Derivatives of carboxylic acids, inhibitors of metastasis and agents enhancing chemotherapeutic activity of antitumor preparations, method for enhancing effectiveness of cytostatics, method for inhibition of metastasizing process

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to using dicarboxylic acids of the general formula (2): R-CONH-OH (2) wherein R means -HO-HNCO, -HO-NHCOCH-(OH)CH(OH), -HOOC-CH2CH2, -HO-OCCH=CH as inhibitors of metastasis and agents enhancing chemotherapeutic activity of antitumor preparations. Also, invention relates to a method for enhancing effectiveness of cytostatics in carrying out cytostatic chemotherapy of tumors. Method is carried out by using cytostatics in combination with derivatives of dicarboxylic acids of the formula (2). Also, invention relates to a method for inhibition of metastasizing process. Method is carried out by effect of the known cytostatics and derivatives of dicarboxylic acid of the formula (2) on tumor. Proposed substances provide enhancing antitumor and anti-metastatic activity of known cytostatics based on using derivatives of dicarboxylic acids.

EFFECT: valuable medicinal properties of agents and preparations, enhanced effectiveness of metastasizing inhibition.

4 cl, 4 dwg, 7 ex

 

The invention relates to derivatives of dicarboxylic acids, which are physiologically active substances and can be used in medical practice as a low-toxic means to enhance the antitumor and antimetastatic activity of known drugs in cytotoxic cancer chemotherapy. Specifically, the present invention relates to mono - and diacetamide dicarboxylic acids of General formula 2

where R=HONHCO; HONHCOCH(OH)CH(OH); NOESN2CH2NOESN=CH.

The compounds of formula 2 are physiologically active substances and can be used as a means of enhancing antitumor and antimetastatic effects of cytostatics. In addition, these compounds do not cause unlike xenobiotics development of complex reactions to neutralize them using significant energy cells [Saprin A.N. The enzymes of the metabolism and detoxification of xenobiotics. The success biochimie, 1991, 32 S. 146-175].

It is known that cisplatin and cyclophosphamide are used alone or in combination with other drugs or medicines in the treatment of cancer [cancer chemotherapy. Edited Nieremontowany. The Handbook. M.: Medicine, 1986; Npomogaeva, Savonarola, Lampolla, Tasevska, Lterminal and Amorales. The donor of nitric oxide improves the efficiency of cytostatic therapy and delays the development of drug resistance, 2003, v.49, No.1, p.71-75]. However, as a rule, in chemotherapy of leukemia and some other cancers for the positive effects are maximally tolerated doses of cytostatics, and therefore they have very high toxicity towards warm-blooded animals.

The present invention is the development of previously unknown derivatives of dicarboxylic acids that have low toxicity towards warm-blooded animals and allowing in minimum doses and in combination with minimal doses of known drugs to achieve significant therapeutic effects in combination therapy of leukemias and inhibition of metastasis.

The new compounds of formula 2 was synthesized by a known method by processing alilovic esters of carboxylic acids with hydroxylamine (Ber. 1953, Bd 86, s.1186).

The invention is characterized by the following examples.

Example 1. Dihydrexidine (+) tartaric acid. To 45 ml odnopolyarnogo solution of hydroxylamine in the abs. methanol was added dropwise under stirring at room temperature the solution 2,69 g (0,015 mol) dimethyl ether (+) tartaric acid in 10 ml of abs. meth is Nola, and then left at room temperature for 2-3 days. Then was filtered white crystalline precipitate was dried. Received of 1.33 g (73.8%) of dihydrexidine (+) tartaric acid, TPL 170-171°C. an NMR Spectrum1N ((DMSO-d6that δ, ppm, J, Hz), 4.22 (D. CH); 5.33 (d, HE alcohol); 8.75 (USS, NH); 10.38 (Usc, HE COOH). Found (%): 26.18; N, 4.16; N 15.25. C4H8N2O6. Calculated (%): 26.6; N, 4.44; N, 15.6.

Example 2. Monooxime maleic acid (FB-13). The reaction was carried out analogously to example 1. After normal processing of the received monooxime maleic acid with a yield of 74%, TPL 119-120°C. Found(%): 36,50; N 3,88; N 10,41. With4H5NO4. Calculated: 36,64; N 3,82; N 10,69. NMR spectrum1N ((DMSO-d6, 5, ppm,); 10.0 (USS, 3H, COOH, NHOH); 6.25 (USD 2H, CH=CH).

Example 3. Monooxime aspartic acid (FB-14). The reaction was carried out analogously to example 1. 15 ml odnopolyarnogo solution of hydroxylamine and 0.0075 M methyl ester of aspartic acid after normal processing of the received monooxime aspartic acid as a white crystalline substance, with a yield of 69.5%, TPL 142-143°C, C4H8N2O4. Found(%): 32,42; N 5,6; N 19,00 Calculated: 32,43; N. Of 5.40; N 18,92. An NMR spectrum1N ((DMSO-d6that δ, ppm), 8.35 (USS, 5H, COOH, NH2, NH, OH), 3.96 (m, 1H, CH), 271 (m, 2H, CH2).

Example 4. Monooxime succinic acid. The reaction is s carried out analogously to example 1. After normal processing of the received monooxime succinic acid as a white colorless substance with a yield of 70.2%After conventional treatment and drying the substance has TPL 116-118°C. the Yield 64%). An NMR spectrum1N ((DMSO-d6that δ, ppm): 12.1 (such, 1H, HE): 10.4 (such, 1H, COOH); 8.73 (SUS. 1H, NH); 2.42 (T, 2H, CH2); 2.20 (t, 2H, CH2With=0). Found (%): 35.94; H 5.08; N, 7.89. C4H7NO4.. Calculated (%): at 36.09; H 5.26; N, 10.5.

Experimental study of the antitumor activity of the drug FB-13 as chemoembolization was performed on tumor models leukemia R and metastatic carcinoma, Lewis lung, as seen in examples 5 and 6.

Example 5. Leukemia PAL mice-hybrids BDF1intraperitoneally. Inoculum was 106the leukaemic cells in 0.2 ml of saline.

It was investigated the joint effect of the drug FB-13 and cisplatin. The drug was administered in the dose of 10 mg/kg cisplatin 2 mg/kg at 1, 3, 5 and 7 days after transplantation. As the evaluation criterion used is the number cured (lived 60 days) animals. With the introduction of one of cisplatin, this indicator amounted to 66.7%in the joint introduction of cisplatin and FB-13 - 100% of the animals survived.

Example 6. The Lewis lung carcinoma transplanted mice-hybrids BDF1), subcutaneously. Inoculum was 5·106tumor cells. ISS is adavale joint action FB-13 and cisplatin. Assessment criterion served as an index of inhibition of lung metastases (MRI%). With the introduction of one of cisplatin MRI=80%, at joint application with FB-13 MRI=100%.

Example 7. Experimental melanoma b-16 transplanted subcutaneously to mice-hybrids BDF1. Inoculum was 5·106tumor cells. Investigated the combined effect of FB-13 and cisplatin. Assessment criterion served as an index of inhibition of lung metastases (MRI%). With the introduction of one of cisplatin MRI=52%, when combined with the introduction of FB-13 MRI=100%.

Tests for acute toxicity was performed in a group of experimental Oncology, Institute of chemical physics RAS by intraperitoneal administration of drugs in the water mice BDF1. It is shown that the claimed objects are non-toxic at a dose of 1000 mg/kg This data allows us to include the claimed connection to discharge toxic compounds. The use of these compounds in minimum doses and in combination with minimal doses of cytostatics, when neither the one nor the other drugs do not have a therapeutic effect separately, allow to completely inhibit the process of metastasis in experimental melanoma b-16 or Lewis lung carcinoma (see Fig.1-4).

In addition, the use of acetamido dicarboxylic acids as a means of enhancing antitumor effect in combination with minimum quantities of ACS the amide and cytostatic (single dose of cytostatics in 4 times lower than therapeutic) to increase efficiency in the treatment of leukemia P-388 (survival of the animals is 100%).

1. The use of dicarboxylic acids of the General formula (2)

where R=HOHNCO; HONHCOCH(OH)CH(OH); HOOCCH2CH2; HOOCCH=CH,

as inhibitors of metastasis and means of enhancing the chemotherapeutic activity of anticancer drugs.

2. Method of strengthening the effectiveness of drugs in cytotoxic cancer chemotherapy, namely, that the cytostatic agent used in combination with derivatives of dicarboxylic acids of the formula 2

where R=HOHNCO; HONHCOCH(OH)CH(OH); HOOCCH2CH2; HOOCCH=CH.

3. The method of inhibition of metastasis, which consists in the fact that the tumor is affected by a combination of known cytostatic and dicarboxylic acids of formula 2

where R=HOHNCO; HONHCOCH(OH)CH(OH); HOOCCH2CH2; HOOCCH=CH.



 

Same patents:

FIELD: organic chemistry, medicine, oncology, biochemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 is chosen from the following order: hydrogen atom, (C1-C4)-alkyl, -COOH, -COO-(C1-C4)-alkyl; R2, R3, R4 and R5 are chosen independently from the following order: hydrogen, halogen atom, (C1-C4)-alkyl-, hydroxy-group, (C1-C4)-alkoxy-group; Y means -CH2-CH2-; X means alkylene chain comprising from 4 to 10 carbon atoms that is saturated or unsaturated and can comprise one double bond, it can be branched or direct, its enantiomers, and its salts with pharmaceutically acceptable acids and bases. Also, invention relates to a pharmaceutical composition possessing inhibitory effect on histone deacetylase activity and comprising active component as compound of the formula (I) in mixture with pharmaceutically acceptable carrier, excipients or diluting agents. Invention proposes tetralone derivatives possessing antitumor activity.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

6 cl, 1 tbl, 14 ex

The invention relates to methods of producing compositions collector for flotation of minerals

The invention relates to new compounds of General formula I

< / BR>
in which R1selected from the group consisting of hydrogen, unsubstituted or optionally substituted aralkyl, unsubstituted or optionally substituted orelkinoservisa, unsubstituted or optionally substituted allyloxycarbonyl, unsubstituted or optionally substituted alkyl and hydroxyamino group; R2selected from the group consisting of hydrogen, unsubstituted or optionally substituted orelkinoservisa, unsubstituted or optionally substituted allyloxycarbonyl, aminosidine group; R3selected from the group consisting of hydrogen, unsubstituted or optionally substituted alkyl and unsubstituted or optionally substituted aralkyl; R4selected from the group consisting of unsubstituted or optionally substituted alkyl and unsubstituted or optionally substituted aralkyl; R5and R6that may be the same or different, each independently selected from the group consisting of hydrogen, unsubstituted or optionally substituted alkyl, unsubstituted or optionally substituted cycle>and R6taken together with the nitrogen atom to which they are attached, form an unsubstituted or optionally substituted heterocyclic group; R7selected from the group consisting of hydrogen, hydroxy, unsubstituted or optionally substituted alkyl and unsubstituted or optionally substituted aralkyl; R8selected from the group consisting of hydrogen, hydroxy, unsubstituted or optionally substituted alkyl and unsubstituted or optionally substituted aralkyl, and R9selected from the group consisting of hydrogen, hydroxy, amino and a group of the formula-X-Y, in which X is selected from the group consisting of unsubstituted or optionally substituted (C1-C6)-alkylene and unsubstituted or optionally substituted phenylene, and Y denotes a group of formula-a-b or a-B, where a is selected from the group consisting of unsubstituted or optionally substituted (C1-C6)-alkylene, imino and unsubstituted or optionally substituted (C1-C6)-alkylamino, and selected from the group consisting of hydrogen, amino, amidino, acylmethyl, unprotected or optionally protected bis (phosphono)methyl, provided that R7, R8and R are not simultaneously represent

Cytotoxic agents // 2187499

The invention relates to new aryl-S(O)n-substituted carboxylic/hydroxamic acids of formula I, where Y represents hydroxy, XONH-where X is H, C1-C6alkyl; R1means H, C1-C6alkyl; R2means H, C1-C6alkyl, C3-C8cycloalkyl, C3-C8cycloalkyl - C2-C8alkyl, tetrahydropyranyl, piperidinyl, -NR6R7where R6means H, C1-C6alkyl, aryl; R7means H, C1-C6alkyl, aryl, aryl - C1-C8alkyl, -SO2NR8R9aryloxyalkyl, C1-C8alkoxycarbonyl, -C(O)-O-CH2Rdwhere Rdmeans phenyl; or a group NR6R7means valinamide; R8and R9independently mean H, C1-C6alkyl; or R1and R2together with the carbon atom to which they are attached form a C3-C8cycloalkyl or possibly substituted lower alkyl piperidinyl or tetrahydropyranyl; R3means H, C1-C6alkyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C8alkyl, aryl, aryl - C1-C8alkyl, piperidinyl, tetrahydropyranyl; R4means H, C1-C6alche are C3-C8cycloalkyl, R3and R4together represent C3-C8cycloalkyl; R5means aryl, possibly substituted

The invention relates to therapeutically active hydroxamic acids and derivatives of carboxylic acids, processes for their preparation, to pharmaceutical compositions containing these compounds and to the use of such compounds in medicine

The invention relates to new derivatives of hydroxamic acids, possessing valuable pharmacological properties, in particular showing the properties of an inhibitor of collagenase, which can be used to delay the development or prevention of diseases of degeneration of the joints, such as rheumatoid arthritis or osteoarthritis, or in the treatment of invasive tumors, atherosclerosis or multiple sclerosis, as well as the way they are received, intermediate products for their production, pharmaceutical preparation and method thereof

The invention relates to therapeutically active derivatives of hydroxamic acids, processes for their preparation, pharmaceutical compositions containing them and to the use of such compounds in medicine

FIELD: medicine, oncology.

SUBSTANCE: one should carry out endoliquor therapy, moreover, after surgical removal of cerebral tumor, in early post-surgical period, it is necessary to fulfill catheterization of subarachnoidal cerebrospinal space at L4-L5 level and apply an endolumbar catheter. Then one should sample 5 ml cerebrospinal fluid and mix it with methothrexate at the dosage of 5 mg and hydrocortisone suspension at the dosage of 50 mg. The mixture should be incubated for 30 min at 37° C to be introduced into subarachnoidal space through endolumbar catheter by flow-type technique. There are 5 such infusions during one therapeutic course at 3-d-long interval. Totally, it is necessary to conduct 3 mentioned courses in combination with 5 cycles of adjuvant systemic polychemotherapy at injecting cytostatics upon autoblood. Application of such complex therapy enables to stabilize generalized tumoral process, increase relapse-free and metastases-free periods and prolong patient's life duration.

EFFECT: higher efficiency of therapy.

3 ex

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating metastatic hepatic disorder in patients with malignant neoplasms. The method of regional polychemotherapy (RPCT) concentrates upon catheterization of proper hepatic artery (PHA) through gastro-omental artery to fulfill intra-arterial RPCT. Moreover, additionally after PHA catheterization it is necessary to catheterize an umbilical vein (UV) due to fulfilling arterio-venous shunting. For this purpose, one should connect catheters introduced into UV and PHA, with the help of a T-joint valve appliance (TVA); before carrying out RPCT it is important to conduct hepatic arterialization due to directing the blood from PHA through UV into the liver by setting TVA valves in position being open for PHA and UV; for carrying out RPCT one should locate TVA valves in position being open for introducing chemopreparations out of the system with a dosing tank of medicinal substances into PHA to carry out the infusion of chemopreparations. Seances for alternating hepatic arterialization and RPCT should be fulfilled daily once a day during the whole course of therapy. The innovation enables to simultaneously increase the concentration of chemopreparations in metastatic hepatic foci, detoxication hepatic function and sensitivity of tumor cells to chemopreparations as a result of additional preliminary oxygenation of hepatocytes.

EFFECT: higher efficiency of therapy.

1 cl, 6 dwg, 1 ex

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating patients with generalized skin melanoma at single and multiple cerebral metastases and extracerebral lesions. The method includes systemic immunochemotherapy. For this purpose, on removing a single cerebral metastasis and melanomatous focus or at multiple cerebral lesions when operation is contraindicated it is necessary to carry out a 2-wk-long course of autohemoimmunochemotherapy, that is: 400 ml patient's autoblood should be sampled into a vial with hemoconservant and after sedimentation it should be divided into 2 equal fractions - plasma and autologous cell suspension (ACS). In separate vials it is necessary to prepare 3 media - 200 ml autoplasma (medium N1) and per 100 ml ACS (medium N2 and N3). One should incubate for 1 h in thermostat at 37° C medium N1 with 100 mg carmustine (mixture N1), medium N2 - with 25 mg metothrexate and 1 mg vincristine (mixture N2), medium N3 - with Reaferon at the dosage of 5×106 IU Reaferon (mixture N3). On the 1st d of the course one should inject mixtures intravenously by drops successively every mixture per 60 min, mixture N2 should be injected repeatedly on the 8th d of the course, mixture N3 should be injected by drops along paracetamol intake thrice weekly during the whole 2-wk-long course of therapy. Additionally, one should fulfill intravenous infusions of 150 mg carboplatin and 15 mg bleomycin upon 200 ml autoblood by drops on the 2nd and 4th d of the course, correspondingly. Totally, one should carry out 3-6 courses. The innovation provides stable regression of neurological symptoms due to decreasing the volume of cerebral metastasis and reactive perifocal cerebral edema and increasing relapse-free and metastasis-free periods and, also, life period in patients.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine, biotechnology.

SUBSTANCE: invention relates to antibodies specifically binding to new human extracellular matrix polypeptides called as RGI; immunoconjugate containing the same and method for selective cell degradation; method for treatment of prostates cancer and metastasis in patients suffering from prostates cancer.

EFFECT: new method for treatment of prostates cancer.

28 cl, 7 ex, 7 dwg

FIELD: biotechnology.

SUBSTANCE: invention relates to inhibitor of matrix metalloproteinases representing extract from fungus Canoderma atrum obtained by using of water and/or lower alcohols as extractant. Also disclosed are pharmaceutical agent for inhibition of tumor metastasis containing of 0.03-10 wt.% of abovementioned extract and foodstuff containing claimed extract.

EFFECT: improved inhibitor of matrix proteinases.

3 cl, 18 ex, 4 tbl

FIELD: medicine, oncology, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions used for inhibition of metastasis or prophylaxis of malignant tumor relapse after the topical therapy. As an active component, compositions contain derivative of polysaccharide comprising polysaccharide with carboxyl group bound with an active substance possessing anti-tumor activity through amino acid or peptide consisting of from 2 to 8 amino acids that are similar or different, or its salt wherein this active anti-tumor substance is represented by derivative of camptothecin of the formula (I) by claim 1 or compound of the formula (II) by claim 1 given in the invention description. The topical therapy involves surgery, radiation therapy, thermotherapy, cryotherapy or laser-burning therapy. Proposed compositions allow providing the high concentration of active substance in tumor metastasis region and prophylaxis of relapses of malignant tumor after carrying out the topical therapy.

EFFECT: valuable medicinal properties of pharmaceutical compositions, improved method of treatment.

9 cl, 1 dwg, 4 tbl, 6 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new sulfonamide derivatives possessing anti-tumor activity, namely to compounds of the formula (I): wherein R6 means hydroxyl; R7 means methyl, isopropyl, isobutyl, benzyl or indole-3-ylmethyl; R8 means hydrogen atom; R9 means phenylene; R10 means thienyl, furyl or pyridyl optionally substituted with lower alkyl or halogen atom. Also, invention relates to their derivatives or pharmaceutically acceptable salts or solvates. Invention describes medicinal agents used in treatment or prophylaxis of cancer and for prophylaxis of metastasis. Also, invention describes a case for treatment of cancer in mammal.

EFFECT: improved treatment method, valuable medicinal properties of agent.

5 cl, 17 tbl, 112 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative of triazaspiro[5.5]undecane of the formula (I): wherein R1 means compound of the formula (1): or (2): wherein G represents a bond, (C1-C4)-alkylene, (C2-C4)-alkenylene or -CO-; ring A represents: (1) C5-10-membered mono- or bicarbocyclic ring or (2) 5-10-membered mono- or bicyclic heterocycle comprising 1-2 nitrogen atoms and/or 1-2 oxygen atoms; substitute R6 means the following values: (1) (C1-C4)-alkyl, (2) halogen atom, (3) nitrile group, (4) trifluoromethyl group and others; R2 represents: (1) (C1-C4)-alkyl, (2) (C2-C4)alkynyl or (3) (C1-C4)-alkyl substituted with a substitute represented in claim 1 of the invention claim; each R3 and R4 represents independently: (1) hydrogen atom, (2) (C1-C4)-alkyl or (3) (C1-C4)-alkyl substituted with 1-2 substituted taken among: (a) Cyc 2 and (b) hydroxy-group (wherein Cyc 2 represents (1) C5-6-membered monocarbocyclic ring or (2) 5-6-membered monocyclic heterocycle comprising 1-2 nitrogen atoms and/or one oxygen atom), or R3 and R4 form in common group of the formula: wherein R26 represents (C1-C4)-alkyl or Cyc 2; R5 represents hydrogen atom or (C1-C4)-alkyl, its quaternary ammonium salt, its N-oxide or its nontoxic salt. Also, invention relates to pharmaceutical composition inhibiting HIV, regulator of chemokine/chemokine receptor and agent used in treatment and prophylaxis of some diseases, such as inflammatory diseases, asthma, atopic dermatitis, nettle rash, allergic diseases, nephritis, hepatitis, arthritis and other diseases that comprise as an active component above described compound of the formula (I) or its quaternary ammonium salt, its N-oxide or its nontoxic salt. Also, invention relates to (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane or its pharmaceutically acceptable salt and pharmaceutical composition based on thereof, and to (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride and pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of derivative and composition.

16 cl, 32 ex

FIELD: medicine, in particular angiogenesis prophylaxis and treatment.

SUBSTANCE: invention relates to 2-cyclooxygenase inhibitors selected from group containing 4-[5-(4-chlorophenyl)-3-phenyl-1H-pyrazole-1-yl] benzenesulfonamide; 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl] benzenesulfonamide; 4-[5-methyl-3-phenyloxazole-4-yl] benzenesulfonamide or pharmaceutically acceptable salts thereof and pharmaceutical composition containing the same in therapeutically effective amount. Said composition are useful in treatment and/or prophylaxis of angiogenesis disorders such as metastasis, eye angiogenesis, diabetic retinopathy, etc. in subjects are needed in such treatment and/or prophylaxis.

EFFECT: new pharmaceuticals for angiogenesis treatment and/or prophylaxis.

5 cl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of triazaspiro[5,5]undecane of the formula (I):

wherein values of radicals R1-R5 are given in the invention claim, ort o their quaternary ammonium salts, N-oxides or nontoxic salts. Proposed compounds possess inhibitory and regulating activity with respect to chemokine/chemokine receptors and can be useful in prophylaxis and treatment of different inflammatory diseases, such as asthma, atopic dermatitis, nettle rash, allergic diseases, nephritis, hepatitis, arthritis or proliferative arthritis and other similar diseases. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I).

EFFECT: improved control method, valuable medicinal properties of compounds.

9 cl, 5 sch, 36 tbl, 70 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes a pharmaceutical composition designated for pain treatment in mammal. Composition contains gabapentin or pregabalin and α-aminoamide. Α-Aminoamide is chosen from the group consisting of (S)-(+)-2-[4-(2-fluorobenzyloxy)benzylamino]propanamide, (R)-(-)-2-[4-benzyloxybenzylamino]-3-phenyl-N-methylpropanamide and (S)-(+)-2-[4-(3-fluorobenzyloxy)benzylamino]-N-methylpropanamide as a single isomer or their mixture. Pharmaceutical composition provides synergistic effect of corresponding analgesic activities without accompanying enhancing symptoms of by-side effects.

EFFECT: valuable medicinal properties of pharmaceutical composition.

6 cl, 2 tbl, 3 ex

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