Arylamine n-(3'-harbutt-2'-yl)anthranilic acid, exhibiting anti-inflammatory activity

 

(57) Abstract:

The invention relates to new biologically active arylamides N-(3'-harbutt-2'-yl)Anthranilic acid of formula (1), where R is 2-CH3, 3-CH3that have anti-inflammatory activity and due to this can be used as the basis of new drugs. 1 PL.

The claimed compounds are organic chemistry, to the class of aromatic amino acids, namely new biologically active arylamides N-(3'-harbutt-2'-yl)Anthranilic acid, which can be used as the basis of new drugs, the following formula:

< / BR>
where R is 2-CH3(1), 3-CH3(2)

The closest structural analogue of the claimed compounds is 4-bromanil N-allyl-N-adamantyl-1')Anthranilic acid, exhibiting anti-inflammatory and analgesic activity [patent RU 2030394 on the invention: "4-bromanil N-allyl-N-(adamantyl-1')Anthranilic acid, exhibiting anti-inflammatory and analgesic activity"].

< / BR>
In medical practice used anti-inflammatory agent ortofen [Mashkovsky M. D. Medicines (manual FA/P> The aim of the invention is to obtain new arylamido N-(3'-harbutt-2'-yl)Anthranilic acid (1 and 2), which has anti-inflammatory action.

This goal is achieved by the synthesis of arylamines N-(3'-harbutt-2'-yl)Anthranilic acid-based methyl ester of N-(3'-harbutt-2'-yl)Anthranilic acid, which was used in magnesiumalloy reactions:

< / BR>
< / BR>
where R is 2-CH3(1), 3-CH3(2).

An example of obtaining orthotoluidine N-(3-harbutt-2-yl)Anthranilic acid (1).

To EtMgBr obtained from 16.3 g (0.15 mol) EtBr, 3.6 g (0.15 mol) of Mg in 30 ml of absolute ether, poured 7.0 g (0,075 mol) of ortotoluidine in 20 ml of absolute ether is heated on a water bath for 30 min, then poured dropwise a solution of 12.0 g (0.05 mol) of methyl ester of N-(3'-harbutt-2'-yl)Anthranilic acid and 20 ml of absolute ether, again heated for 30 minutes After completion of the reaction magyarkanizsa connection decompose 10% SN3COOH. The ether layer is separated and the aqueous extracted with CH ml of ether. Essential extracts the solvent is distilled off with steam. The crystals So pl. 110-112oC. Yield 68%. Found, %: N 8,60; C1 11,00; calculated, %: N 8,89; Cl of 11.26. The IR spectrummaxcm-1: 3360, 3200 (NH), 1630 (C=O), 1580, 1520, 1470 (AG). P is of metatoluidine N-(3-harbutt-2-yl)Anthranilic acid (2).

To EtMgBr obtained from 16.3 g (0.15 mol) EtBr, 3.6 g (0.15 mol) of Mg in 30 ml of absolute ether, poured 7.0 g (0,075 mol) Metato-Luigina in 20 ml of absolute ether is heated on a water bath for 30 min, then poured dropwise a solution of 12.0 g (0.05 mol) of methyl ester of N-(3'-harbutt-2'-yl)Anthranilic acid and 15 ml of absolute ether and again heated for 30 minutes After completion of the reaction magyarkanizsa connection decompose 10% CH3COOH. The ether layer is separated and the aqueous extracted with CH ml of ether. Essential extracts the solvent is distilled off with steam. The crystals So pl. 94-96oC. The Yield Of 52%. Found, %: N 8,64; Cl 11,50; calculated, %: N 8,89; C1 of 11.26. The IR spectrummaxcm-1: 3230 (NH), 1680 (C=O), 1640, 1590, 1500 (AG). PMR-spectrum, DMSO, , M. D.: 2,1 d (6N, CH3); 3,86 d (2H, CH2); 5,43 m (N, CH); 6,33-7,46 m (8H, Ah); 7,66 (H,NH).

The claimed compounds are crystalline substances with a yellowish tinge, insoluble in water, soluble in dimethylformamide and dimethylsulfoxide.

Study of acute toxicity and anti-inflammatory activity was performed at the Department of pharmacology pharmaceutical Academy, Perm. Was determined acute toxicity (LD50connections on white mice weighing 16-20 grams in a single unwel animals were recorded within 1 day. LD50figured Express-method at P=0.05 [Prozorovsky Century B. a Practical guide for rapid determination of the average effective doses and concentrations of biologically active substances. S.-Petersburg: SPE-Science, 1992].

Anti-inflammatory effect of the compounds studied in accordance with the methodological guidelines for experimental study of non-steroidal anti-inflammatory pharmacological substances, approved by the pharmacological Committee of the USSR Ministry of health (Protocol 22 of 11.11.82). Experiments carried out on outbred white rats weighing 150-220 g on the model of acute inflammatory edema caused subplanetary introduction in the rear paw of the rat 0.1 ml of 1% solution carragenin. On anti-inflammatory activity was assessed by inhibition of edema of the foot in relation to the control. The volume of the foot was measured ecometrics [Salamon R. S. Medicinal regulation of the inflammatory process. L., 1958. - S. 11-43]. As the comparison drug used ortofen. The compounds (50 mg/kg) and ortofen (10 mg/kg) was administered intraperitoneally 1 hour before the introduction of carragenine. Evaluation of anti-inflammatory action was performed at 4 h after injection phlogogenic agent. The results of the experiments are processed statistically with the calculation criteria the claimed compounds are completely harmless (LD50match >4000 mg/kg) compounds have 54 times less toxicity in comparison with ortofen and 1.6 times in comparison with similar structure. Antiinflammatory activity of the claimed compounds (50 mg/kg) is equal to ortofen (10 mg/kg) and a structural analogue. Conditional latitude pharmacological action (USFD) the claimed compounds 10.8 times more USFD ortofena and 1.6 times of similar structure.

The claimed compounds are promising as agents exhibiting anti-inflammatory effect, similar in activity to a similar structure and pattern comparison action - ortofen, but have the advantages of toxicity and USFD in comparison with them.

Thus, the proposed compounds may find application in medicine as the basis for the creation of new anti-inflammatory drugs.

Arylamine N-(3'-harbutt-2'-yl)Anthranilic acid formula

< / BR>
where R is 2-CH3(1), 3-CH3(2)

exhibiting anti-inflammatory activity.

 

Same patents:

The invention relates to a new connection is anilide N-(3'-harbutt-2'-yl)Anthranilic acid, exhibiting anti-inflammatory and analgesic activity

-diethylaminopropylamine acid with its application" target="_blank">

The invention relates to the production of biologically active chemical compounds and can be used in the production of locally-anestesiologi tools Amylocaine - hydrochloride octabrominated-diethylaminopropylamine acid

The invention relates to preparations of nimesulide for local use based gel systems

The invention relates to new derivatives of 2-renominate General formula (I), where R1and R2represent hydrogen, C1-C6-alkyl, deformity, trifluoromethyl, C3-C6-cycloalkyl, saturated 5-membered heterocycle containing one oxygen atom, indanyl, 6,7-dihydro-5H-cyclopentadienyl or1-C6-alkyl, substituted phenyl, indayla or3-C6-cycloalkyl, R3is hydrogen, R4represents hydrogen, halogen, C1-C6-alkyl, trifluoromethyl, or R4represents a radical of the formula-O-R7where R7is hydrogen, R5represents hydrogen or R4and R5taken together may form a bivalent radical of formula-CH2-CH2-O-CH2-CH2-, R6represents hydrogen or C1-C6-alkyl, -a-b - represents a bivalent radical of the formula- (CR10= CR11or СНR10-СНR11where each R10and R11independently represents hydrogen or C1-C6-alkyl, L represents hydrogen, C1-C6-alkyl, C1-C6-allyloxycarbonyl,1-C6-alkyl, substituted by one or two penilai

The invention relates to solutions for surgical irrigation and methods of use thereof, in particular to anti-inflammatory, analgesic and anticonvulsant solutions

The invention relates to medicine and to the use of at least one peptide containing the C-end of the Tripeptide Lysine-Proline-Valine, in which a Proline residue is in the form of programalso optical isomer for the local treatment of inflammation
The invention relates to pharmaceutical industry and veterinary

The invention relates to cosmetology

The invention relates to the processing of larch wood with getting bioflavonoids, specifically dihydroquercetin (DQC), which finds application in medicine, food industry

The invention relates to new phenanthridine derivative of the General formula I and II and their salts, where R1represents an aromatic carbocyclic residue, which is derived from benzene or naphthalene, or represents a heterocyclic residue, which is derived from furan, thiophene or pyridine, and R1may have one or more substituents, and these substituents selected from monoamino, alkylamino, dialkylamino-, alkyl-, alkoxy-, alkylene and galactography, a R2and R3that may be the same or raznie, represent a hydrogen atom, CNS residue, accelerometry residue, a halogen atom or a nitro-group

The invention relates to medicine and can be used to treat a variety of rhinitis: allergic, polynosic, year-round

The invention relates to pharmaceutical industry
The invention relates to the neurotropic agent, representing the (RS)-N-pantoyl-aminobutyric acid or its pharmaceutically acceptable salt: sodium, potassium, calcium, magnesium or zinc, as well as two means of obtaining it, which is or condensing RS-pantolactone salt-aminobutyric acid in alcohol followed by treatment of the salts with organic or mineral acid or a cation exchange resin in the H+form; or in condensing RS-pantolactone salt-aminobutyric acid in alcohol followed by treatment received calcium or magnesium salt of an inorganic salt or cation exchange resin in the corresponding salt form

The invention relates to medicine, and is intended for the prevention of delayed emesis

The invention relates to medicine, and is intended for the prevention of delayed emesis

The invention relates to the derivatives of colchicine formula (I), where R denotes methoxy or methylthiourea; R1means a linear or branched C1- C6alkyl, provided that when R is methoxy, R1cannot be methyl; and compounds of formula II, where R is methylthio; R1means a linear or branched C1- C6-alkyl

The invention relates to new derivatives of phenoxyethylamine General formula (I) where the substituents have the values with high affinity to 5-HT1Areceptor

The invention relates to medicine, particularly cardiology, and for the prevention of a second heart attack in individuals without hypertension

The invention relates to a new connection is anilide N-(3'-harbutt-2'-yl)Anthranilic acid, exhibiting anti-inflammatory and analgesic activity

The invention relates to a new compound - amide N-allylestrenol acid, exhibiting anti-inflammatory, analgesic and antihypoxic activity
Up!