The method of obtaining derivatives of benzoylbenzoate acid

 

(57) Abstract:

Usage: in medicine, as the product has anti-inflammatory properties. The inventive method to obtain new derivatives of benzoyl-benzene-propanoic acid of General formula: R1has identical or different meanings, hydrogen, C1-C3-alkyl; p=4-6; Y is a simple bond or-C=C-; Z is phenyl, phenyl substituted by halogen or C1-C3-alkoxygroup or C1-C3-alkyl - S-group. Reagent I: where R1-C1-C3-alkyl reagent II: X-/CH2/pY-Z , where X is chlorine, bromine, iodine, mesilate; p, Z, Y have the above meanings. Reaction conditions: reagent I is treated with a reagent II and in the presence of a base and the resulting product highlight or the compound of formula 1, where R - C1-C3-alkyl optionally subjected to alkaline hydrolysis to obtain the compounds of formula 1, where both R are H. table 2.

The invention relates to new substances which counteract the leukotrienes, which are not only effective as anti leukotrienes slow reacting substance of anaphylaxis (LTC4, LTD4and LTE4), but also leukotriene LTB4LTB4is the causative agent Pospolita the allergic reactions of the lung gave evidence, that the derivatives of arachidonic acid, obtained by the action of lipoxygenase refer to different States of diseases. Some of these metabolite of arachidonic acid are classified as members of the family eicosatetraenoic acids, called leukotrienes. Three of these substances are the main components of what used to be called slow-reacting substance of anaphylaxis.

Leukotrien4(LTB4is anti-inflammatory lipid, which is included in the pathogenesis of psoriasis, arthritis, chronic lung diseases, inflammatory bowel disease and other inflammatory conditions characterized by the infiltration and accumulation of the neutrophil leukocytes. The aggregate thus, the leukocytes of neutrophil emit damaging the fabric of the enzyme and reacting substances that cause inflammation. Remedy LTB4thus, is a new therapeutic approach to the treatment of these conditions.

Similarly, the opposing leukotriene D4(LTD4) is used to treat conditions characterized by excessive secretion LTD4including immediate reactions such as asthma and shock.

The literature describes such against the patents NN 108592, 132366 and 132367. It was found that the compounds of the invention are not only opposing LTD4but most of the claimed compounds are opposing LTB4LTD4is an important pathogen in chronic inflammatory diseases such as psoriasis and inflammatory diseases of the stomach. Currently there is no treatment against psoriasis and inflammatory diseases of the stomach.

In accordance with the present invention offers a method of obtaining new compounds of the formula I

where R is the same or different values of hydrogen, C1-C3is alkyl, R is 4-6;

Y simple bond or-C=C-, Z1is phenyl or1-C3-alkoxy-substituted phenyl, halogen, C1-C3-S-.

New counter leukotriene can be used in the treatment of inflammation. Most compounds are opposing LTB4and therefore can be used in the treatment of psoriasis, inflammatory diseases of the stomach and allergic disorders such as asthma, where leukotriene are mediators.

The proposed method of producing derivatives of benzoylbenzoate acid of General formula I bookmark the action with the compound of General formula III

X-(CH2)pY-Z where X is chlorine, bromine, iodine, mesilate, p, Y, Z have the above meanings, in the presence of a base and the resulting product highlight or the compound of formula 1, where R1-alkyl WITH2-C3if necessary, subjected to alkaline hydrolysis to obtain the compounds of formula I where R is hydrogen.

The following definitions apply to various terms that will be referred to in the description.

The term "alkyl WITH1-C3" refers to straight or branched aliphatic radical having 1-3 carbon atoms, e.g. methyl, ethyl, propyl and isopropyl. The term "alkoxy WITH1-C3refers to methoxy, ethoxy, propoxy, isopropoxy. The term "halo" refers to fluorine, chlorine, bromine and iodine.

P R I m e R 1. 2-(6-(Phenylhexa)oxy)-5- (3-(etoxycarbonyl)-benzoyl)bensultap new acid, ethyl ester.

To a solution 2,89 g of 5-(3-(etoxycarbonyl) benzoyl)-2 - hydroxybenzophenone acid, ethyl ester in dimethylformamide was added 370 mg of a 50% dispersion of sodium hydride in mineral oil. After stirring for 1 hour at room temperature was added 2 g of 6-phenylhexane methylophaga ether. Reaction mixture was heated to 65aboutAnd pectoral sodium chloride, dried over sodium sulfate and evaporated to dryness. Purification of the obtained solid over silica gel elwira O-2 ethyl acetate in hexane gave 1.88 g of the desired target substance in the form of butter.

Calculated, 74,74; N 7,16.

WITH33H38ABOUT6.

Found, 74,26; N 7,27.

P R I m e R s 2-13. The following compounds were obtained from the appropriate phenols and the corresponding mesylates in the manner described in example 1.

2. 2-(6-Fenics-5-enyl) oxy) -5-(3-ethoxycarbonyl)benzoyl) benzoylpropionate acid, ethyl ester, yield 64% oil.

Calculated With 74,98; N 6,86.

WITH33H36ABOUT6< / BR>
Found, 75,22; N 7,09.

3. 5-(3-(Etoxycarbonyl) benzoyl) -2-(4-(phenylthio)butoxy) benzoylpropionate acid, ethyl ester, yield 42% oil.

WITH31H34ABOUT6S

Calculated With 69,64; N 6,41.

Found, 68,39; N 6,14.

4. 5-(3-(Etoxycarbonyl) benzoyl)-2- (4-phenoxyethoxy) benzoylpropionate acid, ethyl ester, yield 59% oil.

Calculated With 71,80; N 6,61.

WITH31H34ABOUT6< / BR>
Found, 71,81; N 6,41.

5. 5-(3-(Etoxycarbonyl)benzoyl)-2- (6-(4-methoxyphenyl) -5-hexenyl)oxybenzoates BR>
Found, 70,47; N? 7.04 Baby Mortality.

6. 5-(3-(Etoxycarbonyl) benzoyl)-2- (6-(4-methoxyphenyl) hexyl oxy benzoylpropionate acid, ethyl ester, yield 66.5% of the oil.

Calculated C 72,83; N 7,19.

WITH34H40ABOUT7< / BR>
Found, 72,21; N 7,72.

7. 2-(6-(4-Chlorophenyl) hexyl)oxy-5-(3-(etoxycarbonyl) benzoyl) benzoylpropionate acid, ethyl ester, the yield of 46.7% of the oil.

Calculated With 70,14; N 6,60.

WITH33H37C106< / BR>
Found, With 73,04; N 7,26.

8. 5-(3-(Etoxycarbonyl)benzoyl)-2-(6-(4-florfini)hexenyl) hydroxy benzoylpropionate acid, ethyl ester, yield H, oil.

Calculated With 72,24; N 6,80.

C33H37FO6< / BR>
Found, C 72,50; N 7,28.

9. 5-(3-(Etoxycarbonyl)benzoyl)-2-(6-(4-methylmercapto) -5-hexyl)oxy benzoylpropionate acid, ethyl ester, yield 70% oil.

Calculated With 71,05; N 6,66.

WITH34H38ABOUT6S

Found, 71,19; N 6,85.

10. 5-(3-(Etoxycarbonyl) benzoyl)-2- (6-(3-methoxyphenyl)-5-hexyl) oxy benzoylpropionate acid, ethyl ester, yield 41% oil, IR, MS, NMR.

11. 5-(3-(Etoxycarbonyl)benzoyl)-2- (6-(2-methoxyphenyl)-5-hexyl) oxy benzoylpropionate acid, ethyl ester, o the OIC acid, ethyl ester, yield 94% oil.

IR, MS, NMR.

13. 3-(3-(etoxycarbonyl) benzoyl)-2- (6-(2-methoxyphenyl)hexyl) oxy benzoylpropionate acid, ethyl ester, yield 93%

P R I m e R 14. A solution of 1.88 g of diapir of example 1 dissolved in a mixture of ethanol and water. Add an excess of potassium hydroxide and the solution stirred for 1 h, the Reaction mixture was evaporated in vacuum. To the residue add water and diethyl ether and the resulting layers separated. The aqueous layer was acidified and then extracted with ether. The ether extract is dried over magnesium sulfate and evaporated in vacuum. The residue is recrystallized from a mixture of ethyl acetate/hexane, receiving 1.04 g of 5-(3-carboxybenzoyl)-2-(6-phenylhexa) oxy/benzoylpropionate acid, So pl. 99-101aboutC. elemental analysis Data for N. O.

Calculated With 73,40; N 6,37.

Found, With 76,66; N 6,41.

P R I m e R 15-25. The following compounds were obtained from the corresponding diesters in the manner specified in example 14.

15. 5-(3-carboxybenzoyl)-2-(6-phenylhexa)-oxy)benzoylpropionate acid, yield 62% so pl. 99-101aboutC.

Calculated With 73,040; N 6,37.

WITH29H30ABOUT6.

Found, 73,66; N 6,41.

16. 5-(3-Carboxybenzoyl)-2- (6-f the CLASS="ptx2">

WITH22H28ABOUT6< / BR>
Found, 73,92; N 5,71.

Calculated With 63,52; N 5,13.

WITH27H26ABOUT8.

Found, 63,43; N Is 4.93.

17. 5-(3-carboxybenzoyl)-2-(6-(4-methoxyphenyl)-5-hexenyl)-hydroxy-benzoylpropionate acid, yield 64% so pl. 151-152aboutC.

Calculated With 71,70; N. Of 6.02.

WITH30H30ABOUT7.

Found, 71,46; N 6,11.

18. 5-(3-Carboxybenzoyl)-2- (6-(4-methoxyphenyl)hexyl)-oxy benzoylpropionate acid, output 53,9% so pl. 100-102aboutC.

Calculated With 71,41; N 6,39.

WITH30H32ABOUT7.

Found, 71,57; N 6,22.

19. 2-(6-(4-Chlorophenyl)hexenyl) hydroxy-5-(3-carboxybenzoyl) benzoylpropionate acid, a yield of 75% so pl. 119-121aboutC.

Calculated With 68,43, N 5,74.

WITH29H29CIO

Found, 68,55; N 5,42.

20. 5-(3-Carboxybenzoyl)-2-(6-(4-forfinal) hexenyl)hydroxy benzoylpropionate acid, 51% yield so pl. 118-120aboutC.

Calculated With 70,72; N 5,93.

WITH29H29FO6< / BR>
Found, 70,91; N 6,21.

21. 5-(3-Carboxybenzoyl)-2-(6-(4-methylmercapto)-5-hexyl)oxy benzoylpropionate acid, ethyl ester, yield 73% so pl. 138-141about.

Wycoller)-2-(6-(3-methoxyphenyl)-5-hexenyl)-hydroxy benzoylpropionate acid, exit 45% so pl. 122-125aboutC.

Calculated With 71,70; N. Of 6.02.

WITH30H30ABOUT7< / BR>
Found, 71,94; N 6,18.

23. 5-(3-carboxybenzoyl)-2-(6-(2-methoxyphenyl)-5-hexenyl)-hydroxy benzoylpropionate acid, yield 33% so pl. 132-136aboutC.

Calculated With 71,70; N. Of 6.02.

WITH30H30ABOUT7< / BR>
Found, 71,98; N 6,07.

24. 5-(3-Carboxybenzoyl)-2-(6-(3-methoxyphenyl)hexyl)-oxy benzoylpropionate acid, yield 76% so pl. 88-90aboutC.

Calculated With 71,41; N 6,39.

WITH30H32ABOUT7.

Found, With 71,62; N 6,61.

25. 5-(3-Carboxybenzoyl)-2-(6-(2-methoxyphenyl)hexyl)-oxy benzoylpropionate acid, yield 74% so pl. 125-127aboutC.

Calculated With 71,41; N 6,39.

WITH30H32ABOUT7.

Found, With 71,67; N 6,56.

The compounds of formula 1 are useful in the treatment of any condition, including clinical condition characterized by excessive secretion of leukotrienes B4and D4. These States include hypertensive reactions of immediate type, for example, asthma. Received within a few years evidence has shown the presence of leukotrienes in the saliva of patients with chronic bronchitis (Turniull, et al. Lan. Moreover, Lewis and his colleagues (Int. J. Immunopharmacology, 4, 85 (1982) have recently determined the material in rheumatic synovial fluid, which reacts with antigenic antibodies LTD4. It can determine the existence of a permeability factor leukotriene, which together with LTB4enhances the inflammatory process. Therefore, the compounds described in the invention should reduce some of the symptoms of chronic bronchitis and fibrosis cysts and possibly rheumatoid arthritis due to their ability to counteract the leukotrienes.

The term "excess allocation" leukotriene refers to the number of leukotrienes, sufficient to cause a certain status that is associated with this number. The number of leukotriene, which is considered excessive, depends on various factors, including certain leukotrien, the number of leukotriene needed to cause a certain state depends on the type of mammal. As will be clear to experts in this field, the success of treating mammals suffering from or susceptible to conditions characterized by excessive secretion of leukotriene compounds of formula I is determined by the repression or prevention proc>Male Guinea pigs weighing 200-450 g were killed by decapitation. Removed end portion of the ileum, cleared his cavity, and the fabric is divided into sections 2.5, see Guts were placed in a 10 ml bath tissue, containing a solution of bicarbonate of Krebs following composition in mmol/l: X, 4, 6; CaCl22H2O, 1.2; MgSO47H2Oh, 1,2; NaCl, 118.2; NaHCO3, 24.8; and dextrose, and 10.0. The liquid bath was 37aboutWith and aeronaves 95% oxygen and 5% CO2. In addition, the buffer solution contained 1 to 10-6M atropine to reduce the spontaneous activity of the bowels. Isometric intention was carried out by the sensor Grasse FTO were recorded on a grass polygraph as changes in grams of force. The tissue was used passive force of 0.5, After an appropriate period of alignment were obtained from a single control reactions on net LTD4. After five minutes of exposure to experimental drugs for ulcers, have been added to control the concentration LTD4in the bath tissue. The gut reaction on LTD4in the presence of the drug was compared with the reaction in the absence of drugs.

Then was made a more detailed analysis of antagonism LTD4. In these experiments intestine of Guinea pigs and trachea were paucicellular experimental drugs. Then was repeated curve concentration response to LTD4 in the presence of antagonism. One cloth was only a single concentration of antagonist. The values of Q were calculated by the method of Furchgott (Ann. N. J. Acad Sci, 139, 553 (1967)) using the following equation.

KB< / BR>
The ratio of the dose refers to the concentration of agonist required to achieve 50% of maximum response (CD50in the presence of opposing medication divided by CD50in the absence of antagonism. The calculations were made using the computer and digital graphics. Then, we calculated RA2as the negative logarithm of the KINassuming that the curve of the graph do not differ significantly from unity.

Determination of the antagonism of the compounds of formula 1 are described below.

Antagonism LTB4compounds of the formula I according to example 7, 6, 24.

The compounds of this invention are antagonists of leukotriene receptor4. They are able to block the biological effects of that leukotriene, such as accumulations of neutrophils, chemotaxis, degranulation, as shown by the following experiments.

Quantitative analysis of the operation caused LTB4.

Neutropenia salt of phosphoric acid, contains 2% Oysler glycogen, two male Guinea pigs. After 18 h, the cells accumulated in the abdominal cavity were collected by washing the peritoneal cavity of approximately 100 ml of buffer salts of phosphoric acid containing 10 u/ml heparin. Cells were centrifuged at 200 g for 8 min and the separated liquid was removed. Present in the pill erythrocytes dissolved rapid rotation of cells in 9 ml of ice-cold distilled water for approximately 30 seconds Physiological osmolarity was restored 1.5 ml of 0.6 M KCl. Added 12 ml of buffer salts of phosphoric acid, resuspendable the cells were centrifuged at 200 g for 8 min at 4aboutC. the Pill resuspendable in 5 ml of buffer salt of phosphoric acid. The cell concentration was determined and added additional buffer solution to bring the concentration of cells 1107Jr. This method of selection has led to the accumulation of cells < 90% neutrophil and < 90% viability.

Check aggregation was carried out by determining the number LT4caused by accumulation using single aggregometry of Payton, model 300 C. the Device was calibrated location of the cell containing the cell suspension and tuning knob to 0 so that the or so, arrow showed 9 mV. With this adjustment changes b 8 mV made the recording device to move 200 mm During audit in each cuvette was added 0.5 ml of cell suspension (5 to 10 cells). Then added 5 ml of a solution opytnogo connection. Most of the compounds were first dissolved in dimethyl sulfoxide (DMSO) at 110-2M and then diluted accordingly, the buffer salt of phosphoric acid so that the concentration experienced connection was 110-5110-7M and concentration experienced DMSO was 0.1% or less: some More water-soluble compounds are first dissolved in DMSO at from 0 to 6 to 10-3M and then diluted accordingly, the buffer salt of phosphoric acid, experienced the concentration of DMSO did not exceed 1% After 2 min period equilibrium cells and experimental compounds were added 5 ml of a solution containing l2(100 mM) and MgCl2(50 mM). After 1 min was added 5 ml of buffer salts of phosphoric acid, containing LTB4(3 x x10-7M). Change in amount of light was measured during the last minute. Without experienced connection is the number LTB4usually caused change of the sensor in 120-150 mm In the course of a typical experiment were made a few measurements number is about concentration was determined by the following formula:

Percentage 100

The results of these experiments are given in table.1.

Suppression of communication3N-LTB4with peripheral neutrophile leukocytes.

The efficiency of connections to reduce connection leukotriene4. With a special receptor on the membrane of human neutrophils was measured by using quantitative analysis of link adaptation radioligand developed by Goldman and Gotzl, J. Immunol, 129, 1600 (1982). Other researchers have developed similar samples. Cells used in the test, were isolated by standard technology centrifugation on Ficoll-Hypague precipitation of dextran 70 and hypotonic lysis. Was used the following process. Local donor center has been freshly prepared film of cells in centrifuged blood from two individuals. Cells were mixed and diluted to 484 ml of buffer salt of phosphoric acid containing heparin (10 u/ml) and inactivated by heating the serum of a calf (5X).

It was divided into 20 ml portions, and the portions are deferred on the surface of F-R (12 ml). The material was then centrifuged to 500 g for 40 min at room temperature. The obtained upper layer of platelets and mononuclear cells b 4 ml of the lower layer) and the suspension was mixed. Each ml of this mixture were added 0.33 ml of 6% Mcrodex. After mixing, the cells were precipitated for 2 h at 37aboutC. the resulting pellet of red blood cells was removed, and a pop-up liquid, rich in neutrophils, spin-on 500 g for 10 min at 4aboutC. still present in this pill cells erythrocytes were dissolved keeping in 5-8 ml of ice-cold distilled water for 30-45 C. Then the volume was brought to 50 ml by addition of ice-cold buffer solution and resuspending cells. The suspension was then centrifuged to 300 g for 10 min at 4aboutC. Finally, cells were resuspendable at a density of 2 x x107cells/ml in buffer solution samples. This solution contained a balanced salt solution, Hanks' and 0.1% ovalbumin (pH of 7.3). This separation process resulted in preparations of cells < 90% neutrophils and <90% viability.

The tube connecting the radio-ligand was carried out by incubation of neutrophils (1 of 107cells) from 0.1 to 0.1 PM3N-LTB (150-220 Curie/mmol) and test compound (110-5M and 110-6M) for 10 min at 4aboutC. was Then measured quantity associated3N-LTB4and compared with the number of connected without pilot connection. Analia, then add 20 ml3N-L4diluted in a test buffer solution and finally added 500 ml of cell suspension. After 10 min incubation was added 300 ml of a mixture of phthalate dibutil and dinonyl (7:2) in the tubes were centrifuged for 2 min in microcentrifuge. Measured radioactive connection to pellet cells by scintillation spectroscopy. Made appropriate adjustments for non-specific communication3N-LTB4.

The results are given in table.2.

The compounds or compositions according to the invention can be used orally or through the rectum, tapicerki, parenterally, e.g. by injection and continuous or discontinuous intra-arterial infusion in the form of, for example, tablets, pellets, podanych tablets, capsules, elixirs, gels, suspensions, aerosols, ointments, for example containing 1-10% by weight of active compound with a suitable base, soft and hard gelatin capsules, suppositories, injectively solutions and suspensions in physiologically acceptable medium and sterile packaged powders absorbed on the support for receiving the injection. Mainly for these purposes, the composition can be dosed in a separate form, preferably each dosage sowedane through the rectum) the compounds of formula 1. Can be applied dose from about 0.5 to about 300 mg/kg / day, preferably 0.5 to 20 mg/kg of the active ingredient, although of course it is clear that the amount of compound or compounds of formula 1, which should be applied will be determined by a physician taking into account all the circumstances, including the condition that should be treated used connection method and so the preferred dose not limit the boundaries of the invention.

The compositions according to the invention typically include at least one compound of formula 1 is mixed with carriers or diluted by a carrier or placed in swallow the media, in the form of capsules, gelatin capsules, paper or other container or ejectable container, such as ampoules. The carrier or diluent may be solid, semi-solid or liquid substance, which serves as the binder, the environment for active therapeutic substance.

Some examples of the diluents or carriers which can be used in the pharmaceutical compositions of the invention are lactose, dextrose, sucrose, cubital, mannitol, propylene glycol, liquid paraffin, white soft paraffin, kaolin, microcrystalline cellulose, silica compound is I, peanut butter, salinity, tragakant, gelatin, syrup, methyl cellulose, coconut oil, ethoxylated esters, oil of Theobroma, monolaurate polioksietilena sorbitan, ethyllactate, alerby alcohol and trichloronitromethane, DICHLORODIFLUOROMETHANE and dichlorotetrafluoroethane. In the case of tablets can be applied grease to avoid use in car manufacturing tablets. For these purposes may apply stearates of aluminum, magnesium and calcium, talc or mineral oil.

Preference is given to such pharmaceutical forms as capsules, tablets, suppositories, injections, creams and ointments. Particular preference is given to compositions for inhalation, for example, aerosols for oral administration.

In U.S. patent 4 661 501 discusses related compounds. In example 43 of the aforesaid U.S. patent describes the connection 5-[4-(4-benzoyl-3-hydroxy-2-propylenoxide)butyl] tetrazole. Following the described procedure, the connection of the prototype and the corresponding compounds of this application were subjected to tests for their inhibitory activity against the binding of leukotriene4a tritium labeled with peripheral human neutrophils. These compounds tested at various concentration is E. For the specified connection on the prototype of the calculated value IC50was 8.1 mm, and for the compounds of the present invention, the IC50had the following values:

Example IC50mm

25 0,19

26 0,19

27 0,014

28 0,53

29 0,10

30 0,32

32 0,096

33 0,025

34 0,13

35 0,14

Based on these data, we can assume the obvious advantage of the compounds of the invention, compounds are of moderate toxicity.

The METHOD of OBTAINING DERIVATIVES of BENZOYLBENZOATE ACID of General formula I

< / BR>
where R, same or different, hydrogen, C1-C3-alkyl;

p 4 6;

Y simple bond or-C=C-;

Z is phenyl, phenylselenenyl halogen or1-C3alkoxygroup or1-C3-alkyl-S-group,

characterized in that the compound of General formula II

< / BR>
where R1-C1-C3-alkyl,

subjected to interaction with the compound of General formula III

X-(CH2)pY-Z

where X is chlorine, bromine, iodine, mesilate;

p, Z, Y are the specified values,

in the presence of a base and the resulting product produce or compound of formula I, where R1-C1-C3-alkyl optionally subjected to alkaline hydrolysis is

 

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3 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: method for alkoxyphenol production comprises O-alkylation of at least one hydroxyphenol to form at least one alkoxyphenol, at that, the said reaction is carried out using an O-alkylating agent, an aqueous solvent containing a Bronsted base and an organic solvent with a base/O-alkylating agent ration in the range of 0.5 to 1.5 moles of base per mole of O-alkylating agent, with an O-alkylating agent/hydroxyphenol ratio in the range of 0.5 to 2 moles of O-alkylating agent per mole of hydroxyphenol and with an organic solvent/hydroxyphenol ratio of less than 280 ml, preferably in the range of 10 to 250 ml and more preferably in the range of 50 to 150 ml of an organic solvent per mole of hydroxyphenol. One of the versions of the alkoxyhydroxybenzaldehyde production method comprises preparation of alkoxyphenol from hydroxyphenol by the foregoing method and a reaction of the aldehyde group addition to the resulting alkoxyphenol to obtain the corresponding alkoxyhydroxybenzaldehyde, preferably by condensation reaction between alkoxyphenol and glyoxylic acid, followed by oxidation of the resulting compound.

EFFECT: proposed method for alkoxyphenol production allows the desired product to be obtained in good yield and high purity with high conversion of initial hydroxyphenol.

11 cl, 3 dwg, 7 ex

FIELD: organic chemistry, pharmacy, pharmacy.

SUBSTANCE: invention relates to novel compounds designated for delivery of active substances to tissues of the following formula: wherein values of radicals R1-R7 are determined in claim 1 of the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to compositions designated for delivery of active substances to tissues and containing: (A) active substance and (B) at least one compound designated for delivery of active substance to animal tissues of the formula: wherein values of radicals R1-R7 are determined in claims 3-5 of the invention claim. Also, proposed invention relates to a standard medicinal formulation designated for delivery of active substances to body tissues and to a method for preparing indicated compositions and administration of substances for their delivery to body tissues.

EFFECT: valuable properties of compounds.

23 cl, 11 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 2-[4'-(2",6"-dimethylphenoxy)benzoyl]benzoic acid which can be used as a by-product in the synthesis of polyarylene phthalides with valuable properties. A method for preparing acid I in 77% yield from 2-(4'-fluorobenzoyl) benzoic acid and 2.6-dimethylphenol in the presence of K2CO3 with two-stage heating: first in a mixture of N,N-dimethylacetamide with chlorobenzene until the azeotropic distillation of water and chlorobenzene is completed, then only in N,N-dimethylacetamide.

EFFECT: increased quality of output.

3 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R1 and R2 represent hydrogen atom; R3 represents benzyl, substituted -O(C1-4alkyl); R5 represents methyl; R6 represents C1-6alkyl; R11 and R12 together form 5-membered heterocyclyldiyl of structure R19 andR20 are independently selected from C1-6alkyl; R13 represents fragment ; R16 represents NO2, R14, R15, R17, and R18 represent hydrogen atom.

EFFECT: compounds of formula (VII) as intermediate products for obtaining macrolides.

6 cl, 18 dwg; 3 ex

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