- Anti-inflammatory, antiproliferative, and radical-scavenging activities of tolfenamic acid and its metal complexes
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Some new complexes of tolfenamic acid (=2-[(2-methyl-3-chlorophenyl)amino] benzoic acid; Htolf) with potentially interesting biological activities are described. The complexes [Mn(tolf)2(H2O)2], [Co(tolf)2(H2O)2], [Ni(tolf2(H 2O)2], [Cu(tolf)2(H2O)]2 , and [Zn(tolf)2(H2O)] were prepared by the reaction of tolfenamic acid, a potent anti-inflammatory drug, with metal salts. The radical-scavenging activities of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay. Their ability to inhibit soybean lipoxygenase, β-glucuronidase, and trypsin-induced proteolysis was studied. Their inhibitory effects on rat paw edema induced by carrageenin was studied and compared with those of tolfenamic acid. The complex [Zn(tolf)2(H2O)] exhibited the strongest in vivo inhibitory effect at 0.1 mm/kg Body Weight (BW; 93.0±0.9%), superior than the inhibition induced by tolfenamic acid at the same molar dose (76.0±0.9%). Tolfenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), and A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The complexes [Mn(tolf)2(H2O)2] and [Cu-(tolf)2(H2O)]2 have shown selectivity against T24 cell line. The IC50 values of these two complexes against T24 cancer cell lines are in a micromolar range similar or better to that of the antitumor drug cisplatin.
- Kovala-Demertzi, Dimitra,Hadjipavlou-Litin, Dimitra,Primikiri, Alexandra,Staninska, Malgorzata,Kotoglou, Chronis,Demertzis, Mavroudis A.
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Read Online
- 2-arylamine compound and preparation method and application thereof
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The invention discloses a 2-arylamine compound and a preparation method and application thereof. The structure of the 2-arylamine compound is as shown in a formula I shown in the specification, wherein in the formula, the definition of each substituent group is as described in the specification and claims. The compound provided by the invention has a good inhibition effect on fatty acid binding protein 4, and can be used for prevention, treatment or adjuvant treatment of metabolic diseases, inflammations and cancers related to activity or expression of FABP4.
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Paragraph 0108-0111; 0162-0165
(2021/05/05)
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- Water-phase synthesis method of tolfenamic acid
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The invention discloses a water-phase synthesis method of tolfenamic acid. The method comprises the following steps: adding o-halobenzoic acid and inorganic base into water, and performing heating to dissolve; adding 3-chloro-2-methylaniline, cuprous iodide and alkali metal iodide into the mixed solution obtained in the previous step, and conducting heating for reaction; performing cooling, then adding ethyl acetate for extraction and liquid separation, acidifying and crystallizing a water phase with hydrochloric acid, performing filtering, taking a filter cake as a crude tolfenamic acid product, and recrystallizing the crude tolfenamic acid product to obtain a refined tolfenamic acid product. The preparation method has the advantages of simple operation steps, wide applicability of starting materials, use of water as a reaction solvent, greenness, environmental protection, high yield, reduction of the preparation cost, and suitableness for industrial production, and finally a high purity tolfenamic acid product can be obtained.
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Paragraph 0029; 0030
(2021/04/10)
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- Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3
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The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of “scissors” cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC50 values on each tested cell line ranging from 7.37 to 18.62 μM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.
- Ma, Shumeng,Zhu, Longqing,Fan, Xiaohong,Luo, Tian,Liu, Dan,Liang, Ziyi,Hu, Xiaoling,Shi, Tao,Tan, Wen,Wang, Zhen
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- OXOACRIDINYL ACETIC ACID DERIVATIVES AND METHODS OF USE
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Compounds of Formula I or pharmaceutically acceptable salts or esters thereof capable of binding to and modulating the activity of a stimulator of interferon genes (STING) protein are provided. Methods involving compounds of Formula I as effective modulators of STING are also provided.
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Page/Page column 199
(2019/06/05)
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- Intermolecular Reductive C-N Cross Coupling of Nitroarenes and Boronic Acids by PIII/PV=O Catalysis
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A main group-catalyzed method for the synthesis of aryl- and heteroarylamines by intermolecular C-N coupling is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane) and a terminal hydrosilane reductant (phenylsilane) to drive reductive intermolecular coupling of nitro(hetero)arenes with boronic acids. Applications to the construction of both Csp2-N (from arylboronic acids) and Csp3-N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3-N bond formation. The method constitutes a new route from readily available building blocks to valuable nitrogen-containing products with complementarity in both scope and chemoselectivity to existing catalytic C-N coupling methods.
- Nykaza, Trevor V.,Cooper, Julian C.,Li, Gen,Mahieu, Nolwenn,Ramirez, Antonio,Luzung, Michael R.,Radosevich, Alexander T.
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supporting information
p. 15200 - 15205
(2018/11/30)
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- A method for synthesis of tolfenamic acid
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The invention discloses a method for synthesizing tolfenamic acid. The method includes the following steps: adding o-chlorobenzoic acid and alkali metal hydroxide into methyl isobutyl ketone to obtain a mixture, and then heating up and enabling the mixture to react; adding 3-chloro-2-methylaniline and an alumina supported inorganic base acid-binding agent into the reacted mixture obtained in the previous step, and then heating up and enabling the mixture to react; cooling, adding water to extract, skimming, acidizing and crystallizing an aqueous phase using hydrochloric acid, filtering to obtain filter cakes which are tolfenamic acid crude products, and then recrystallizing the crude products to obtain tolfenamic acid refined products. According to the invention, the alumina supported inorganic base can be used not only as the acid-binding agent but also as a catalyst of the reaction, thereby improving the cleanness of industrial synthetic reactions and reducing environmental pollution.
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Paragraph 0016; 0017; 0018
(2016/12/22)
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- Prodrugs of non-steroidal anti-inflammatory and carboxylic acid containing compounds
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Compounds of the formula: RC(O)O-spacer-OC(O)R′, wherein (i) RC(O)— is the acyl residue of an NSAID or other pharmaceutically active agent bearing a carboxylic acid function, (ii) spacer is Cn alkyl, (iii) n is from 1 to 6, and (iv) R′ is substituted or unsubstituted heteroaryl or heterocycle, and pharmaceutical compositions thereof.
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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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- Prodrug derivatives of carboxylic acid drugs
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Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
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- Structure-activity relationships in a series of anti-inflammatory N-arylanthranilic acids
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A large series of N-arylanthranilic acids has been prepared. Many of these compounds show high anti-inflammatory activity as measured by the anti-UV-erythema test. From this series have come the clinically useful nonsteroidal anti-inflammatory agents, flufenamic acid (Arlef), mefenamic acid (Ponstel), and the latest and most potent agent, N-(2,6-dichloro-m-tolyl)anthranilic acid (meclofenamic acid, Meclomen = the sodium salt). The structure-activity relationships of this series is discussed and a graphical representation is presented which allows the prediction of activity of new agents.
- Kaltenbronn,Scherrer,Short,Jones,Beatty,Saka,Winder,Wax,Williamson
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p. 621 - 627
(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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- Antiphlogistic phenylacetohydroxamic acid compositions
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Phenylacetohydroxamic acids having the formula I STR1 wherein R1, R2, R3 and R4, independently of each other, represent hydrogen, chlorine, fluorine or bromine atoms or an alkyl or alkoxy group having at most 6 carbon atoms, and wherein R2 may additionally represent a trifluoromethyl group with the proviso that R1, R2 and R3 may not simultaneously represent hydrogen atoms and their pharmaceutically acceptable salts with bases, which compounds inhibit plateletaggregation and exhibit valuable pharmacological, in particular, antiphlogistic, analgesic and antipyretic activity.
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