- Annulation of ketones with vinamidinium hexafluorophosphate salts: an efficient preparation of trisubstituted pyridines.
-
alpha-Aryl ketones react with vinamidinium hexafluorophosphate salts to give access to the corresponding 3-arylpyridines. The annulation reactions proceed in good to excellent yields with vinamidinium salts containing electron-withdrawing groups at the beta-position (R(2)). The reaction was applied to the preparation of the COX-2 specific inhibitor 5-chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine (1), as well as a series of analogues.
- Marcoux,Corley,Rossen,Pye,Wu,Robbins,Davies,Larsen,Reider
-
-
Read Online
- Access to pyridines via cascade nucleophilic addition reaction of 1,2,3-triazines with activated ketones or acetonitriles
-
We studied the cascade nucleophilic addition reactions of 1,2,3-triazines with activated acetonitriles or ketones, which were used to construct highly substituted pyridines that are not easily accessed by conventional methods. The strategy addressed some structural diversity issues currently facing medicinal chemistry, and the resulting pyridines could be used as convenient precursors for the synthesis of related pharmaceuticals. In particular, our method was applied to the syntheses of the marketed drug etoricoxib and several biologically important molecules in a few steps.
- Zhang, Yuan,Luo, Han,Lu, Qixing,An, Qiaoyu,Li, You,Li, Shanshan,Tang, Zongyuan,Li, Baosheng
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supporting information
p. 393 - 396
(2020/05/18)
-
- Mechanochemical Solvent-Free Catalytic C?H Methylation
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The mechanochemical, solvent-free, highly regioselective, rhodium-catalyzed C?H methylation of (hetero)arenes is reported. The reaction shows excellent functional-group compatibility and is demonstrated to work for the late-stage C?H methylation of biologically active compounds. The method requires no external heating and benefits from considerably shorter reaction times than previous solution-based C?H methylation protocols. Additionally, the mechanochemical approach is shown to enable the efficient synthesis of organometallic complexes that are difficult to generate conventionally.
- Ni, Shengjun,Hribersek, Matic,Baddigam, Swarna K.,Ingner, Fredric J. L.,Orthaber, Andreas,Gates, Paul J.,Pilarski, Lukasz T.
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supporting information
p. 6660 - 6666
(2020/12/18)
-
- Synergistic cooperative effect of CF3SO2Na and bis(2-butoxyethyl)ether towards selective oxygenation of sulfides with molecular oxygen under visible-light irradiation
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A safe, practical and eco-friendly method for the switchable synthesis of sulfoxides and sulfones through visible-light-initiated oxygenation of sulfides at ambient temperature under transition-metal-, additives-free and minimal solvent conditions. The synergistic catalytic efforts between CF3SO2Na and 2-butoxyethyl ether represents the key promoting factor for the reaction. This journal is
- Liu, Kai-Jian,Wang, Zheng,Lu, Ling-Hui,Chen, Jin-Yang,Zeng, Fei,Lin, Ying-Wu,Cao, Zhong,Yu, Xianyong,He, Wei-Min
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p. 496 - 500
(2021/01/28)
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- Highly Selective Room-Temperature Suzuki-Miyaura Coupling of Bromo-2-sulfonyloxypyridines for Unsymmetrical Diarylpyridines
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A new and mild synthetic approach has been developed for the synthesis of pharmaceutically important unsymmetrical diarylpyridines via chemoselective Suzuki-Miyaura coupling reactions of bromo-2-sulfonyloxypyridines. Most reactions allow for facile access to aryl-2-sulfonyloxypyridines at room temperature in yields of 5-99% with excellent chemoselectivity in the presence of Pd(OAc)2 (2.0 mol %) and Ad2BnP (2.4 mol %). The second arylation of the remaining tosyl or triflyl group in the monoarylpyridine derivatives obtained was successfully accomplished for the synthesis of unsymmetrical 2,3-, 2,4-, 2,5-, and 2,6-diarylpyridine derivatives. Furthermore, a one-pot synthesis of unsymmetrical diarylpyridines starting from bromo-2-sulfonyloxypyridine was accomplished to demonstrate the practical convenience. Finally, with this method, an antibacterial agent, a topoisomerase inhibitor, and etoricoxib, a nonsteroidal anti-inflammatory drug, were successfully synthesized from the corresponding bromo-2-hydroxypyridines in overall yields of 80, 86, and 49%, respectively.
- Jeon, Young-Kyo,Kim, Seo-Eun,Kim, Won-Suk,Lee, Jae-Yeon
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p. 7399 - 7412
(2020/07/07)
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- METHOD OF PRODUCING UNSYMMETRICAL DISUBSTITUTED PYRIDINE COMPOUNDS
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The present invention relates to a method for producing an asymmetric disubstituted pyridine compound using a position selective Suzuki-Miyaura coupling reaction.
- -
-
Paragraph 0255-0258; 0266-0267
(2021/01/12)
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- Synthetic method and applications of polysubstituted pyridine derivative
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The invention belongs to the field of organic chemical synthesis, and relates to a synthetic method and applications of a polysubstituted pyridine derivative. According to the method, a 2,3-triazine compound and a ketone compound are used as reaction substrates, and can be subjected to a one-step reaction under the action of a catalytic amount of an alkali to synthesize polysubstituted pyridine, wherein the reaction does not involve in the use of danger and controlled drugs, so that a simple, safe, efficient and environment-friendly way is provided for synthesis of polysubstituted pyridine. According to the invention, the reaction can also be used for synthesis of drug molecules, such as one-step synthesis of drug molecule etoricoxib and a derivative thereof; and the product obtained by the invention is further derivatized to obtain multiple types of pyridine functional group-containing active molecules, such as two-step synthesis of active molecules 2-SORA.
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Paragraph 0095-0100
(2020/04/22)
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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
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supporting information
p. 433 - 438
(2020/02/13)
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- 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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- Etoricoxib purification and preparation method
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The invention relates to an etoricoxib purification method which includes the operation: performing reduction reaction on etoricoxib crude drugs to be purified and reduction agents in solvents. The invention further relates to a method for preparing etoricoxib. The purity of the finished etoricoxib prepared by the preparation method is higher than 99.9%, the total content of an impurity F, an impurity 20 and an impurity 21 is lower than 0.001%, and no impurity M is detected.
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Paragraph 0065; 0136-0137; 0140; 0149; 0156; 0163; 0178
(2019/04/17)
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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; 0158-0161
(2019/12/02)
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- Heterocyclic Allylsulfones as Latent Heteroaryl Nucleophiles in Palladium-Catalyzed Cross-Coupling Reactions
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Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant of the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents and, when treated with a Pd(0) catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents.
- Markovic, Tim,Murray, Philip R.D.,Rocke, Benjamin N.,Shavnya, Andre,Blakemore, David C.,Willis, Michael C.
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p. 15916 - 15923
(2018/11/23)
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- Method for preparing etoricoxib
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The invention discloses a method for preparing etoricoxib, and provides a method for preparing etoricoxib I. The method comprises the following step: performing neutralization reaction on hydrohaloride of the etoricoxib I and alkali in a halogenated hydrocarbon solvent to obtain the etoricoxib I, wherein X is halogen. The preparation method is mild in reaction condition, simple and safe in operation and high in yield, no special purification equipment is required, column chromatography separation operation in a posttreatment process is avoided, and the prepared etoricoxib is high in purity (the purity is equal to or higher than 99.5 percent, the content of all impurities is equal to or lower than 0.10 percent, and a raw medicament standard can be met), low in cost and suitable for industrial production.
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Paragraph 0055; 0056; 0057; 0060; 0061; 0064; 0065
(2017/08/02)
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- Preparation technology of etoricoxib and reference substance 5-chloro-3-(4-(methyl sulphonyl)phenyl)-2,3-bipyridine of etoricoxib
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The invention discloses a preparation technology of etoricoxib and a reference substance 5-chloro-3-(4-(methyl sulphonyl)phenyl)-2,3-bipyridine of etoricoxib. The preparation technology comprises steps as follows: 5-chloro-2-hydroxypyridine is taken as a raw material and subjected to a substitution reaction, and 5-chloro-3-iodopyridine-2-ol is obtained; 5-chloro-3-iodopyridine-2-ol is subjected to a coupled reaction, and 5-chloro-3-(4-(methyl sulphonyl)phenyl)pyridine-2-ol is obtained; 5-chloro-3-(4-(methyl sulphonyl)phenyl)pyridine-2-ol is subjected to the substitution reaction, and 2-bromo-5-chloro-3-(4-(methyl sulphonyl)phenyl)pyridine is obtained; 2-bromo-5-chloro-3-(4-(methyl sulphonyl)phenyl)pyridine is subjected to the coupled reaction, a target product etoricoxib or the reference substance 5-chloro-3-(4-(methyl sulphonyl)phenyl)-2,3-bipyridine of etoricoxib is obtained, and the total yield can reach 18%. The route is one novel technology for synthesizing etoricoxib or the reference substance 5-chloro-3-(4-(methyl sulphonyl)phenyl)-2,3-bipyridine of etoricoxib, and the blank of a synthesis method of the reference substance 5-chloro-3-(4-(methyl sulphonyl)phenyl)-2,3-bipyridine of etoricoxib in China is filled up accordingly.
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- A General, One-Pot Method for the Synthesis of Sulfinic Acids from Methyl Sulfones
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A simple and efficient method for converting methyl sulfones to sulfinic acids is described. The process involves alkylation with a benzylic halide, followed by in situ elimination of the resulting styrene in the presence of excess base to yield a sulfinic acid in a single reaction process. The usefulness of the alkylation-elimination sequence is demonstrated by generating a variety of sulfinic acids from methyl sulfones. Late stage functionalization and 14C-labeling of several biologically active methyl sulfones were accessed via sulfinate intermediates.
- Gauthier, Donald R.,Yoshikawa, Naoki
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supporting information
p. 5994 - 5997
(2016/12/09)
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- Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates
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A selection of heteroaryl fluorosulfates were readily synthesized using commercial SO2F2 gas. These substrates are highly efficient coupling partners in the Suzuki reaction. Through judicious selection of Pd catalysts the fluorosulfate functionality is differentiated from bromide and chloride; the order of reactivity being: -Br> -OSO2F> -Cl. Exploiting this trend allowed the stepwise chemoselective synthesis of a number of polysubstituted pyridines, including the drug Etoricoxib. A selection of heteroaryl fluorosulfates were readily synthesized using commercial SO2F2 gas. These substrates are highly efficient coupling partners in the Suzuki reaction. Through judicious selection of Pd catalysts the fluorosulfate functionality is differentiated from bromide and chloride; the order of reactivity being: -Br> -OSO2F> -Cl. Exploiting this trend allowed the stepwise chemoselective synthesis of a number of polysubstituted pyridines, including the drug Etoricoxib.
- Zhang, Enxuan,Tang, Jiaze,Li, Suhua,Wu, Peng,Moses, John E.,Sharpless, K. Barry
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supporting information
p. 5692 - 5697
(2016/04/20)
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- PROCESS FOR MAKING ETORICOXIB
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The invention relates to an improved process and novel intermediates (4) and (6) for the preparation of pharmaceutically active compound etoricoxib of formula (1).
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Page/Page column 10
(2015/03/28)
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- PROCESS FOR MAKING ETORICOXIB
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The invention deals with a novel process, and intermediates for making the pharmaceutically useful product etoricoxib of formula (1), said process inter alia being based on using the compound of formula (4), as reagent and compound (5) as intermediate.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ETORICOXIB AND POLYMORPHS THEREOF
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The invention relates to an improved process for the preparation of etoricoxib and polymorphs thereof. In particular, the, invention relates to a process for the preparation of stable crystalline Form-I of etoricoxib. Further, the invention also relates to a process for the preparation of amorphous form of etoricoxib. The invention also relates to pharmaceutical compositions that include the stable crystalline Form-I of etoricoxib.
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Page/Page column 21
(2013/07/25)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ETORICOXIB
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The present invention relates to an improved process for the preparation of Etoricoxib by reacting ketosulfone of formula-ll with vinamidinium salt of formula-Ill in the presence of an acid, followed by conversion to an acid addition salt and finally desaltifying to get Etoricoxib of formula-l.
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Page/Page column 7
(2013/10/21)
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- PROCESS FOR CYCLOOXYGENASE-2 SELECTIVE INHIBITOR
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The present invention describes a process for preparing a cyclooxygenase-2 selective inhibitor. It provides a synthetic procedure for the said substance namely 5-chloro-3-(4-methylsulphonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine of formula (I). The invention also relates to preparation of a new intermediate of formula (IV) and a process to prepare it. Furthermore, the invention describes a process for preparing another key intermediate of formula (II). Compounds of formula (IV) and formula (II) are useful intermediates in synthesis of the said cyclooxygenase-2 inhibitor.
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- PROCESS FOR THE SYNTHESIS OF ETORICOXIB
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The present invention relates to a process for the synthesis of the anti-inflammatory agent 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridine, referred to as compound of formula (1) or etoricoxib, which is a pharmaceutically active ingredient inhibiting cyclooxygenase-2. In particular, the application concerns a novel process of making the compound of formula (1) by oxidizing a compound of formula (4).
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Page/Page column 21
(2013/07/25)
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- A PROCESS FOR CYCLOOXYGENASE-2 SELECTIVE INHIBITOR
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The present invention describes a process for preparing a cyclooxygenase-2 selective inhibitor. It provides a synthetic procedure for the said substance namely 5-chloro-3-(4-methylsulphonyl) phenyl-2-(2-methyl-5-pyridinyl) pyridine of formula (I). The invention also relates to preparation of a new intermediate of formula (IV) and a process to prepare it. Furthermore, the invention describes a process for preparing another key intermediate of formula (II). Compounds of formula (IV) and formula (II) are useful intermediates in synthesis of the said cyclooxygenase-2 inhibitor.
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Page/Page column 20
(2012/06/01)
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- SOLID STATE FORMS OF ETORICOXIB SALTS
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Provided herein are novel solid state forms of etoricoxib salts, process for their preparation, pharmaceutical compositions, and method of treating thereof. The etoricoxib salts include an oxalate salt, a succinate salt, a fumarate salt, a besylate salt, a hydrobromide salt, a glutamate salt, a sulfamate salt, a benzoate salt, a cinnamate salt, a salicylate salt, or a tosylate salt. The solid state forms of etoricoxib salts disclosed herein are useful for preparing etoricoxib free base with high purity.
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Page/Page column 28
(2012/02/01)
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- A PROCESS FOR THE PREPARATION OF ETORICOXIB
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The present invention provides a improved process for preparing Etoricoxib using substituted β-chlorovinaniidinium salts containing a cyclic group, optionally containing a heteroatom. The present invention also provides a process for the preparation of the intermediate β-chlorovinamidinium salts. In one of the embodiments is provided a process for the purification of Etoricoxib as well as the intermediates.
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Page/Page column 16
(2010/09/17)
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- Phosphorodiamidate-directed metalation of N -heterocycles using Mg- and Zn-TMP bases
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Figure presented The strong directing ability of the N,N,N′,N′- tetramethyldiaminophosphorodiamidate group has been used to achieve selective metalations on various heterocycles such as pyridines, quinolines and quinoxalines with TMP-derived bases like TMPMgCl·LiCl, TMP 2Mg·2LiCl, and TMP2Zn·2MgCl 2·2LiCl. This protocol was applied in the synthesis of etoricoxib, talnetant and a P-selectin inhibitor.
- Rohbogner, Christoph J.,Wirth, Stefan,Knochel, Paul
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scheme or table
p. 1984 - 1987
(2010/07/15)
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- 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3]bipyridinyl in pure crystalline form and process for synthesis
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This invention encompasses a pharmaceutical composition comprising the compound of formula A: in combination with a pharmaceutically acceptable carrier, said compound being comprised of about 1-50%, 1-20% or 1-10% of the polymorphic form which is designated Form V and the remainder of the compound being comprised of at least one polymorphic form selected from the group consisting of: Form I, Form II, Form III and Form IV.
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- Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
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This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a combination comprising an NSAID, or a pharmaceutically acceptable salt thereof, and an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-1 or cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.
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- Combination of an allosteric alkyne inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
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The invention provides a combination, comprising an allosteric alkyne inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric alkyne inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric alkyne inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a combination comprising an NSAID, or a pharmaceutically acceptable salt thereof, and an allosteric alkyne inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric alkyne inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-1 or cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric alkyne inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.
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- Combination of an allosteric inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
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This invention provides a combination, comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, and a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, and a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib, and a pharmaceutically acceptable carrier, diluent, or excipient. The invention further provides a combination, comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.
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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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- Combinations of an alpha-2-delta ligand with a selective inhibitor of cyclooxygenase-2
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The invention relates to a combination, comprising a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, and an Alpha-2-delta ligand, or a pharmaceutically acceptable salt thereof, and valdecoxib. Examples of selective inhibitors of COX-2 include valdecoxib, rofecoxib, and celecoxib. Examples of Alpha-2-delta ligands include gabapentin, pregabalin, (3S,4S)-(1-Aminomethyl-3,4-dimethyl-cyclopentyl)-acetic acid, and 3-(1-aminomethyl-cyclohexylmethyl)-4H-[1,2,4]oxadiazol-5-one hydrochloride. The combinations are useful for treating certain diseases including cartilage damage, inflammation, pain, and arthritis.
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- 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3']bipyridinyl in pure crystalline form and process for synthesis
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This invention encompasses the Form V polymorph of Compound A of structural formula: 1which is useful in the treatment of cyclooxygenase-2 mediated diseases. The invention encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising the Form V polymorph of Compound A. The invention also encompasses a process for synthesizing the Form V polymorph of Compound A.
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- 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3]bipyridinyl in pure crystalline form and process for synthesis
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This invention encompasses a pharmaceutical composition comprising the compound of formula A: in combination with a pharmaceutically acceptable carrier, said compound being comprised of about 1-50%, 1-20% or 1-10% of the polymorphic form which is designated Form V and the remainder of the compound being comprised of at least one polymorphic form selected from the group consisting of: Form I, Form II, Form III and Form IV
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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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- Process for making diaryl pyridines 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 cyclooxygenase-2 mediated diseases.
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Page column 12
(2010/01/31)
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- Combination therapy for reducing the risks associated with cardio-and-cerebrovascular disease
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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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- A practical synthesis of a COX-2-specific inhibitor
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A number of synthetic strategies to the Cox-2 specific inhibitor 1 have been described. These studies have led to the identification of a novel pyridine construction using annulation of ketone 2 using a vinamidinium species 29 and ammonia in 97% assay yield. Three approaches to the synthesis of ketone 2 are described that allow for its preparation in large quantities in >65% overall yield from methyl 6-methylnicotinate.
- Davies,Marcoux,Corley,Journet,Cai,Palucki,Wu,Larsen,Rossen,Pye,DiMichele,Dormer,Reider
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p. 8415 - 8420
(2007/10/03)
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- Substituted pyridines as selective cyclooxygenase-2 inhibitors
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The invention encompasses the novel compound of Formula I as well as a method of treating COX-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 COX-2 mediated diseases comprising compounds of Formula I.
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- 2-pyridinyl-3(4-methylsulfonyl)phenylpyridines: Selective and orally active cyclooxygenase-2 inhibitors
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A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5- Chloro-3-(4-methylsulfonyl)phenyl-2(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.
- Friesen, Richard W.,Brideau, Christine,Chan, Chi Chung,Charleson, Stella,Deschenes, Denis,Dube, Daniel,Ethier, Diane,Fortin, Rejean,Gauthier, Jacques Yves,Girard, Yves,Gordon, Robert,Greig, Gillian M.,Riendeau, Denis,Savoie, Chantai,Wang, Zhaoyin,Wong, Elizabeth,Visco, Denise,Xu, Li Jing,Young, Robert N.
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p. 2777 - 2782
(2007/10/03)
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