- Polymorphism in the Anti-inflammatory Drug Flunixin and Its Relationship with Clonixin
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Crystallization of the nonsteroidal anti-inflammatory drug (NSAID) flunixin in acetone and in acetone-hexane produced two conformational polymorphs, as predicted by hydrogen-bond propensity analyses, which are similar to three of the polymorphs of the rel
- Camargo, Hernando A.,Contreras, Jines E.,Dávila-Miliani, María Cecilia,Díaz De Delgado, Graciela,Delgado, José Miguel,Dugarte-Dugarte, Analio,Henao, José Antonio,Toro, Robert A.
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- An investigation of the polymorphism of a potent nonsteroidal anti-inflammatory drug flunixin
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Flunixin [2-(3-trifluoromethyl-2-methyl-phenylamino)-nicotinic acid, FLX], a potent nonsteroidal anti-inflammatory drug widely used in veterinary medicine, was found to exist in at least two crystal forms (I and II), in contrast to clonixin [2-(3-chloro-2-methyl-phenylamino)-nicotinic acid, CLX], which exists in four solvent-free forms and multiple solvates. Form I was harvested from a variety of solvents and characterized by single-crystal X-ray diffraction, PXRD, FT-IR, and Raman spectroscopy. Its crystal structure is sustained on the strong acid-pyridine hydrogen bond. Form II was generated by thermal treatment of form I. Other aspects of this polymorphic system were investigated both experimentally and theoretically. Quantum chemistry calculations were performed to shed light on the lack of polymorphism from solution-phase crystallization. Conformational scan of the dihedral angle C2-N7-C8-C9 (τ) revealed two stable conformations, one with τ near 170°, and the other near 70°, corresponding to the molecule in the crystal. Hirshfeld analysis accounted for the major intermolecular interactions contributing to the overall stability of the crystal.
- Liu, Hao,Yang, Xing,Wu, Shanyu,Zhang, Mingtao,Parkin, Sean,Cao, Shuang,Li, Tonglei,Yu, Faquan,Long, Sihui
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- Preparation method of flunixin meglumine
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The invention discloses a preparation method of flunixin meglumine the preparation method, and the method specifically comprises the following steps: (1) adding 2-chloronicotinic acid and 2-methyl-3-trifluoromethyl aniline into a sodium hydroxide water solution for stirring, adding ethylene glycol as well as a phase transfer catalyst and p-toluenesulfonic acid and copper oxide, controlling the temperature and time, adjusting the pH value of the solution, stirring, standing, layering, stirring, filtering, washing filter cake, and drying to obtain flunixin; and (2) reacting the flunixin obtainedin the step (1) with N-methylglucosamine in isopropyl alcohol, and meanwhile, adding a filler; carrying out heating reflux, filtering, cooling, stirring and crystallizing, carrying out crystal suction filtration, and washing crystals with isopropanol to obtain the flunixin meglumine. The preparation method of the flunixin meglumine is convenient and simple in operation, the reflecting efficiencyis high, the reaction temperature is low, the reaction time is short, and the cost is low; moreover, the prepared flunixin meglumine is high in purity and high in yield.
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Paragraph 0022-0024; 0026-0037; 0042-0045; 0054-0057
(2019/01/24)
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- A synthesis method of synthesis and (by machine translation)
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The invention belongs to the technical field of chemical synthesis, in particular relates to a synthesis method of synthesis and. The method comprises the following steps: 2 - chloro nicotinic acid and 2 - methyl - 3 - trifluoromethyl aniline in the perfluoro sulfonic acid resin under the catalysis of the reaction to produce synthesis and. The method adopts the perfluoro sulfonic acid resin as catalyst, fast response, high yield, the yield of this step can be up to 97%. (by machine translation)
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Paragraph 0025; 0026; 0027; 0028
(2018/10/11)
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- Process for preparing flunixin and intermediates thereof
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Process for preparing a key intermediate, 2-methyl-3-trifluoromethylaniline (MTA) of Flunixin, as well as novel intermediates thereof are described.
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- Methods for use of GABAa receptor GABAergic compounds
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A method is disclosed for potentiating mammalian GABA A receptor responses to GABA. The receptor responses are potentiated according to the invention by contacting GABA A receptors with GABA and an effective amount of non-steroidal anti-inflammatory agents, in particular, fenamates and structurally related compounds.
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- Process for preparing Flunixin and intermediates thereof
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Process for preparing a key intermediate, 2-methyl-3-trifluoromethylaniline (MTA) of Flunixin, as well as novel intermediates thereof are described.
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- Improved Process for the Preparation of 2-Methyl-3-trifluoromethylaniline: A Versatile Intermediate for Flunixin Synthesis
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A detailed new experimental investigation into the synthesis of Flunixin via 2-methyl-3-trifluoromethylaniline is described.The coupling process between 2-methyl-3-trifluoromethylaniline and 2-chloronicotinate was achieved stoichiometrically and in high yield, when ethylene glycol was used as reaction solvent at 160 deg C.
- Jaouhari, Rabih,Quinn, Philip
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p. 2243 - 2246
(2007/10/02)
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- Esters and amides containing the 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetyl moiety
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Compounds of the formula STR1 wherein each X, which may be identical or different from the other X, is oxygen or imino; R1 is hydrogen, fluorine, chlorine or bromine; R2 and R3, which may be identical or different from each other, are each hydrogen; unsubstituted or mono-substituted alkyl of 1 to 6 carbon atoms, where the substituent is phenyl or dialkylamino with 1 to 3 carbon atoms in each alkyl moiety; pyridyl; or cycloalkyl of 5 to 7 carbon atoms; R2 and R3, together with each other and the nitrogen atoms to which they are attached, are pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-aryl-piperazino or N-(alkyl of 1 to 3 carbon atoms)-piperazino; A is cycloalkylene of 5 to 7 carbon atoms; unsubstituted or substituted alkylene of 2 to 10 carbon atoms, where the substituents are one to two alkyls of 1 to 3 carbon atoms each, one to two carbalkoxys of 2 to 4 carbon atoms each, one to two phenyls, one to four hydroxyls, one halomethyl, one hydroxymethyl, one alkanoyloxy of 1 to 18 carbon atoms, one alkanoyloxymethyl of 1 to 18 carbon atoms in the alkanoyl moiety or one STR2 where R1, R2 and R3 have the meanings previously defined; or alkylene of 2 to 10 carbon atoms interrupted by oxygen, sulfur, sulfoxide, sulfonyl, phenyl, cyclohexyl, pyridyl, piperazino or unsubstituted or substituted imino, where the substituent on the imino group is alkyl of 1 to 6 carbon atoms, phenyl or phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety; B is the acyl residue of an antiphlogistic carboxylic acid; and their non-toxic, pharmacologically acceptable acid addition salts. The compounds as well as their salts are useful as anti-inflammatories.
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- Anti-diarrheal anilino nicotinic acids and method of using same
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This invention relates to compositions of matter useful as anti-diarrheal agents and to the method of controlling and treating diarrhea in warm blooded animals. The active anti-diarrheal agents are substituted anilino nicotinic acids, and salts thereof and ester and hydrazine derivatives of said acids.
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