards made by a plant that develops parecoxib sodium. The preparation method is suitable for industrial production of pharmaceutical enterprises.
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(2019/10/04)

Valdecoxib and synthesis method thereof
The invention belongs to the technical field of medicine, and particularly relates to vardicoxib and a synthesis method thereof. The synthesis method includes the steps that: taking acetone and pyrrolidine as initial raw materials for sequential multiple reactions; and carrying out washing, drying, filtering and evaporating to obtain vadicoxib. According to the synthesis method of vardicoxib, acetone and pyrrolidine are selected as the initial raw materials; a plurality of reactions with subsequently added reaction products are carried out to obtain to obtain vardicoxib through synthesis at last; reaction conditions (such as the reaction conditions, reactant adding time, reaction temperature, heating reflux time and the like) of each reaction are controlled, so that the reaction rate can be effectively increased, and the reaction time is shortened; by reasonably setting the component content ratio of each raw material, the purity and yield of the product can be effectively improved; and in conclusion, the synthesis method of the vadicoxib is short in reaction time, the raw materials are easy to obtain and low in price, the purity of the final product reaches up to 99.538%, the yield reaches up to 95.7%, and industrial production is facilitated.
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Paragraph 0055; 0057-0062; 0064-0069; 0071-0075

(2019/12/25)

Bone-targeted parecoxib sodium nanocapsule freeze-dried injection and preparation method thereof
The invention discloses a bone-targeted nanocapsule freeze-dried injection containing parecoxib sodium and a preparation method of the injection. By virtue of a preparation, namely the injection, the concentration of parecoxib sodium in a bone tissue can be increased, so that the effects of parecoxib sodium in orthopedic surgeries and bone cancer analgesia are improved. By utilizing a capsule material and a carrier material which have good biodegradability and biocompatibility, a drug can be tightly combined with soft and hard tissues in a human body in a short time after entering the human body so as to rapidly play a role of treatment. By utilizing a nanocapsule packaging manner, the content of degradation products of the preparation is extremely low.
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(2017/10/25)

A process for the preparation of sodium compound handkerchief auspicious past cloth and wherein the intermediate impurity, preparation method and application
The invention provides parecoxib sodium which is prepared by controlling an intermediate impurity and in particular provides a preparation method of a parecoxib sodium compound as well as the intermediate impurity and an application of the parecoxib sodium compound. According to the preparation method provided by the invention, 3-methyl-4,5-diphenyl-4,5-dihydro-isoxazole-5-alcohol is used as an isomer impurity for preparing 5-methyl-3,4-diphenyl-4,5-dihydro-isoxazole-5-alcohol as an intermediate of the parecoxib sodium, the quality of the 3-methyl-4,5-diphenyl-4,5-dihydro-isoxazole-5-alcohol is controlled in the preparation of the parecoxib sodium, specifically, the impurity content is required not to be higher than 0.5 percent, and an important significance is provided for the product quality of the parecoxib sodium; by obtaining the 3-methyl-4,5-diphenyl-4,5-dihydro-isoxazole-5-alcohol as an isomer impurity of the important 5-methyl-3,4-diphenyl-4,5-dihydro-isoxazole-5-alcohol and further studying 3-methyl-4,5-diphenyl-4,5-dihydro-isoxazole-5-alcohol in the aspects of preparation process, detection process and purification process, important quality monitoring significance is provided for the process with the 5-methyl-3,4-diphenyl-4,5-dihydro-isoxazole-5-alcohol as an industrial production raw material.
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(2017/02/24)

Method for preparing parecoxib for treating postoperative pain
The invention discloses a method for preparing parecoxib for treating postoperative pain. The method comprises the following steps: 1) conducting a contact reaction between 3,4-diphenyl-4-(1-pyrrolidyl)-3-butene-2-one and ammonium acetate in acetic acid; after the reaction, diluting dichloromethane; regulating the pH value to 6-7 with saturated sodium bicarbonate; concentrating the organic phase and washing; recrystallizing with ethanol; and drying to obtain 5-methyl-3,4-diphenyl isoxazole; 2) stirring the obtained 5-methyl-3,4-diphenyl isoxazole and chlorosulfonic acid for reacting; adding anion exchange resin, and dropwise adding saturated ammonium chloride and dichloromethane for extraction; washing and concentrating; and recrystallizing with ethanol to obtain valdecoxib; and 3) enabling the valdecoxib obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The method for preparing parecoxib, disclosed by the invention, has the advantages of simple steps, mild conditions and high yield.
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Paragraph 0021; 0044; 0045; 0046

(2017/01/12)

Preparation method of cyclooxygenase-2 inhibitor parecoxib
The invention discloses a preparation method of a cyclooxygenase-2 inhibitor parecoxib. The method comprises the following steps that 1, benzaldoxime reacts with 1-phenylpropyne in the presence of tris(2-phenylpyridine)iridium (III), triethylamine and magnesium oxide under the illumination condition to obtain 5-methyl-3,4-diphenylisoxazole; 2, a stirring reaction is conducted on 5-methyl-3,4-diphenylisoxazole obtained in the first step and chlorosulfonic acid, dichloromethane extraction is conducted after the reaction is completed, a dichloromethane phase is directly added into ammonium hydroxide, an organic phase is separated, water washing, concentrating and ethanol recrystallization are conducted, and valdecoxib is obtained; 3, valdecoxib obtained in the second step reacts with propionic anhydride in the presence of triethylamine, and parecoxib is obtained. The preparation method of parecoxib is simple in step, high in yield and simple in posttreatment.
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Paragraph 0045; 0046; 0047

(2016/11/14)

Preparing method for parecoxib sodium
The invention belongs to the field of medicine chemical industry and particularly relates to a preparing method for parecoxib sodium. According to the method, benzaldoxime (compound I) and 1-phenyl-1-propyne (compound II) are subjected to an addition reaction under existence of a catalyst and an acid-binding agent to construct an isoxazole ring to obtain a parecoxib sodium intermediate (compound III); the compound III is subjected to a sulfonation and sulfonylation reaction to obtain a compound IV, and the compound IV and propionic anhydride react to form salt to obtain parecoxib sodium (compound V). According to the method, the dipole ring addition reaction is creatively adopted for preparing the compound III, common safe and low-toxicity reagents chlorosulfuric chlorosulfonic acid and ammonia water with relative stable nature are used to be subjected to the sulfonylation reaction, and the method has the advantages that the reaction condition is mild, operation is reasonable, selectivity is high, and product quality is high; raw and auxiliary materials in the reaction are low in price, and the production cost is reduced.
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Paragraph 0063; 0064

(2016/10/08)

A method of preparing intermediates handkerchief auspicious past cloth sodium
The invention discloses a novel method for preparing a parecoxib sodium intermediate 5-methyl-3, 4-diphenyl isoxazole. The method comprises the following steps: performing rearrangement reaction on a compound in the formula I (referring to the Specification)under the action of a catalyst to prepare a compound in the formula II(referring to the Specification); and under the condition of a catalyst, reacting hydroxylammonium chloride with the compound in the formula II to prepare 5-methyl-3,4-diphenyl isoxazole. The method disclosed by the invention has the advantages of mild reaction condition, good simplicity and convenience for operation, low cost, environmental-friendliness and the like.
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Paragraph 0032-0035

(2017/05/05)

Oxyboration with and without a Catalyst: Borylated Isoxazoles via B-O-Bond Addition
Herein we report an oxyboration reaction with activated substrates that employs B-O σ bond additions to C-C π bonds to form borylated isoxazoles, which are potential building blocks for drug discovery. Although this reaction can be effectively catalyzed by gold, it is the first example of uncatalyzed oxyboration of C-C π bonds by B-O σ bonds-and only the second example that is catalyzed. This oxyboration reaction is tolerant of groups incompatible with alternative lithiation/borylation and palladium-catalyzed C-H activation/borylation technologies for the synthesis of borylated isoxazoles.
Tu, Kim N.,Hirner, Joshua J.,Blum, Suzanne A.
p. 480 - 483
(2016/02/18)

Method for preparing cyclooxygenase-2 inhibitor parecoxib
The invention discloses a method for preparing a cyclooxygenase-2 inhibitor parecoxib. The method comprises the following steps: 1) enabling benzaldoxime and 1-(4-sulfonyl phenyl)propyne to react in an illumination condition in the presence of tri(2-phenylpyridine)iridium (III), triethylamine and magnesium oxide to obtain 5-methyl-3-phenyl-4-(4-sulfonyl phenyl)isoxazole; 2) conducting a contact reaction between 5-methyl-3-phenyl-4-(4-sulfonyl phenyl)isoxazole obtained in the step 1) and thionyl chloride; after the reaction, extracting dichloromethane; directly adding the dichloromethane phase into ammonia water; separating organic phase; washing and concentrating; and recrystallizing with ethanol to obtain valdecoxib; and 3) enabling the valdecoxib obtained in the step 2) to react with propionic anhydride in the presence of triethylamine to obtain parecoxib. The parecoxib preparation method disclosed by the invention has the advantages of simple steps, high yield and simple aftertreatment.
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(2017/01/02)

Oxime-mediated facile access to 5-methylisoxazoles and applications in the synthesis of valdecoxib and oxacillin
A palladium-catalyzed efficient synthesis of 5-methylisoxazoles via oxime-mediated functionalization of unactivated olefins is described. The reaction affords a variety of 5-methylisoxazoles in moderate to good yields. To further demonstrate the utility of the method, the rapid synthesis of valdecoxib and oxacillin is reported. (Chemical Equation Presented).
Dong, Kui-Yong,Qin, Hai-Tao,Bao, Xing-Xing,Liu, Feng,Zhu, Chen
p. 5266 - 5268
(2015/01/09)

Application of [3+2]-cycloaddition in the synthesis of valdecoxib
A large scale synthesis of valdecoxib 1 is described. Our work features potential application of [3+2]-dipolar cycloaddition involving enamine and in situ-generated nitrile oxide derivatives. Dr. Reddy's Laboratories Ltd.
Reddy, Anumula Raghupathi,Goverdhan, Gilla,Sampath, Aalla,Mukkanti, Khagga,Reddy, Padi Pratap,Bandichhor, Rakeshwar
p. 639 - 649
(2012/01/13)

CO-CRYSTALS OF TRAMADOL AND COXIBS
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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(2012/07/14)

Iodocyclization of hydroxylamine derivatives based on the control of oxidative aromatization leading to 2,5-dihydroisoxazoles and isoxazoles
An efficient method for the synthesis of 2,5-dihydroisoxazoles and isoxazoles using iodocyclization of N-alkoxycarbonyl O-propargylic hydroxylamines has been developed. 2,5-Dihydro-4-iodoisoxazole underwent the cross-coupling reactions without aromatization to afford polyfunctionalized 2,5-dihydroisoxazoles. This process was applied to the preparation of valdecoxib and its 2,5-dihydro-derivative.
Okitsu, Takashi,Sato, Kana,Potewar, Taterao M.,Wada, Akimori
experimental part
p. 3438 - 3449
(2011/06/26)

The synthesis of highly substituted isoxazoles by electrophilic cyclization: An efficient synthesis of valdecoxib
(Chemical Equation Presented) A large number of functionally substituted 2-alkyn-1-one O-methyl oximes have been cyclized under mild reaction conditions in the presence of ICl to give the corresponding 4-iodoisoxazoles in moderate to excellent yields. The resulting 4-iodoisoxazoles undergo various palladium-catalyzed reactions to yield 3,4,5-trisubstituted isoxazoles, including valdecoxib.
Waldo, Jesse P.,Larock, Richard C.
p. 9643 - 9647
(2008/03/17)

BIOSYNCHRONOUS TRANSDERMAL DRUG DELIVERY
Systems and methods for treating diseases, addictions and disorders in humans and animals involving synchronizing and tailoring the administration of drug compounds with the body's natural circadian rhythms, in order to counteract symptoms when they are likely to be at their worst. Automated and pre programmable transdermal drug administration system are used. This system can also utilize a pump or pressurized reservoir, and/or a system for removing depleted carrier solution, or other modulated dispensing actuator, in conjunction with micro-fabricated structures commonly referred to as Micro-needles, or heat, or iontophoresis, sonophoresis, or a wide range of chemical permeation enhancers.
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(2008/06/13)

METHOD FOR THE PREVENTION OR TREATMENT OF PAIN, INFLAMMATION, AND INFLAMMATION-RELATED DISORDERS WITH A COX-2 SELECTIVE INHIBITOR IN COMBINATION WITH A NITRIC OXIDE-DONATING AGENT AND COMPOSITIONS THEREWITH
Methods and compositions are described for the prevention or treatment of pain, inflammation, and inflammation-related disorders in a subject in need of such prevention or treatment, the method comprising administering to the subject a cyclooxygenase-2 selective inhibitor in combination with a nitric oxide-donating agent. Also described are therapeutic and pharmaceutical compositions and kits that are useful in the present invention.
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Page/Page column 73-74

(2008/06/13)

Method for preparing 3,4-diphenyl-substituted isoxazole compounds
The present invention relates to a process for preparing diaryl-substituted isoxazole using compounds of Formula (V) and Formula (VII): where Y is and to processes for preparing valdecoxib and parecoxib.
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Page/Page column 9

(2008/06/13)

Process for preparing crystalline form A of valdecoxib
Valdecoxib Form A is prepared by a process comprising adding aqueous ammonia to a solution of 4-(5-methyl-3-phenyl-4-isoxazolyl)benzenesulfonyl chloride in a halogenated hydrocarbon or water.
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Page/Page column 2

(2008/06/13)

METHOD FOR THE PREPARATION OF DIARYLISOXAZOLE SULFONAMIDE COMPOUNDS AND INTERMEDIATES
The disclosure provides a method for the preparation of a diarylisoxazolé sulfonamide compound comprising contacting a deoxybenzoin with a secondary amine to form a diarylenamine compound; contacting the diarylenamine compound with an acetylating agent to form an acetyl diarylenamine compound; contacting the acetyl diarylenamine compound with a source of hydroxylamine to form an diaryl isoxazolol compound; eliminating water from the diaryl isoxazolol compound to form a diaryl isoxazole compound, chlorosulfonating the diarylisoxazole compound to form a chlorosulfonyl diaryl isoxazole compound; and contacting the chlorosulfonyl diaryl isoxazole compound with a source of ammonia to form the diarylisoxazole sulfonamide compound.
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Page/Page column 38-39

(2008/06/13)

A NOVEL PROCESS FOR PREPARING VALDECOXIB
The present invention relatesto a novel process for making 4-[5-methyl -3-phenylisoxazol-4-yl] benzenesulphonamide
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Page/Page column 10

(2008/06/13)

Investigation of the scope of a [3+2] cycloaddition approach to isoxazole boronic esters
The [3+2] cycloaddition reaction of nitrile oxides and alkynylboronates provides direct access to a wide variety of isoxazole boronic esters. Specifically, this technique has been employed to generate trisubstituted isoxazole 4-boronates and disubstituted isoxazoles where the boronic ester moiety can be installed at C-4 or C-5 with high levels of regiocontrol. The application of this methodology in the synthesis of non-steroidal antiinflammatory agents is also described.
Moore, Jane E.,Davies, Mark W.,Goodenough, Katharine M.,Wybrow, Robert A. J.,York, Mark,Johnson, Christopher N.,Harrity, Joseph P. A.
p. 6707 - 6714
(2007/10/03)

Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin D derivatives and a cyclooxgenase-2 inhibitor
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)

Novel synthesis of 3,4-diarylisoxazole analogues of valdecoxib: Reversal cyclooxygenase-2 selectivity by sulfonamide group removal
3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol- 4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition of arylnitrile oxides to the enolate ion of phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 °C. The corresponding 3-aryl-5-methyl-4-phenyl- isoxazoles were easily generated by a dehydration/aromatization reaction under basic conditions of 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines and further transformed into their benzenesulfonamide derivatives. The biochemical COX-1/COX-2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity. Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX-1 inhibitors.
Di Nunno, Leonardo,Vitale, Paola,Scilimati, Antonio,Tacconelli, Stefania,Patrignani, Paola
p. 4881 - 4890
(2007/10/03)

METHOD OF USING CYCLOOXYGENASE-2 INHIBITORS IN THE TREATMENT AND PREVENTION OF NEOPLASIA
This invention relates to the use of cyclooxygenase-2 inhibitors or derivatives thereof in preventing and treating neoplasia. In particular, the invention describes the method of preventing and treating epithelial cell neoplasia in a subject, said method comprising treating the subject with a therapeutically-effective amount of a compound of Formula (I) wherein A, R and R are as described in the specification.
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(2008/06/13)

Method of using cyclooxygenase-2 inhibitors in maintaining the fetal ductus ateriosus during treatment and prevention of preterm labor
This invention relates to the use of a tocolytic agent or agents in combination with selective cyclooxygenase-2 inhibitors of Formula (II) or a pharmaceutically-acceptable salt or derivative thereof for preparing a medicament for maintaining circulation through fetal ductus arteriosus during treatment or prevention of preterm labor in a subject in need of such treatment or prevention.
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(2008/06/13)

Use of a COX-2 inhibitor and a NK-1 receptor antagonist for treating inflammation
The present invention provides the use of a COX-2 inhibitior and an NK-1 receptor antagonist for the treatment or prevention of inflammatory disorders.
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(2008/06/13)

Crystalline parecoxib sodium
Parecoxib sodium is provided in a crystalline form that is substantially anhydrous and substantially nonsolvated. Various such anhydrous, nonsolvated crystal forms have been identified, including Forms A, B and E as described herein. Also provided is a parecoxib sodium drug substance wherein at least about 90% of the parecoxib sodium is in one or more anhydrous, nonsolvated crystal forms. Such a drug substance is a storage-stable intermediate that can be further processed, for example by dissolution or slurrying in an aqueous medium together with one or more parenterally acceptable excipients, followed by lyophilization of the resulting solution or slurry to provide a reconstitutable injectable composition suitable for therapeutic use.
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Page 5

(2008/06/13)

Method for preparing benzenesulfonyl compounds
The present disclosure provides a method for the preparation of aromatic sulfonyl halides by contacting a substituted phenyl compound with a halosulfonic acid and trifluoroacetic acid. The present disclosure further provides a method for the preparation of 4-[5-methyl-3-phenylisoxazol-4-yl]benzenesulfonamide which is useful in treating cyclooxygenase-2 related disorders.
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(2008/06/13)

Agents and methods for treatment of cancer
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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(2008/06/13)

THERAPEUTIC COMBINATIONS FOR CARDIOVASCULAR AND INFLAMMATORY INDICATIONS
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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(2008/06/13)

Method for the treatment and prevention of cachexia
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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(2008/06/13)

Substituted isoxazoles for the treatment of inflammation
A class of substituted isoxazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula (III) wherein R7 is selected from hydroxyl, lower alkyl, carboxyl, halo, lower carboxylalkyl, lower alkoxycarbonylalkyl, lower alkoxyalkyl, lower carboxyalkoxyalkyl, lower haloalkyl, lower haloalkylsulfonyloxy, lower hydroxyalkyl, lower aryl (hydroxylalkyl), lower carboxyaryloxyalkyl, lower alkoxycarbonylaryloxyalkyl, lower cycloalkyl, lower cycloalkylalkyl, and lower aralkyl; and wherein R8 is one or more radicals independently selected from hydrido, lower alkylsulfinyl, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, lower haloalkyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, lower arylamino, lower aminoalkyl, nitro, halo, lower alkoxy, aminosulfonyl, and lower alkylthio; or a pharmaceutically-acceptable salt thereof.
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(2010/11/30)

Convenient Approach to 3,4-Diarylisoxazoles Based on the Suzuki Cross-Coupling Reaction
The Suzuki cross-coupling reaction was found effective for rapid access to a series of 3,4-diarylisoxazoles of pharmacological interest. The efficiency of this approach was demonstrated by the synthesis of the highly potent COX-2-selective inhibitor, 4-(5-methyl-3-phenyl-4-isoxazolyl)benzenesulfonamide (valdecoxib), and its analogues. Thus, the coupling reaction between (3-aryl-5-methyl-4-isoxazolyl)boronic acids, prepared in situ from the corresponding bromides using triisopropyl borate, and aryl bromides containing a 4-sulfonamide or 4-methylsulfonyl group under the standard conditions [Pd(PPh3)4, Na2CO3, EtOH-H2O, reflux] yielded the target 3,4-diarylisoxazoles in good yields.
Dileep Kumar,Ho, ManKit M.,Leung, Jennifer M.,Toyokuni, Tatsushi
p. 1146 - 1151
(2007/10/03)

Combination therapy in the prevention of cardiovascular disorders
This invention relates to the use of cyclooxygenase-2 inhibitors or derivatives thereof in preventing cardiovascular disorders.
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(2008/06/13)

Combination therapy using COX-2 selective inhibitor and thromboxane inhibitor and compositions therefor
The present invention provides a method for the treatment or prophylaxis of COX-2-mediated conditions in patients who are at risk of developing thromboembolic events which comprises administering to said patient a therapeutically or prophylactically effective amount of a COX-2 selective inhibitor and a cardiovascular protective amount of a thromboxane inhibitor, as well as compositions therefor.
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(2008/06/13)

Antiangiogenic combination therapy for the treatment of cancer
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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(2008/06/13)

Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor
A method to suppress immune, acute or delayed-type hypersensitivity by treatment with a combination of a therapeutically-effective amount of a 5-lipoxygenase inhibitor and a cyclooxygenase-2 inhibitor is reported. The method may be used, for example, to suppress the immune response associated with organ transplantation, graft versus host disease, and conditions with underlying autoimmune or inflammatory reactivities or responses.
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(2008/06/13)

Immunosuppressive effects of administration of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor
Treatment with a cyclooxygenase-2 inhibitor and a leukotriene A4hydrolase inhibitor is described as being useful in reducing recipient rejection of transplanted organs and for treatment of autoimmnune diseases.
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(2008/06/13)

Use of selective COX-2 inhibitors for the treatment of urinary incontinence
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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(2008/06/13)

Combination of a GABAA alpha 5 inverse agonist and COX-2 inhibitor, NSAID, estrogen or vitamin E
Combinations of a GABAAalpha 5 inverse agonist and a COX-2 inhibitor, NSAID, estrogen or vitamin E are disclosed for treating neurodegenerative conditions such as Alzheimer's Disease.
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(2008/06/13)

Combination therapy for treating neurodegenerative disease
The instant invention provides a novel drug combination comprised of an HMG-CoA reductase inhibitor and a selective COX-2 inhibitor, which is useful for treating, preventing, delaying the onset of and/or reducing the risk of developing Alzheimer's disease. One object of the instant invention is to administer the above-described combination therapy to people who do not yet show clinical signs of Alzheimer's disease, but who are at risk of developing Alzheimer's disease. These individuals may already show signs of mild cognitive impairment. Toward this end, the instant invention provides methods for preventing or reducing the risk of developing Alzheimer's by administering the above-described combination therapy to said at risk persons. Such treatment may halt or reduce the rate of further cognitive decline or, in fact, reverse cognitive decline. The present invention also provides for a method of preventing cognitive impairment or dementia, reducing the risk of cognitive decline or impairment or reducing cognitive decline or impairment resulting from stroke, stroke, cerebral ischemia or de-myelinating disorders.
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(2008/06/13)

Crystalline form of 4- [ 5-methyl-3-phenylisoxazol-4-yl ] benzenesulfonamide
A stable crystalline form of 4-[5-methyl-3-phenylisoxazol-4-yl]benzenesulfonamide is described. This crystal structure, designated Form B, is more stable, has favorable handling properties and is characterized by its melting point, x-ray and other physical characterizations.
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(2008/06/13)

Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) inhibitors, H antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.
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(2008/06/13)

Combination therapy for reducing the risks associated with cardio-and-cerebrovascular disease
The instant invention provides a drug combination comprised of an HMG-CoA reductase inhibitor in combination with a COX-2 inhibitor, which is useful for treating, preventing, and/or reducing the risk of developing atherosclerosis and atherosclerotic disease events.
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(2008/06/13)