Amides of sulfamido and sulphonilecarbomide-2-carboxylic acids, processes for their preparation and pharmaceutical composition

 

(57) Abstract:

Amides of sulfamido and sulphonilecarbomide-2-carboxylic acids of the formula I, where A = R3and B = -X-NR6R7or B = R3and A = -X-NR6R7; X is a simple bond or-CO-; R1, R2, R3- same or different and mean hydrogen, unsubstituted WITH1-C4-alkyl, -(C1-C6)-alkoxy, fluorine, bromine; R4, R5- independently from each other - H, C1-C8alkyl, C6-C10-aryl, C7-C11ar-C1-C6-alkyl, C1-C8-alkyloxy may once substituted by hydroxy, carboxy, C1-C6-allyloxycarbonyl,1-C6-alkoxy; R6-H, C1-C6-alkyl, physiologically acceptable monovalent cation Na+, K+; R7- the remainder of the formula II (with the exception of SO2H). Y-[C-U]r-D-W, where Y,-SO2;- Link1-C8-aliphatic alcander; U is a bond, -O-; D is a bond; W is N, thienyl,6-C10-aryl, and U represents-O - in case With no means of communication, and W is preferably substituted, for example, a group-O-(CH2)xCfH(2f+1-q)Fq; f = 1-8; q = 0.1 to(2f+1), r = 1,2; X = 0-8. Used as a pharmaceutical to the ATA and derived sulfonic acid, with the subsequent interaction of the compounds with the amine. Compound I where X is-CO-, derived from a carboxylate ester pyridine-2-carboxylic acid. 2 s and 5 C.p. f-crystals, 1 PL.

The invention relates to Amida sulfamido and sulphonilecarbomide-2-carboxylic acids and their use in pharmaceutical compositions for the treatment of fibrosis.

Compounds inhibiting the enzymes Proline - and lizingodatelyu, through its influence on specific collagen hydroxylation reactions have a very selective inhibitory effect on collagen synthesis. In the course of these reactions under the action of frumento Proline - and lizingodateley is hydroxylation associated protein Proline, lysine, respectively. The suppression of these reactions under the action of the inhibitors are not formed completely gidroksilirovanii, not having a normal functional ability of the collagen molecule, which have only small quantities are able to move from the cells into the extracellular space. In addition, this is not fully gidroksilirovanii collagen cannot be embedded in a collagen matrix and is therefore very easy proteolytic usecollin.

Therefore, inhibitors prolylhydroxylase can find application in the treatment of diseases, the clinical picture which is largely determined by the deposition of collagen. Such diseases include, in particular, fibrosis of the lung, liver and skin (scleroderma), as well as atherosclerosis.

It is known (K. Majamaa and others, Eur. J. Biochem. 138 (1984) 239 - 245), what pyridine-2,4 - and pyridine-2,5-dicarboxylic acid are effective inhibitors of the enzyme prolylhydroxylase. However, in the case of cell cultures, these compounds have effective inhibitory effect only at very high concentrations (Tschank, G and others, Biochem.J. 238 (1987) 625 - 633).

In the Federal Republic of Germany patent A 3432094 described the use of diesters pyridine-2,4 - and pyridine-2,5-dicarboxylic acid with 1-6 carbon atoms in the ether part as a drug for inhibiting Proline - and lingeries.

However, these (lower) alkylated diesters have the disadvantage that they are too quickly broken down in the body with the formation of acids and therefore place them in the cage yourself in high enough concentrations. Therefore, they are unsuitable for direct use as drugs.

In the m number of carbon atoms) diesters and diamides pyridine-2,4 - and pyridine-2,5-dicarboxylic acid, effectively inhibiting the synthesis of collagen in animal experiments.

The present invention was to obtain compounds with stronger antifibrotics action in comparison with known compounds.

The solution of this problem was that the amides of sulfonamide and sulfonamidophenylhydrazine-2-carboxylic acids of General formula 1

< / BR>
where A = R3and B = -X-NR6R7or B = R3and A = -X-NR6R7X - means is a simple bond or-CO-;

R1, R2, R3- same or different and mean hydrogen, unsubstituted C1-C6-alkyl, -(C1-C6) alkoxy, halogen, in particular fluorine or bromine;

R4and R5independently of one another denote hydrogen, C1-C8-alkyl, C5-C10-aryl, C7-C11ar-C1-C6-alkyl, C1-C8-alkyloxy may once substituted by hydroxy, carboxy, C1-C6-allyloxycarbonyl, C1-C6-alkoxy;

R6means hydrogen, C1-C6-alkyl, - physiologically acceptable monovalent cations, in particular Na+, K+;

R7means the residue of formula II (except in - SO2H)

Y - [C-U is practical C1-C8-alcander;

U represents a bond, -O-;

D means the connection;

W means hydrogen, thienyl, C6-C10-aryl;

and U represents-O -, if C does not mean a relationship, and W is preferably substituted, for example, by the group;

-O-(CH2]xCfH(2f+1-q)Fq,

f = 1-8, preferably 1-5;

q = 0.1 to(2f+1).

The most preferred compounds of General formula 1 in which W is substituted by 1-2 groups, including: halogen, trifluoromethyl, C1-C8-alkyl, C6-C10-aryl, C1-C8-alkoxy, C1-C8-alkoxy-C1-C8-alkyl, C6-C10-aryloxy, N-(C1-C8-allylcarbamate, N,N-di-C1-C8-allylcarbamate, N-(C3-C8-cycloalkylcarbonyl, N-(C1-C8)- alkyl-N((C6-C10)aryl-(C1-C8)alkyl)carbarnoyl, N-(C1-C8)-alkyl, C6-C10-arylcarbamoyl, N-C1-C8- alkoxycarbonyl, C1-C8-alkanoyl-N-C1-C8-alkylamino, C6-C10-aryloxy-C1-C8-alkanoyl - N-(C1-C8)-alkylamino, C1-C8-alkanolamine, cyclo C3-C8-alkanolamine, C6-C10ar-C1-C8-alkanolamine-C1-C6-alkanolamine - C1-C8-alkyl, C6-C10-aryloxy-C1-C8-alkanolamine, C6-C10-aroyl-N-(C1-C8)-alkylamino, (C7-C11-ar-(C1-C6-alkanoyl-N- (C1-C10)-alkylamino, C1-C8- alkanolamine-C1-C8-alkyl, C3-C8- cycloalkanones-C1-C8-alkyl,

C6-C10-aroylamino-C1-C8-alkyl, C7-C11ar-C1-C8-alkanolamine - C1-C8-alkyl. The object of the present invention is also a method of obtaining compounds of General formula I, where X represents a simple bond,

R1, R2, R3the same or different and mean hydrogen, unsubstituted C1-C6-alkyl, -(C1-C6)-alkoxy, halogen, in particular fluorine or bromine;

R4and R5independently of one another denotes hydrogen, C1-C8-alkyl, C6-C10-aryl, C7-C11ar-C1-C6-alkyl, C1-C8-alkyloxy may once substituted by hydroxy, carboxy, C1-C6allyloxycarbonyl, C1-C6-alkoxy;

R6means hydrogen, C1-C6-alkyl, - monovalent fisiologicas-SO2H)

Y-[C-U)r-D-W

where Y means SO2;

C means the bond or unbranched or branched aliphatic C1-C8-alcander;

U represents a bond, -O-;

D means the connection;

W stands for hydrogen, thienyl, C6-C10-aryl;

and U represents-O -, if C does not mean a relationship, and W is preferably substituted, for example, by the group;

-O-(CH2]xCf+1-q)Fq,

f = 1-8, preferably 1-5;

q = 0.1 to(2f +1);

by interacting aminopyridine-2-carboxylate of formula II

< / BR>
where A'=R3and B'=-other6or A'=-other6and B'=R3,

subjected to interaction with the sulfonic acid derivative of General formula 3

Z - R7< / BR>
where Z is tsepliaeva group,

and the resulting compound II, where A' = R3, B'=-NR6R7or A'=-Nr6R7and B' = R3,

subjected to interaction with the amine of the formula

H-NR4R5,

with the formation of compounds of General formula 1.

The subject of the invention is a method of obtaining the compounds of formula 1 in which X is-CO-;

R1, R2, R3- same or different and mean hydrogen, unsubstituted C1-C6-AOT another denote hydrogen, C1-C8-alkyl, C6-C10-aryl, C7-C11ar-C1-C6-alkyl, C1-C8-alkyloxy may once substituted by hydroxy, carboxy, C1-C6allyloxycarbonyl, C1-C6-alkoxy;

R5means hydrogen, C1-C6-alkyl, - physiologically acceptable monovalent cations, in particular Na+, K+;

R7means the residue of formula II (except in - SO2H)

Y - [C - U]r-D-W,

where Y means SO2;

C means the bond or unbranched or branched aliphatic C1-C8-alcander;

U represents a bond, -O-;

D means the connection;

W stands for hydrogen, thienyl, C6-C10-aryl;

and U represents-O -, if C does not mean a relationship, and W is preferably substituted, for example, by the group:

-O-(CH2]xCfH(2f+1-q)Fq,

f = 1 to 8, preferably 1 to 5;

q = 0.1 to(2f + 1);

according to which the carboxylate ester pyridine-2-carboxylic acid of formula 7:

< / BR>
where A = R3, B = CO2H or A = CO2H and B" = R3,

subjected to interaction with the sulfonic acid derivative of formula 8:

R6HNR7VIII

and abrazos is subjected to interaction with the amine of formula 6:

HNR4R5,

where R1, R2, R3- same or different and mean hydrogen, unsubstituted C1-C6-alkyl, -(C1-C6) alkoxy, halogen, in particular fluorine or bromine;

R4and R5independently of one another denote hydrogen, C1-C8-alkyl, C6-C10-aryl, C7-C11ar-C1-C6-alkyl, C1-C8-alkyloxy may once substituted by hydroxy, carboxy, C1-C6allyloxycarbonyl, C1-C6-alkoxy;

R6means hydrogen, C1-C6-alkyl, - physiologically acceptable monovalent cations, in particular Na+, K+;

R7means the residue of formula II (except in-SO2H)

Y - [C - U)r-D-W,

where Y means SO2;

C means the bond or unbranched or branched aliphatic C1-C8-alcander;

U represents a bond, -O-;

D means the connection;

W stands for hydrogen, thienyl, C6-C10-aryl;

moreover, U represents-O -, if C does not mean a relationship, and W is preferably substituted, for example, by the group:

-O-(CH2]xCfH(2f+1-q)Fq,
listed schemes.

Scheme 1 illustrates the formation of compounds of formula 1 in which X represents a simple bond (see end of text).

5-aminopyridine-2-carboxylates of formula 1 is subjected to interaction with derivatives of sulfonic or carboxylic acids of formula 2, in which Z denotes a hydroxyl group or useplease group which can be split nucleophile, for example F, Cl, Br, J or toilet. The above reaction is carried out in an environment aprotic organic solvent or solvent mixture. Suitable, in particular, are the following solvents: dichloromethane, carbon tetrachloride, butyl acetate, ethyl acetate, toluene, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, nitromethane and/or pyridine. The reaction can be carried out in the presence of kislorodsvyazyvayushchei tools, such as ammonia, triethylamine, tributylamine, at a temperature of 0 - 180oC, preferably 0 to 80oC. To produce compounds in which Z signifies gidroksilnuyu group that can be used are known in the chemistry of peptides condensation methods.

The compounds of formula 1a can also be obtained by saponification of compounds of formula 3 in pyridine-2-karamanova acid to 5 or by direct interaction of the compounds of formula 3 with amines of formula 5. If desired, the compounds can be oxidized to the pyridine-N-oxides of the formula 1b.

In General, these methods of oxidation are described, for example, in "E. Klinsberg, Pyridine and its Derivitives, Interscience Publishers, New York, 1961, Part 2, 93".

Oxidation using hydrogen peroxide is described, for example, in "E. Ochiai, J. Org. Chem. 18, 534 (1953)".

The original connection is described in detail in the applications Germany P 3826471.4, 3828140.6, 3924093.2, 4001002.3, as well as in patents Germany A 3703959, 3703962 and 3703963.

Obtaining compounds of formula 1 described N. Finch and others in J. Med. Chem. (1978), T. 21, page 1269 and Schneider and Harris, J. Org. Chem. (1984), T. 49, page 3683.

The above sequence of reactions according to scheme 1 for compounds of formula 1a or 1b with sulfonamidnuyu group in 5-position can also be used to obtain compounds containing such sulfonamidnuyu group in 4-position. At the same time as the original use of the compounds of formula 1 in which X is a bond, Y = SO2, R4means a hydrogen atom, and R5- oxyalkyl, alkoxyalkyl or its derivative, obtained from suitably substituted derivatives of sulfonic acid of formula 2 and the methyl esters of 4- (or 5) amino-pyridine-2-carboxylic acid of formula 1 and the subsequent am is ineni formula 1, have X = -CO-, and Y = SO2,

i) derivatives of pyridine-2-carboxylic acids or the corresponding esters of formula 11 is subjected to interaction with amines of formula 5 or

ii) derivatives of pyridine-5-carboxylic acids of formula 12 is subjected to interaction with sulfonamidnuyu derivative of formula 9, or

iii) derivatives of amides pyridine-5-carboxylic acids of the formula 13 is subjected to interaction with derivatives of sulfonic acids of the formula 2 (see scheme 2) with compounds of formula 12, 13 respectively, are obtained from compounds of formula 7 by known methods.

Scheme 2 illustrates the formation of compounds of formula 1a or 1b, in which X = -CO-, and Y = SO2(see end of text).

According to CA (so 68, 1968, 68840 h) of the substituted pyridine-2,5-dicarboxylic acids of formula 7 in the conditions of the esterification reaction can be obtained 5-carboxylate esters of pyridine-2-carboxylic acid. Suitable, for example, is the reaction of esterification with methanol in the presence of sulfuric acid. However, the duration of the reaction is chosen so that a complete etherification with the formation of diapir proceeded only to a minor degree, respectively, to which by-products of the diesters can be separated from onoh formula 9 (Y = SO2). While it may be appropriate to activate both the source reagent by means of auxiliary reagents (Houben - Weyl: Methods der Organischen Chemie, Band IX, Kapitel 19, pages 636 - 637).

As reagents for activating carboxylic acids can be used well-known specialists agents such as thionyl chloride, oxalicacid, pivaloyloxy or derivatives of the esters Harborview acid. It is not always necessary to allocate these activated derivatives of compounds of formula 8. In most cases, it is advisable after receiving them in situ or in the form of a crude product subjected to interaction with sulfonamidnuyu derivative of formula 9.

It is advisable first to subject the compounds of formula 9 interaction with an inorganic or organic base, such as hydroxide, carbonate, alkoxide, hydride or Amida sodium or potassium hydroxide, ammonia, triethylamine, tributylamine, pyridine, at -20 to +150opreferably 0 to 80oC, and then the resulting reaction mixture is subjected to interaction with the compound of the formula 8 or its activated form. The reaction should be carried out in an inert solvent, such as methylene chloride, methanol, ethanol, acetone, ethyl ether uksu, is metilsulfate or mixtures thereof. Alternatively the esters of formula 11 can be obtained using a standard used for condensation reagents such as a mixture of N,N-dicyclohexylcarbodiimide and 4-N, -N-dimethylaminopyridine).

The interaction of esters of pyridine-2-carboxylic acid of formula 11 with amines of the formula HNR4R5leads to the formation of compounds of formula 1a' in accordance with the present invention.

Another option for obtaining compounds of formula 1a' of the compounds of formula II (R = lower alkyl) omelet in derivatives of pyridine-2-carboxylic acid of formula II (R = H), which are then known in the chemistry of peptides expose methods of combination reaction with amines HNR4R5with the formation of the inventive compounds of the formula 1a'.

Getting pyridine-N-oxide formula 1b' is carried out in accordance with the above scheme 1 (reaction with the translation of the compounds of formula 1a compound of formula 1b).

The above sequence of reactions according to scheme 2, in which the obtaining the compounds of the formula 1a or 1b' with carbondisulphide group in 5-position, may also be used to obtain such type of compounds, with the organisations of General formula 7'

< / BR>
The compounds of formula 1 in which X = CO, Y = SO2, R4means a hydrogen atom, and R5- oxyalkyl, alkoxyalkyl or its derivative, obtained by the interaction appropriately substituted sulfonamides of the formula 9 and methyl ester pyridine-2 or -4(5)-carboxylic acid and subsequent aminolysis the resulting compounds of the formula II (R = lower alkyl) with the appropriate amines.

To obtain compounds of formula 1, in which NR4R5means glycol, the compounds of formula 3 and 11 (R = lower alkyl) omelet in derivatives of pyridine-2-carboxylic acid of formula 4 and 11 (R = H), which are then subjected to the condensation reaction with the corresponding derivative of glycine. Free amides of gizela, in which NR4R5means NHCH2CO2H, is obtained by saponification of amides pillowy esters or catalytic hydrogenation of the benzyl ester of gizela.

To obtain the compounds of General formula 1 (1a, 1b, 1a', 1b') in schemes 1 and 2 are compounds in which R6means a hydrogen atom. After that, preferably carry out the reaction of salt formation with the formation of compounds in which R6means physiologically acceptable cation. As the how, for example, 2-ethanolamine, 3-propanolamine, 2-methoxyethylamine, 2-amoxicillin and ,,- Tris-(oxymethyl)methylamine (=tributer, trimeton) or basic amino acids, such as histidine, arginine and lysine.

Proposed in accordance with the present invention the compounds of formula 1 possess valuable pharmacological properties and are distinguished, in particular, antifibrotic activity.

I believe that inhibitors of prolyl-4-hydroxylase suitable antifibrosis agents.

The enzyme prolyl-4-hydroxylase has the alternative title - procollagen-Proline, 2-oxoglutarate-4-dioxygenase (Dorland''s Ilustrated Medical Dictionary, 27 th Edition, W. B. Saunders Co., 1988). Prolyl-4-hydrosylate is the enzyme class oxidoreductases that catalyze the reaction in the biosynthesis of collagens. According to Kaule and Gunzler, Analytical Biochemistry 184, 291 - 297 (1990) excision of synthesized amino acid hydroxyproline is involved in hydrogen bonds, which are necessary for the structure and function of collagen at 37oC. the ability of the compounds according to the invention to inhibit enzymatic activity of prolyl-4-hydroxylase can be determined by measuring the amount of succinate formed from the initial 2-oxoglutarate in pikh agents. The activity of compounds on the inhibition of prolyl-4-hydroxylase is expressed as the dilution of the original concentrated solution, which gives 50% inhibition of the enzyme. Thus, the greater the dilution, the stronger the ability of compounds to inhibit the enzyme.

To determine the effect of inhibition of prolyl-4-hydroxylase compounds according to the invention was investigated in experiments on perfusion of the liver. Inhibitory activity was measured in the resulting perfusion solution.

Method: fed male rats of Wistar with body weight 200 - 300 g were anestesiologi pentobarbital (5 mg/100 g, intraperitoneally). After catheterization of the portal vein, the liver was washed with 100 ml of physiological solution with the addition of heparin (5 IU/ml) at 37oC for 3 minutes, during which occurred the outflow through the notched caudal Vena cava. After that, the body cut out and connected with the device for perfusion, and spent perfusion within 2 hours of the recirculating medium (100 ml) at a rate of 30 ml/min Perfusion medium is RBB (buffered Krebs-ringer), containing bovine erythrocytes. Bovine blood was mixed with citrate solution in a ratio of 1:1 immediately below. The mixture was centrifuged for 10 minutes (600. the target perfusion medium containing 33.3% of the sediment erythrocytes and 66.7% ISC (Schimassek, H., (1963): Biochem. Z. 336, 460 - 467).

The compositions used in this test solutions following:

Citrate solution:

Monohydrate glucose - 22.6 g

Trinatriytsitrat - 4.0 g

Citric acid is 5.5 grams

NaCl - 4.2 grams

The addition of 1,000 ml of distilled water

b) Buffered Krebs - ringer (RBB)

NaCl 8.0 g

KCl - 0.2 g

NaHCO3H2O - 1.0 g

NaH2PO4H2O - 0.1 g

CaCl2- 0.2 g

MgCl26H2O - 0.1 g

Bovine albumin - 16.0 g

Adding 898 ml of distilled water and bring the pH to 7.4.

Apparatus for perfusion (Ryoo, H. and Tarver, H., (1968); P. S. E. B. M. 128, 760 - 772).

A Central element of the apparatus was a cylinder with adjustable temperature with the inserted base as a support for the body. The exhaust pipe is extended, and the lower end of this pipe is attached to the peristaltic pump. When returning the perfusion solution to the organ it passes through the heat exchanger (glass spiral), which maintains the temperature of the perfusion solution 37oC. the perfusion solution on two cylinders were barbotirovany a mixture of CO2/O2(the volume ratio of 5: 95) at a rate of 70 ml of gas per minute. For PR is of the perfusion solution in that place, where the perfusion solution came in the liver at certain points in time.

Treatment:

The investigated compounds were added to the perfusion solution of the liver at time 0 and 65 minutes at a concentration of 2 to 100 µg/ml After 120 min of perfusion was selected aliquot of perfusion solution.

Analytical methods:

Inhibitory activity of the metabolites formed during the 2-hour period of perfusion in the liver, measured in the analysis with prolyl-4-hydroxylase in vitro. The enzyme isolated from 14-day-old embryos of chickens (Tuderman, L., Kuutti-Savalainen, E. R. and Kivirkko, K. 1. (1975) Eur J. Biochem. 52, 9 - 16). Test the enzymatic activity is conducted according to Kaule, G. and Gunzler, V. , (1990) Anal. Biochem. 184, 291 - 297. Curves dose-response obtained by using undiluted perfusion solution and liver perfusion solution with serial dilutions.

The results of the above tests, obtained for various compounds according to this invention, shown in the table at the end of the descriptions in the form of dilution of the perfusion solution, at which there is 50% inhibition of the enzyme prolyl-4-hydrolases). Non of the examples in the table correspond to the numbers of the examples.

While conducting experiments connections in accordance with the present invention showed activity in the who analysis propeptide with the terminal nitrogen atoms of collagen type III or cross-linked domains with the terminal nitrogen atoms or carbon type IV collagen (7-collagen, accordingly, collagen type IV NC1) in serum.

For this purpose, define the concentration of hydroxyproline, procollagen III-petide, 7-collagen and collagen-NC type IV in the liver

(a) untreated (control) rats;

b) rats, which were administered carbon tetrachloride (CCl4control);

c) rats, which were first introduced CCl4and then the connection in accordance with the present invention (these test methods described Rouiller C Euperimental toxic injury of the liver in The liver, C. Rouiller, I. 2, 57 335-476, New York, Academic Press, 1964).

The compounds of formula 1 can be used as medicaments in the form of pharmaceutical preparations containing them, if desired, in combination with pharmaceutically acceptable carriers. The proposed connection can be used as medicines, for example, in the form of pharmaceutical preparations containing these compounds in a mixture with suitable for domestic, percutaneous or parenteral administration of a pharmaceutical organic or inorganic carrier, for example water, gum Arabic, gelatin, milk sugar, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols, vaseline, etc.,

For this purpose, -5, preferably from 0.01 to 2.5, most preferably 0.5-1.0 mg/kg/day. In severe cases, this dosage may be increased. In many cases, however, be sufficient and smaller doses. The data focused on adult patients with a weight of approximately 75 kg

Compounds according to the invention used for getting medicines for the treatment and prophylaxis of the aforementioned disorders of metabolism.

The object of the present invention are pharmaceutical compositions containing one or more compounds of formula 1 and/or their physiologically acceptable salts.

Medicines out of the usual, well-known specialist of ways. As drugs pharmacologically active compounds in accordance with the present invention (= active substance) or apply themselves, or preferably in combination with suitable pharmaceutical auxiliary additives or carriers in the form of tablets, pills, capsules, suppositories, emulsions, suspensions or solutions. The concentration of the active substance in such forms is up to about 95, preferably 10-75%.

Peleus are for example, geleobrazovanie, the basis for candles, auxiliary additives in the manufacture of tablets and other carriers of active substances, as well as antioxidants, dispersants, emulsifiers, antispyware, flavorings, conservatives, agents, dissolution or dyes.

The following examples illustrate the invention.

Example 1

(2-oxyethyl)amide 5-[((4-methoxybenzenesulfonyl)amino)-carbonyl] pyridine-2-carboxylic acid.

a) the acid chloride methyl ether pyridine-2-carboxylic acid 5-carboxylic acid.

14.5 g (80 mmol) of methyl ether pyridin-2-carboxylic acid 5-carboxylic acid in 200 ml of anhydrous toluene are mixed from 6.48 ml of thionyl chloride and 2 ml of anhydrous N,N-dimethylformamide. The mixture is heated under stirring for 3 hours at 70oC. thereafter, it was concentrated in vacuo and dissolve the residue in 150 ml of tetrahydrofuran.

b) Methyl ester 5-[((4-methoxybenzenesulfonyl)amino)-carbonyl] pyridine-2-carboxylic acid.

To 16,45 g (88 mmol) of amide 4-methoxybenzenesulfonamide acid in 200 ml of tetrahydrofuran was added when 0oC 19,75 g (176 mmol) of trebuchet potassium. After stirring the mixture for 3 hours at room temperature the f for 3 hours, then add 300 ml of ethyl acetate, twice the extraction is carried out in an aqueous solution of NaHCO3, the aqueous phase is acidified with a concentrated aqueous solution of hydrochloric acid, the extraction is carried out three times with dichloromethane, the extracts are dried, concentrated and the residue is recrystallized from methanol. The result of 9.9 g of colorless crystal product. The pace. plvl. 197-199oC.

c) 2.1 g (6 mmol) obtained in the above example, compounds dissolved in 10 ml of ethanolamine and stir the solution for 5 hours at 50oC. then added 40 ml of water, acidified under cooling with ice (5 to 10oC) concentrated HCl, suck precipitated solid and washed several times with water. The result is a 1.96 g of the target compound as colorless crystals. The pace. plvl. 221-223oC.

Example 2

Amide grillmicrowave ester 5-[((4-methoxybenzenesulfonyl)amino)- carbonyl]-pyridine-2-carboxylic acid.

a) 5-[((4-methoxybenzenesulfonyl)amino)-carbonyl] -pyridine-2-carboxylic acid.

3.0 g (8.6 mmol) of the compound obtained in example 1b) are dissolved in 100 ml of methanol and mix the prepared solution at 0-5demonstrate in vacuum, the residue is dissolved in water, added to the solution at 0-5oC and 17.2 ml (17,2 mmol) of 1 n HCl, suck dropdown precipitate, washed several times with water, receiving the result of 2.58 g of the target compound. The pace. plvl. 234-236oC.

(b) of 1.81 g (5.4 mmol) of the obtained compound in 25 ml of anhydrous tetrahydrofuran was added when 0oC 1.8 g (5,94 mmol) of triethylamine, stirred the mixture at this temperature for 20 minutes, add to it dropwise 0.71 g (5,94 mmol) pivaloyloxy and stirred for 3 hours at 0oC. thereafter, to the mixture of 0.75 g (5,98 mmol) of the hydrochloride licensedialog ether, stirred for 3 hours at 0oC, heated to 20oC and left to stand overnight. To the reaction solution was added followed by 2 n HCl, the extraction is carried out three times with dichloromethane, the extracts are dried, concentrated and the residue is subjected to chromatography on silica gel using as mobile phase a mixture of ethyl acetate and methanol in the ratio of 4:1, the corresponding fractions are concentrated and the residue is recrystallized from diisopropyl ether. The result is 1.44 g of the target compound. The pace. plvl. 150-152oC.

Example 3

(2-oxyethyl)amide 5-[((phenylsulfanyl]-pyridine-2 - carboxylic acid.

The specified connection is produced by way similar to example 1b), using as starting materials of 3.46 g (22 mmol) of the amide benzosulfimide acid, 2,46 g (22 mmol) of trebuchet potassium and 4.0 g (20 mmol) of acid chloride of methyl ester pyridine-2-carboxylic acid 5-carboxylic acid. After recrystallization from methanol obtain 1.6 g of the target compound. The pace. plvl. 197-198oC.

b) the Target connection receive in the same manner as described in example 1c), from methyl ester 5-[((phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid and ethanolamine, in the form of a colorless crystalline substance. The pace. plvl. 249-250oC.

Example 4

(2-oxyethyl(amide 5-[(4-perpenicular)amino] -pyridine-2-carboxylic acid.

a) Methyl ester 5-[(4-perpenicular)amino]-pyridine-2-carboxylic acid.

3.8 g (25 mmol) of methyl ester of 5-amino-pyridine-2-carboxylic acid are dissolved in 75 ml of anhydrous pyridine and the resulting solution portions mixed with 5.8 g (30 mmol) of acid chloride of 4-fermentolisate. The temperature of the reaction solution rises to 35oC. After one hour the reaction solution is evaporated in vacuo, the residue triturated with water, p is 00 mmol) of the obtained compound in 10 ml of aminoethanol heated for hours at a bath temperature of 100oC. Then the reaction mixture is diluted with 100 ml of water, acidified while cooling the diluted twice as concentrated aqueous solution of hydrochloric acid, drop down the precipitate is sucked off, washed and dried. For further purification the crude product is dissolved in 25 ml of cold methanol and mix the solution with water prior to the dimness. The result is 2.9 g of target compound in the form of colorless crystalline material. The pace. plvl. 144 - 146oC.

Example 5

(2-methoxyethyl)amide 5-[(4-perpenicular)amino]-pyridine-2-carboxylic acid.

0.5 g (of 1.61 mmol) of the methyl ester 5-[(4-perpenicular)amino]-pyridine-2-carboxylic acid (the compound obtained in example 4a) is stirred for 3 hours at 70oC in 5 ml of 2-methoxyethylamine. After that, the reaction mixture is evaporated, the residue is dissolved in water, acidified with a solution of concentrated HCl, suck dropdown precipitate, wash it with water. The result of 0.53 g of the target compound as colorless crystals. The pace. plvl. 154oC.

Example 6

(Glycemically ester)amide 5-[(4-perpenicular)amino]-pyridine-2-carboxylic acid.

a) 5-[(4-perpenicular)amino]-PI is eshiwani at 20oC to 100 ml of 1.5 n methanolic NaOH solution and continue stirring for another hour. After that, the reaction mixture is evaporated in vacuo, the residue is dissolved in 30 ml of water and acidified with a solution of concentrated aqueous HCl solution to pH 1. The result is 1.5 g of product. The pace. plvl. 240oC (decomposition).

(b) 1.5 g (5,07 mmol) of the obtained compound in 100 ml of anhydrous tetrahydrofuran are added during 20oC, with stirring, 1.5 ml (about 10.7 mmol) of triethylamine. After 30 minutes, to this mixture at 0oC of 0.53 ml (5.4 mmol) of the ethyl ether of Harborview acid, stirred the mixture for 30 minutes at 0oC add to her 0.65 g (5 mmol) of the hydrochloride licensedialog ether, stirred for one hour at 0oC, heated to 20oC, evaporated in vacuum, mix the residue with 50 ml of a saturated aqueous solution of NaHCO3, the extraction is carried out three times with dichloromethane, the extracts are dried, evaporated and the residue is subjected to chromatography on silica gel, using as mobile phase ethyl acetate. The target connection get mpariwa appropriate fractions, after recrystallization of the residue from diethyl ether. The output of 0.77, Temp. plvl. 146 - 148oC.

Example 7

the(1,1,1-triptoreline)phenylsulfonyl)amino] -pyridine-2-carboxylic acid get in the same way, as with example 4a), starting from 0.5 g (3.3 mmol) of the methyl ester 5-aminopyridine-2-carboxylic acid and 1.3 g (3.5 mmol) of the acid chloride 2,5-bis(1,1,1-triptoreline)benzosulfimide acid. 1,3 crystalline product obtained after treatment of the residue after evaporation water. The pace. plvl. 158 - 160oC.

The target connection receive by way similar to example 4b), on the basis of 0.4 g (0.82 mmol) of the above compound and 5 ml of aminoethanol. After chromatography on silica gel residue after evaporation of the appropriate fractions are recrystallized from diethyl ether. The yield of 0.38 g Temp. plvl. 165 - 167oC.

Example 8

(2-oxyethyl)amide 5-[((4-n-butoxybenzoyl)amino)carbonyl] -pyridine-2-carboxylic acid.

(a) Amide of 4-n-butoxybenzoate acid.

To 10 g of acid chloride of 4-n-butoxybenzoate acid is added dropwise while cooling with ice, 100 ml of methanolic ammonia solution. After stirring for half an hour at 20oC the reaction mixture is evaporated, the residue is mixed with water, acidified to pH 1 to 2 and is sucked off the drop-down sediment. The pace. plvl. the resulting product is equal to 99 - 101oC.

b) Methyl ester 5-[((4-n-butoxybenzoyl)Amil) obtained in the above example, the connection is subjected to interaction with 2.5 g (22 mol) of trebuchet potassium and 5.0 g (25 mmol) of acid chloride of methyl ester pyridine-2-carboxylic acid 5-carboxylic acid. Precipitated potassium salt dissolved in a mixture of dioxane and water and acidified with a solution of 2 n HCl. Precipitated product is sucked off and dried. Output of 1.5, Temp. plvl. 174 - 176oC.

c) the Target compound is obtained by interaction of 0.2 g (0.51 mmol) of the above compound with 5 ml of aminoethanol at 80oC (within one hour). The reaction mixture is diluted with water, acidified, sucked off the drop-down sludge and dried. The result is 0.19 g of a colorless crystalline substance. The pace. plvl. 176 - 178oC.

Example 9

(2-oxyethyl)amide 5[((4-cryptomaterial)amino) carbonyl]-pyridine-2-carboxylic acid.

(a) Amide 4-triftormetilfullerenov acid is obtained from the corresponding carboxylic sulfonic acid by reacting it with methanol solution of ammonia. The resulting crude product is dissolved in water, the solution acidified with falling precipitation is sucked off and dried. The pace. plvl. 143 - 145oC.

b) Methyl ester 5-[((4-cryptomaterial)amino)-carbonyl] -pyridine-2-carboxylic acid.

In the same manner as described in example 1b), spend the interaction between 4.8 g (20 mmol) of the above soy is oil acid 5-carboxylic acid. After evaporation the residue is dissolved in water, the solution acidified with falling precipitation is sucked off and dried. 3.4 g of the obtained crude product (temp. plvl. 210 - 214oC) recrystallized from 75 ml of ethyl acetate. The result is 1.5 g of a colorless crystalline substance. The pace. plvl. 221 - 223oC.

c) the Target compound is obtained from 0.6 g (about 1.5 mmol) previously obtained compound and 5 ml of aminoethanol, which is heated for one hour at 80oC, then cooled, mixed with water, acidified with diluted twice as concentrated HCl, extracted with ethyl acetate, dried, evaporated and recrystallized from diethyl ether. The pace. plvl. 202 - 204o.

Example 10

(2-oxyethyl)amide 5-[((2,5-bis[1,1,1-trichoroethylene] phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The target connection receive in the same manner as described in example 1c, based on the methyl ester 5-[((2,5-bis[1,1,4-cryptometrics]phenylsulfonyl)amino)carbonyl]-pyridine - 2-carboxylic acid and aminoethyl. Crystallization was carried out from diethyl ether, Temp. plvl. 190 - 192oC.

Example 11

(2-oxyethyl)amide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl)-Amini] phenylsulfonyl)-amino)carbonyl]-pyridine-2-carboxylic acid.

Example 13

(2-methoxyethyl)amide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl)-amino)carbonyl]-pyridine-2-carboxylic acid.

Example 14

(Glycemically ester)amide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl)-amino)carbonyl]-pyridine-2-carboxylic acid.

Example 15

Glycolipid 5-[((4-[2,2,2-cryptometrics]phenylsulfonyl)-amino)carbonyl] -pyridine-2-carboxylic acid.

Example 16

(2 acetylamino)glycinamide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 17

(2-oxyethyl)amide 5-[((4-[2,2,3,3,3-pentafluoropropane] phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 18

(2-methoxyethyl)amide 5-[((4-[2,2,3,3,3-pentafluoropropane] phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 19

Ethylamide 5-[((4-methoxybenzenesulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 20

H-butylamide 5-[((4-methoxybenzenesulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 21

Cyclohexylamin 5-[((4-methoxybenzenesulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 22

Benzylated 5-[4-methoxyphenylazo is TurboTax] - phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 24

(Glycemically ester)amide 5-[((4-[2,2,3,3,4,4,4-heptafluorobutyrate]phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 25

(2-oxyethyl)amide 5-[((4-phenoxyphenylacetic)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 26

(2-ethoxyethyl)amide 5-[((4-phenoxyphenylacetic)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 27

(2-methoxyethyl)amide 5-[((4-phenoxyphenylacetic)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 28

(2-oxyethyl)amide 5-[((2-phenylenesulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 29

(Glycemically ester)amide 5-[((2-phenylenesulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 30

(2-oxyethyl)amide 5-[((n-butylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid. The pace. plvl. 168-169oC (after recrystallization from water).

Example 31

(2-methoxyethyl)amide 5-[((n-butylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 32

(Glycemically ester)amide 5-[((n-butylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic cyclotides-2-carboxylic acid. The pace. plvl. 167-168oC (after recrystallization from water).

Example 34

(Glycemically ester)amide 5-[((4-[3-(trifluoromethyl)phenyloxy] - phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 35

(2-methoxyethyl)amide 5-[((1-naphthylmethyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 36

(2-oxyethyl)amide 5-[((1-naphthylmethyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 37

(2-methoxypropyl)amide 5-[((1-naphthylmethyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 38

(Glycemically ester)amide 5-[((1-naphthylmethyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 39

(2-oxyethyl)amide 5-[((2-naphthylmethyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 40

(2-oxyethyl)amide 5-[((phenylmethylsulfonyl)amino)carbonyl] - pyridine-2-karbonovoi acid.

Example 41

(Oxyethyl)amide 5-[((2-phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 42

(2-oxyethyl)amide 5-[((2-(4-forfinal)ethylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 43

(2-oxyethyl)amide 5-[((2-methoxyphenyl)ethylsulfonyl)amino) Carbo is carbonyl] - pyridine-2-carboxylic acid.

Example 45

(Oxyethyl)amide 5-[((4-phenyl-n-butylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 46

(Oxyethyl)amide 5-[((2-Phenoxyethanol)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 47

(2-oxyethyl)amide 5-[((2-(4-pertenece)ethylsulfonyl)amino)- carbonyl] -pyridine-2-carboxylic acid.

Example 48

(2-methoxyethyl)amide 5-[((phenylmethylsulfonyl)amino)carbonyl]- pyridine-2-Carbonell acid.

Example 49

(2-methoxyethyl)amide 5-[((2-phenylethylamine)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 50

(2-methoxyethyl)amide 5-[((2-(4-forfinal)ethylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 51

(2-methoxyethyl)amide 5-[((2-(4-methoxyphenyl)ethylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 52

(2-methoxyethyl)amide 5-[((3-phenyl-n-propylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 53

(2-methoxyethyl)amide 5-[((4-phenyl-n-butylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 54

(2-methoxyethyl)amide 5-[((2-Phenoxyethanol)amino) carbonyl]-pyridine-2-Carbo is-pyridine-2-carboxylic acid.

Example 56

(Glycyl-2-propyl ester)amide 5-[((phenylmethylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 57

(Glycyl-2-propyl ester)amide 5-[((phenylethylamine)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 58

(Glycyl-2-propyl ester)amide 5-[((2-(4-forfinal) ethylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 59

(Glycyl-2-propyl ester)amide 5-[((2-(4-methoxyphenyl) ethylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 60

(Glycyl-2-propyl ester)amide 5-[((3-phenyl-n-propylsulfonyl)- amino)carbonyl]-pyridine-2-carboxylic acid.

Of the acid chloride of 4-carboxylic acid (or 4-carboxylic acid methyl ester pyridine-2-carboxylic acid in a similar way get:

Example 61

(2-oxyethyl)amide 4[((4-[2,2,2-cryptometrics] -phenylsulphonyl)- amino)carbonyl]-pyridine-2-carboxylic acid.

Example 62

(2-methoxyethyl)amide 4[((4-[2,2,2-cryptometrics] -phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 63

(Glycemically ester)amide 4[((4-[2,2,2-cryptometrics] phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 65

(2-ethoxyethyl)amide 4-[((2-phenoxyphenylacetic)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 66

(2-oxyethyl)amide 4-[((2-phenylenesulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 67

(Glycemically ester)amide 4-[((2-phenylenesulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 68

(2-oxyethyl)amide 4-[((n-butylsulfonyl)amino)carbonyl] -pyridine - 2-carboxylic acid.

Example 69

(2-methoxyethyl)amide 4-[((n-butylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 70

(Glycemically ester)amide 4-[((n-butylsulfonyl)amino)- carbonyl] pyridine-2-carboxylic acid.

These connections after oxidation can be also obtained in the form of predin-N-oxides.

The following compounds of formula I in which Z signifies a simple link, can be obtained from the corresponding starting compounds in the same manner as described in example 4, respectively 5, scheme 1:

aminoamide derivatives and glycinamide derivative gain in the same manner as described above.

Example 71

(2-oxyethyl)amide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl)- ylsulphonyl) amino] -pyridine-2-carboxylic acid.

Example 73

(2-methoxyethyl)amide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl) amino)]-pyridine-2-carboxylic acid.

Example 74

(Glycemically ester)amide 5-[((4-[2,2,2-cryptometrics] phenylsulfonyl)-amino)]-pyridine-2-carboxylic acid.

Example 75

Glycolipid 5-[((4-[2,2,2-cryptometrics]phenylsulfonyl)-amino)]- pyridine-2-carboxylic acid.

Example 76

(2-oxyethyl)amide 5[((4-[2,2,3,3,4,4,4-heptafluorobutyrate] phenylsulfonyl)amino)]-pyridine-2-carboxylic acid.

Example 77

(2-methoxyethyl)amide 5[((4-[2,2,3,3,4,4,4-heptafluorobutyrate]- phenylsulfonyl)amino)]-pyridine-2-carboxylic acid.

Example 78

(2-ethoxyethyl)amide 5[((4-[2,2,3,3,4,4,4-heptafluorobutyrate]- phenylsulfonyl)amino)]-pyridine-2-carboxylic acid.

Example 79

(Glycemically ester)amide 5[((4-[2,2,3,3,4,4,4 - heptafluorobutyrate]phenylsulfonyl)amino)]-pyridine-2-carboxylic acid.

Example 80

(2-oxyethyl)amide 5-[((4-phenoxyphenylacetic)amino)] - pyridine-2-carboxylic acid.

Example 81

(2-ethoxyethyl)amide 5-[((4-phenoxyphenylacetic)amino)]- pyridine-2-carboxylic acid.

Example 82

(2-methoxyethyl)amide 5-[((4-phenoxyphenylacetic)amino)]- pyridine-2-CT is howling acid.

Example 84

(glycemically ester)amide 5-[((2-phenylenesulfonyl)amino)] - pyridine-2-carboxylic acid.

Example 85

(2-oxyethyl)amide 5-[((n-butylsulfonyl)amino)]-pyridine-2 - carboxylic acid.

Example 86

(2-methoxyethyl)amide 5-[((n-butylsulfonyl)amino)]-pyridine-2 - carboxylic acid.

Example 87

(Glycemically ester)amide 5-[((n-butylsulfonyl)amino)]-pyridine - 2-carboxylic acid.

Example 88

(2-oxyethyl)amide 5-[((4-[3-(trifluoromethyl)phenoxy] phenylsulfonyl) amino)]-pyridine-2-carboxylic acid.

Example 89

(Glycemically ester)amide 5-[((4-[3-(trifluoromethyl)phenyloxy] - phenylsulphonyl)-amino)]-pyridine-2-carboxylic acid.

Example 90

(2-oxyethyl)amide 4-[((4-phenoxyphenylacetic)amino)] - pyridine-2-carboxylic acid.

Example 91

(2-methoxyethyl)amide 4-[((4-phenoxyphenylacetic)amino)]- pyridine-2-carboxylic acid.

Example 92

(2-oxyethyl)amide 4-[((2-phenylenesulfonyl)amino)] - pyridine-2-carboxylic acid.

Example 93

(2-oxyethyl)amide 4-[((n-butylsulfonyl)amino)]-pyridine-2 - carboxylic acid.

Example 94

(Glycemically)amide 4-[((n-butylsulfonyl)amino)] -pyridine-2 - Carbo is pyridine-2-carboxylic acid.

Example 96

(2-oxyethyl)amide 5-[((4,5-dibromo-2-thienylmethyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 97

(2-methoxyethyl)amide 5-[((4,5-dibromo-2-teilzunehmen) carbonyl]-pyridine-2-carboxylic acid.

Example 98

Ethylamide 5-[((4,5-dibromo-2-thienylmethyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 99

Ethylamide 5-[((5-chloro-2-thienylmethyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 100

(2-oxyethyl)amide 5-[((4-(4,6-dichloro-2-chinolin] phenylsulfonyl)- amino)carbonyl]-pyridine-2-carboxylic acid.

Example 101

(2-oxyethyl)amide 5-[((5-chloro-2-thienylmethyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 102

(3-methoxypropyl)amide 5-[((5-chloro-2-thienylmethyl)amino)- carbonyl]- pyridine-2-carboxylic acid.

Example 103

Ethylamide 5-[((2-thienylmethyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

Example 104

N-butylamide 5-[((2-thienylmethyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 105

(2-methoxyethyl)amide 5-[((8-chinaillon)amino)carbonyl] - pyridine-2-carboxylic acid

Example 106

(2-methoxyethyl)amide 5-[((4-[4,6-dichloro-4-Hina in accordance with example 3a) corresponding amines by the method in accordance with the present invention were obtained the following compounds (examples 107 and 108 in the original there).

Example 109

(2-methoxyethyl)amide 5-[((phenylsulfonyl)amino)carbonyl] -pyridine - 2-carboxylic acid. The pace. plvl. 190-191oC (after recrystallization from water).

Example 110

(Glycemically ester)amide 5-[((phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid. The pace. plvl. 125-126oC (after recrystallization from water).

Example 111

Glycolipid 5-[((phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid. The pace. plvl. 190-191oC (after recrystallization from water).

Example 112

(2-oxyethyl)amide 5-[((4-((2-phenylethyl)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

(a) Amide 4-((2-phenylethyl)aminocarbonyl)benzosulfimide acid.

of 20.1 g (0.1 mol) of amide 4-carboxymethycellulose acid are suspended in 300 ml of anhydrous tetrahydrofuran and, at 0oC, with stirring, was added to the resulting suspension is added dropwise to 15.2 ml (0.11 mol) of triethylamine. After 30 minutes, to the mixture was added dropwise at 0oC 10,5 ml (0.11 mol) of ethyl ether of Harborview acid, the mixture was stirred at this temperature for one hour, then cooled to -10oC and added to it dropwise to 12.1 g (0.1 mol, 12.5 ml) of 2-phenethylamine P>C, was evaporated in vacuum, the solid residue was treated with water have been pumped out, recrystallized from ethanol, receiving the result of 20.4 g of the product. The pace. plvl. 243-245oC.

b) Methyl ester 5-[((4-((2-phenylethyl)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

1.8 g (10 mmol) 2-methyl ester pyridine-2,5-dicarboxylic acid are suspended in 300 ml of anhydrous acetonitrile and mixing the mixture at 20oC when mixed with 3.0 g (10 mmol) of the above compounds, 2.1 g (10 mmol) of N,N'-dicyclohexylcarbodiimide and 1.2 g (10 mmol) 4-N, N-dimethylaminopyridine. The mixture was stirred at 20oC for 20 hours, then was filtered, nerastvorim residue, the filtrate was evaporated in vacuo, the residue was dissolved in 200 ml dichloromethane and twice was extracted with saturated aqueous NaHCO3and then with 100 ml of 2 n aqueous HCl. Drop down the crystalline residue was treated with warm methanol was aspirated and dried. The result was obtained 2.2 g of the target ester. The pace. plvl. 228-230oC.

c) the Target compound was obtained by reacting 0.8 g (1.7 mmol) of the above compound in 10 ml of 2-aminoethanol. The reaction was carried out at 80-90oC, pichette water and acidified solution with an aqueous solution of HCl to pH 1. The crystalline product was once again treated with ethyl acetate, was aspirated and dried. The result obtained 0.73 g of product as colorless crystals. The pace. plvl. 228-230oC.

Example 113

(2-oxyethyl)amide 5-[((4-benzylaminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 114

(2-oxyethyl)amide 5-[((4-((3-phenyl-n-propyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 115

(2-oxyethyl)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 116

(2-oxyethyl)amide 5-[((4-((2-(4-methoxyphenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 243-244oC (after recrystallization from water)

Example 117

(2-oxyethyl)amide 5-[((4-((2-(3,4-acid)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 201-203oC (after recrystallization from ethyl acetate).

Example 118

(2-oxyethyl)amide 5-[((4-((2-(2-methoxyphenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 119

(2 notes.

Example 120

(2-oxyethyl)amide 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 121

(2-oxyethyl)amide 5-[((4-(ethylaminomethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 122

(2-oxyethyl)amide 5-[((4-(N-butylaminoethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 245oC.

Example 123

(2-oxyethyl)amide 5-[((4-(n-mexiletineciclovir)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 124

5-[((4-(N, N-di-n-butylaminoethyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 125

(2-oxyethyl)amide 5-[((4-(cyclohexanecarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 126

(2-oxyethyl)amide 5-[((4-(2-methoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 127

(2-oxyethyl)amide 5-[((4-(2-ethoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 128

(2-oxyethyl)amide 5-[((4-(3-ethoxypropan)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-sulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 130

(2-oxyethyl)amide 5-[((3-(benzylaminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 131

(2-oxyethyl)amide 5-[((3-((3-phenylpropyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid

Example 132

(2-oxyethyl)amide 5-[((3-((4-phenyl-n-butyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 133

(2-ethoxyethyl)amide 5-[((3-((2-(4-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 134

(2-oxyethyl)amide 5-[((3-((2-(3,4-acid)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 135

(2-ethoxyethyl)amide 5-[((3-((2-(2-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 136

(2-ethoxyethyl)amide 5-[((3-((2-(4-forfinal)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 137

(2-ethoxyethyl)amide 5-[((3-((2-(4-chlorophenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 138

(2-ethoxyethyl)amide 5-[((3-(ethylaminomethyl)phenylenecarbonyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 140

(2-oxyethyl)amide 5-[((3-n-mexiletineciclovir)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 141

(2-ethoxyethyl)amide 5-[((3-(N,N-di-n-butylaminoethyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 142

(2-ethoxyethyl)amide 5-[((3-(cyclohexanecarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 143

5-[((3-((2-methoxyethyl)aminocarbonyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 144

(2-ethoxyethyl)amide 5-[((3-((2-ethoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 145

(2-ethoxyethyl)amide 5-[((3-((3-methoxypropyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 146

(2-ethoxyethyl)amide 5-[((3-((2-phenylethyl)aminocarbonyl) phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid. The pace. plvl. 189-191oC.

Example 147

(2-oxyethyl)amide 5-[((3-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 148

(2-methoxyethyl)amide 5-[((4-(benzylaminocarbonyl) sulfonylamino)carbonyl]-the l) phenylsulfonyl)amino)carbonyl]pyridine-2-carboxylic acid.

Example 150

(2-methoxyethyl)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 151

(2-methoxyethyl)amide 5-[((4-((2-(4-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 152

(2-methoxyethyl)amide 5-[((4-((2-(3,4-acid)ethyl) aminocarbonyl)phenoxycarbonyl)amino)carbonyl] -pyridine-2-carboxylic acid. The pace. plvl. 161-163oC (after recrystallization from ethyl acetate).

Example 153

(2-methoxyethyl)amide 5-[((4-((2-(2-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 154

(2-methoxyethyl)amide 5-[((4-((2-(4-forfinal)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 155

(2-methoxyethyl)amide 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 156

(2-methoxyethyl)amide 5-[((4-ethylaminomethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 157

(2-methoxyethyl)amide 5-[((4-(n-butylaminoethyl)phenylsulfonyl) amino)carbonyl]- pyridine-2-carbon is arbonyl]-pyridine-2-pyridine-2-carboxylic acid.

Example 159

(2-methoxyethyl)amide 5-[((4-(N, N-di-n-butylaminoethyl) phenylsulfonyl)amino)carboxyl]-pyridine-2-carboxylic acid.

Example 160

(2-methoxyethyl)amide 5-[((4-(cyclohexanecarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 161

(2-methoxyethyl)amide 5-[((4-((2-methoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 162

(2-methoxyethyl)amide 5-[((4-((2-ethoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 163

(2-methoxyethyl)amide 5-[((4-((3-ethoxypropan)aminocarbonyl)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 164

(2-methoxyethyl)amide 5-[((4-((2-phenylethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 165

(2-methoxyethyl)amide 5-[((4-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 166

(2-methoxyethyl)amide 5-[((3-(benzylaminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 167

(2-methoxyethyl)amide 5-[((3-((phenylpropyl) aminocarbonyl)peninsul-butyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 169

(2-methoxyethyl)amide 5-[((3-((2-(3,4-acid)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 170

(2-methoxyethyl)amide 5-[((3-((2-(3-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 171

(2-methoxyethyl)amide 5-[((3-((2-(2-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 172

(2-methoxyethyl)amide 5-[((3-((2-(4-forfinal)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 173

(2-methoxyethyl)amide 5-[((3-((2-(4-chlorophenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 174

(2-methoxyethyl)amide 5-[((3-(ethylaminomethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 175

(2-methoxyethyl)amide 5-[((3-(n-butylaminoethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 176

(2-methoxyethyl)amide 5-[((3-(n-mexiletineciclovir) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 177

(2-methoxyethyl)amide 5-[((3-(N, N-di-n-butyl is setil)amide 5-[((3-(cyclohexanecarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 179

(2-methoxyethyl)amide 5-[((3-((2-methoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 180

(2-methoxyethyl)amide 5-[((3-((2-ethoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 181

(2-methoxyethyl)amide 5-[((3-((3-methoxypropyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 182

(2-methoxyethyl)amide 5-[((3-((2-phenylethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 183

(2-methoxyethyl)amide 5-[((3-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 184

(2-methoxyethyl)amide 5-[((4-(benzylaminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 185

(2-ethoxyethyl)amide 5-[((4-(3-phenylpropyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 186

(2-ethoxyethyl)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 187

(2-ethoxyethyl)amide 5-[((4-((2-(4-methoxyphenyl)ethyl)aminocarbonyl f is(2-(3,4-acid)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 189

(2-ethoxyethyl)amide 5-[((4-((2-(2-methoxyphenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 190

(2-ethoxyethyl)amide 5-[((4-((2-(4-forfinal)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 191

(2-ethoxyethyl)amide 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 192

(2-ethoxyethyl)amide 5-[(((4-ethylaminomethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 193

(2-accosiated)amide 5-[((4-(n-butylaminoethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 194

(2-accosiated)amide 5-[((4-(n-mexiletineciclovir) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 195

(2-accosiated)amide 5-[((4-(N, N-di-n-butylaminoethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 196

(2-accosiated)amide 5-[((4-(cyclohexanecarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 197

(2-accosiated)amide 5-[((4-((2-methoxyethyl)aminocarbonyl) phenylsulfonyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 199

(2-accosiated)amide 5-[((4-((3-ethoxypropan)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 200

(2-ethoxyethyl)amide 5-[((4-((2-phenylethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 201

(2-ethoxyethyl)amide 5-[((4-((2-phenoxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 202

Sodium salt (glycemically ester)amide 5-[((4-((2-phenylethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

and) 5-[((4-((2-phenylethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid

0.7 g (1.5 mmol) described in example 112b) methyl ester contribute at 20oC under stirring in 100 ml of 1.5 n methanolic NaOH solution. After the formation of a solution from it later precipitation of the crystalline product. Stirring is continued for another 30 minutes. After that, the mixture is evaporated in vacuo, the residue is dissolved in a mixture of water and tetrahydrofuran (THF, acidified with a solution of aqueous HCl solution to pH 1, it evaporated in a vacuum and suck colorless crystalline product. The result is 0.6 g soedinenie pyridine-2-carboxylic acid are suspended in 200 ml of anhydrous mixture of acetonitrile and tetrahydrofuran, successively added thereto 0.7 g (5.5 mmol) of the hydrochloride licensedialog ether, 1,4 ml (11 mmol) of N-ethylmorpholine, 0,73 (5.5 mmol) of 1-oxibendazole and 1.14 g (5.5 mmol) of N,N'-dicyclohexylcarbodiimide and stirred the whole mixture for 20 hours at 20oC. the insoluble residue is filtered off, the filtrate is evaporated in vacuo, the residue is dissolved in 200 ml of dichloromethane and the extraction is carried out twice with a saturated aqueous solution of NaHCO3. Of NaHCO3-phase by crystallization obtain 0.75 g of the product. The pace. plvl. 275 - 277oC. From the organic phase after drying, evaporation and treatment of the residue with ethyl acetate get more of 0.42 g of colorless crystal product. The pace. plvl. 275 - 277oC (with foaming).

Example 203

(Glycemically ester)amide 5-[((4-(benzylaminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 204

(Glycemically ester)amide 5-[((4-((3-phenylpropyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 205

(Glycemically ester)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 206

(Glycymeris the acid.

Example 207

Sodium salt (glycemically ester) amide 5-[((4-((2-(3,4- acid)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

The pace. plvl. 190 - 191oC (after recrystallization from methanol).

Example 208

(Glycemically ester) amide 5-[((4-((2-(2-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 209

2-(glycemically ester) amide 5-[((4-((2-(4-forfinal)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 210

(Glycemically ester) amide 5-[((4-((2-(4-chlorophenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 211

(Glycemically ester)amide 5-[((4-(ethylaminomethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 212

(Glycemically ester)amide 5-[((4-(n-butylaminoethyl) phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid Temp. plvl. 215 - 217oC (after recrystallization from methanol).

Example 213

(Glycemically ester)amide 5-[((4-(n-mexiletineciclovir) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic key is Mino)carbonyl]-pyridine-2-carboxylic acid.

Example 215

(Glycemically ester)amide 5-[((4-(cyclohexanecarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 216

(Glycemically ester)amide 5-[((4-((2-methoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 217

(Glycemically ester)amide 5-[((4-((2-ethoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 218

(Glycemically ester)amide 5-[((4-((3-ethoxypropan)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 171 - 173oC (after recrystallization from methanol).

Example 219

(Glycemically ester)amide 5-[((4-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 220

(Glycemically ester)amide 5-[((3-(benzylaminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 221

(Glycemically ester)amide 5-[((3-((3-phenylpropyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 222

(Glycemically ester)amide 5-[((3-((4-phenyl-n-butyl)aminocarbonyl) phenyl� 5-[((3-((2-(4-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 224

(Glycemically ester)amide 5-[((3-((2-(3-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 225

(Glycemically ester)amide 5-[((3-((2-(2-methoxyphenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 226

2-(glycemically ester)amide 5-[((3-((2-(4-forfinal)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 227

(Glycemically ester)amide 5-[((3-((2-(4-chlorophenyl)ethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 228

(Glycemically ester)amide 5-[((3-(ethylaminomethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 229

(Glycemically ether) 5-[((3-(n-butylaminoethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 198 - 200oC (after recrystallization from methanol).

Example 230

(Glycemically ester)amide 5[((3-(n-mexiletineciclovir) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 231

(Glycemically ester)amide 5-[((3-(N,N-di-n-butylaminoethyl)amide 5-[((3-(cyclohexanecarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 233

(Glycemically ester)amide 5-[((3-((2-methoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 234

(Glycemically ester)amide 5-[((3-((2-ethoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 235

(Glycemically ester)amide 5-[((3-((3-ethoxypropan)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 236

(Glycemically ester)amide 5-[((3-((2-phenylethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 237

(Glycemically ester)amide 5-[((3-((-phenoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 238

(Glycemically ester)amide 5-[((4-(benzylaminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 239

(Glycylation ester)amide 5-[((4-((3-phenylpropyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 240

(Glycylation ester)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 241

Example 242

(Glycylation ester)amide 5-[((4-((2-(3,4-acid)ethyl)aminocarbonyl)phenylsulfonyl)amino) carbonyl] -pricin-2-carboxylic acid.

Example 243

(Glycylation ester)amide 5-[((4-((2-(2-methoxyphenyl)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 244

(Glycylation ester)amide 5-[((4-((2-(4-forfinal)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 245

(Glycylation ester)amide 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 246

(Glycylation ester)amide 5-[((4-(ethylaminomethyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 247

(Glycylation ester)amide 5-[((4-(n-butylaminoethyl)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 248

(Glycylation ester)amide 5-[((4-(n-mexiletineciclovir)phenylsulfonyl)amino)carbonyl]-pricin-2-carboxylic acid.

Example 249

(Glycylation ester)amide 5-[((4-(N,N-di-n-butylaminoethyl)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example benovoy acid.

Example 251

(Glycylation ester)amide 5-[((4-((2-methoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 252

(Glycylation ester)amide 5-[((4-((2-ethoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 253

(Glycylation ester)amide 5-[((4-((3-ethoxypropan)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 254

(Glycylation ester)amide 5-[((4-((2-phenylethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 255

(Glycylation ester)amide 5-[((4-((2-phenoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

Example 256

(Glycyl-2-propyl ester)amide 5-[((4-(benzylaminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

Example 257

(Glycyl-2-propyl ester)amide 5-[((4-(3-phenylpropyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

Example 258

(Glycyl-2-propyl ester)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Pronil] -pyridine-2-carboxylic acid.

Example 260

(Glycyl-2-propyl ester)amide 5-[((4-((2-(3,4-acid)ethyl)aminocarbonyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 261

(Glycyl-2-propyl ester)amide 5-[((4-((2-(2-methoxyphenyl)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 262

(Glycyl-2-propyl ester)amide 5-[((4-((2-(4-forfinal)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 263

(Glycyl-2-propyl ester)amide 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 264

(Glycyl-2-propyl ester)amide 5-[((4-(ethylaminomethyl)phenylsulfonyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

Example 265

(Glycyl-2-propyl ester)amide 5-[((4-(n-butylaminoethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 266

(Glycyl-2-propyl ester)amide 5-[((4-(n-mexiletineciclovir)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 267

(Glycyl-2-propyl ester)amide 5-[((4-(N, N-di-n-butylaminoethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carbonothioyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 269

(Glycyl-2-propyl ester)amide 5-[((4-((2-methoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 270

(Glycyl-2-propyl ester)amide 5-[((4-((2-ethoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 271

(Glycyl-2-propyl ester)amide 5-[((4-((3-ethoxypropan)-aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 272

(Glycyl-2-propyl ester)amide 5-[((4-((2-phenylethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 273

(Glycyl-2-propyl ester)amide 5-[((4-((2-phenoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 274

(Pitilessly ester)amide 5-[((4-(benzylaminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 275

(Pitilessly ether) 5-[((4-((3-phenylpropyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

Example 276

(Pitilessly ester)amide 5-[((4-((4-phenyl-n-butyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid.

which of IMT] -pyridine-2-carboxylic acid.

Example 278

(Pitilessly ester)amide 5-[((4-((2-(3,4-acid)ethyl)aminocarbonyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 279

(Pitilessly ester)amide 5-[((4-((2-(2-methoxyphenyl)ethyl)- aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 280

2-(pitilessly ester)amide 5-[((4-((2-(4-forfinal)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 281

(Pitilessly ester)amide 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 282

(Pitilessly ester)amide 5-[((4-(ethylaminomethyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 283

(Pitilessly ester)amide 5-[((4-(n-butylaminoethyl)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 284

(Pitilessly ester)amide 5-[((4-(n-mexiletineciclovir)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 285

(Pitilessly ester)amide 5-[((4-(N,N-di-n-butylaminoethyl)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid)carbonyl] - pyridine-2-carboxylic acid.

Example 287

(Pitilessly ester)amide 5-[((4-((2-methoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 288

(Pitilessly ester)amide 5-[((4-(2-ecosites)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 289

(Pitilessly ester)amide 5-[((4-((3-ethoxypropan)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 290

(Pitilessly ester)amide 5-[((4-((2-phenylethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 291

(Pitilessly ester)amide 5-[((4-((2-phenoxyethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 292

Glycolipid 5-[((3-(n-butylaminoethyl)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

The pace. the melt. 220 - 230oC (after recrystallization from aqueous hydrochloric acid).

Example 293

Glycolipid 5-[((4-(3-phenylpropyl)aminocarbonyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 294

Glycolipid 5[((4-(4-phenyl-n-butyl)lamed 5-[((4-((2-(-4-methoxyphenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carbonepoxy acid.

Example 296

Glycolipid 5-[((4-((2-(3,4-acid)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid. The pace. the melt. 190oC (sintering), 201 - 203oC (after recrystallization from aqueous hydrochloric acid).

Example 297

Glycolipid 5-[((4-((2-(2-methoxyphenyl)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 298

2-glycinamide 5-[((4-((2-(4-forfinal)ethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 299

Glycolipid 5-[((4-((2-(4-chlorophenyl)ethyl)aminocarbonyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 300

Glycolipid 5-[((4-(ethylaminomethyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 301

Glycolipid 5-[((4-(n-butylaminoethyl)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 244 - 247oC (with decomposition, after recrystallization from aqueous hydrochloric acid).

Example 302

Glycolipid 5-[((4-(n-mexiletineciclovir)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 303

Glycolipid 5-[((4304

Glycolipid 5-[((4-cyclohexanecarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 305

Glycolipid 5-[((4-((2-methoxyethyl)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 306

Glycolipid 5-[((4-((2-ethoxyethyl)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 307

Glycolipid 5-[((4-(3-ethoxypropan)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 190oC (after recrystallization from a mixture of tetrahydrofuran and an aqueous solution of hydrochloric acid).

Example 308

Glycolipid 5-[((4-((2-phenylethyl)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 263 - 265oC (after recrystallization from aqueous hydrochloric acid).

Example 309

Glycolipid 5-[((4-((2-phenoxyethyl)aminocarbonyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 310

(2-oxyethyl)amide 5-[((2-chloro-4-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 311

(2-oxyethyl)amide 5-[((2-chloro-4-(3-BR>
(2-oxyethyl)amide 5-[((4-chloro-3-((3-ethoxypropan)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 313

(2-oxyethyl)amide 5-[((4-chloro-3-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 314

(2-methoxyethyl)amide 5-[((2-chloro-4-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 315

(2-methoxyethyl)amide 5-[((2-chloro-4-(3-ethoxypropan)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 316

(2-methoxyethyl)amide 5-[((4-chloro-3-((3-ethoxypropan)aminocarbonyl)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 317

(2-methoxyethyl)amide 5[((4-chloro-3-((2-phenoxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 318

(2-ethoxyethyl)amide 5[((2-chloro-4-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 319

(Ethoxyethyl)amide 5[((2-chloro-4-((3-ethoxypropan)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 320

(2-ethoxyethyl)amide 5[((4-chloor 321

(2-ethoxyethyl)amide 5[((4-chloro-3-((2-phenoxyethyl)aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 322

(2-(2-propyl)oxyethyl)amide 5[((2-chloro-4-((2-phenoxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 323

(2-(2-propyl)oxyethyl)amide 5-[((2-chloro-4-((3-ethoxypropan) aminocarbonyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 324

(Glycemically ester)amide 5-[((2-chloro-4-((2-phenoxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 325

(Glycemically ester)amide 5-[((2-chloro-4-((3-ethoxypropan) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 326

(Glycemically ester)amide 5-[((4-chloro-3-((3-ethoxypropan) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 327

(Glycemically ester)amide 5-[((4-chloro-3-((2-phenoxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 328

(Glycyl-2-propyl ester)amide 5-[((2-chloro-4-((2-phenoxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carbon is phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 330

(Glycyl-3-phenyl ether)amide 5-[((2-chloro-4-((2-vinyloxyethyl) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 331

(glycyl-3-phenyl ether)amide 5-[((2-chloro-4-((3-ethoxypropan) aminocarbonyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 332

(2-oxyethyl)amide 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino) ethyl)aminocarbonyl)phenylsulfonyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

a) Methyl ester 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Retrieved from 4.0 g ((22 mmol) 2-methyl ester pyridine-2,5-dicarboxylic acid thus, as described in example 1c), the acid chloride 5-carboxylic acid methyl ester pyridine-2-carboxylic acid in 50 ml of anhydrous 1,4 - dioxane was added at 40oC to the reaction mixture, consisting of the 7.4 g (20 mmol) of amide 2-(((2-chloro-5-methoxybenzoyl)amino)ethyl) - benzosulfimide acid (obtained from amide 4-(2-amino-ethyl)benzosulfimide acid and 2-chloro-5-methoxybenzoic acid), 2.3 g (20 mmol) of trebuchet potassium in 150 ml of anhydrous 1,4-dioxane (for the formation of sodium salt sulfonamida assests the ut at 60oC, and then boiled for 2 hours under reflux, after which the solvent is kept in vacuum, the residue was dissolved in water, the solution was acidified with an aqueous solution of HCl to pH 1 to 2 and perform the extraction with dichloromethane. The residue was treated with hot ethyl acetate, was aspirated and washed with ethyl acetate. Thus obtained crude product (2.8 g) was treated with 100 ml of cold, then 100 ml of hot water was aspirated and the colorless crystalline product. The output of 2.6, Temp.plvl. 187 - 190oC

b) 0,85 g obtained as described above methyl ester was stirred for one hour at 80 - 90oC in 150 ml of 2-aminoethanol. After cooling, the excess reagent is kept in vacuum, the residue was dissolved in 20 to 30 ml of water, acidified with concentrated aqueous HCl solution to pH 1, was aspirated crystalline product was washed with water, and treated with hot ethyl acetate and again sucked out. The result was obtained 0.65 g of the target compound. The pace. plvl. 135 - 137oC.

Example 333

(2-oxyethyl)amide 5-[((4-(2-(acetylamino)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 334

(2-oxyethyl)amide 5-[((4-(2-(n-butanediamine)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carbonateitamin-2-carboxylic acid.

Example 336

(2-oxyethyl)amide 5-[((4-(2-((4-chlorobenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 337

(2-oxyethyl)amide 5-[((4-(2-((5-chloro-2-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 338

(2-oxyethyl)amide 5-[((4-(2-((3-3,4-dimethoxyphosphinyl) amino)ethyl)phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid. The pace. plvl. 176 - 177oC (after recrystallization from water).

Example 339

(2-oxyethyl)amide 5-[((4-(2-((2-phenylacetyl)amino)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 340

(4-oxyethyl)amide 5-[((4-(2-((phenoxyacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid. The pace. plvl. 155 - 156oC (after recrystallization from water).

Example 341

(2-oxyethyl)amide 5-[((4-(2-((4-perbenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 342

(2-oxyethyl)amide 5-[((4-(2-((4-methylpentanol)amino)ethyl) phenylsulfonyl)amino)carbonyl] -pyridine-2-carboxylic acid. The pace. plvl. 179 - 181oC (after recrystallization from water).

Example 343

(2-oxyethyl)amide 5-Mer 344

(2-oxyethyl)amide 5-[((4-(2-((cyclohexylmethyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 345

(2-oxyethyl)amide 5-[((4-(2-((2-methylpropionyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 346

(2-oxyethyl)amide 5-[((3-(2-((2-chloro-5-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 347

(2-oxyethyl)amide 5-[((3-(2-acetylamino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 348

(2-oxyethyl)amide 5-[((3-(2-(n-butanamine(ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 349

(2-oxyethyl)amide 5-[((3-(2-(benzoylamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 350

(2-oxyethyl)amide 5-[((3-(2-((4-chlorobenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 351

(2-oxyethyl)amide 5-[((3-(2-((5-chloro-2-methoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 352

(2-oxyethyl)amide 5-[((3-(2-((3-phenyl-n-propionyl)amino)ethyl)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carbon is)carbonyl]-pyridine-2-carboxylic acid.

Example 354

(2-oxyethyl)amide 5-[((3-(2-((phenoxyacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 355

(2-oxyethyl)amide 5-[((3-(2-((4-perbenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 356

(2-oxyethyl)amide 5-[((3-(2-((4-ethoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 357

(2-oxyethyl)amide 5-[((3-(2-((cyclohexanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 358

(2-oxyethyl)amide 5-[((3-(2-((cyclohexylmethyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 359

(2-oxyethyl)amide 5-[((3-(2-((2-methylpropionyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 360

(2-methoxyethyl)amide 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 361

(2-methoxyethyl)amide 5-[((4-(2-(acetylamino)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 362

(2-methoxyethyl)amide 5-[((4-(2-(n-butanolate)ethyl)phenylsulfonyl) amino)kernelcolonel) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 364

(2-methoxyethyl)amide 5-[((4-(2-((4-chlorobenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 365

(2-methoxyethyl)amide 5-[((4-(2-((5-chloro-2-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 366

(2-methoxyethyl)amide 5-[((4-(2-((3-(3,4-acid)propionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 87-89oC (amorphous substance, after recrystallization from diisopropyl ether).

Example 367

(2-methoxyethyl)amide 5-[((4-(2-((2-phenylacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 368

(2-methoxyethyl)amide 5-[((4-(2-((phenoxyacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 369

(2-methoxyethyl)amide 5-[((4-(2-((4-perbenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 370

(2-methoxyethyl)amide 5-[((4-(2-((4-methylpentanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 154-157oC (after recrystallization from water).

Example 371

Example 372

(2-methoxyethyl)amide 5-[((4-(2-((cyclohexylmethyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 373

(2-methoxyethyl)amide 5-[((4-(2-((2-methylpropionyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 374

(2-methoxyethyl)amide 5-[((3-(2-((2-chloro-5-methoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 375

(2-methoxyethyl)amide 5-[((3-(2-(acetylamino)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 376

(2-methoxyethyl)amide 5-[((3-(2-(n-butanolate)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 377

(2-methoxyethyl)amide 5-[((3-(2-(benzoylamine)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 378

(2-methoxyethyl)amide 5-[((3-(2-((4-chlorobenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 379

(2-methoxyethyl)amide 5-[((3-(2-((5-chloro-2-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 380

(2-methoxyethyl)amide 5-[((3-(2-((3-phenyl-n-propionyl)amino)ethyl) - Hairdryer-((2-phenylacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 382

(2-methoxyethyl)amide 5-[((3-(2-((phenoxyacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 383

(2-methoxyethyl)amide 5-[((3-(2-((4-perbenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 384

(2-methoxyethyl)amide 5-[((3-(2-((4-ethoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 385

(2-methoxyethyl)amide 5-[((3-(2-((cyclohexanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 386

(2-methoxyethyl)amide 5-[((3-(2-((cyclohexylmethyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 387

(2-methoxyethyl)amide 5-[((3-(2-((2-methylpropionyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 388

(2-methoxyethyl)amide 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 389

(2-methoxyethyl)amide 5-[((4-(2-(acetylamino)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 390

(2-methoxyethyl)amide 5-[((4-(2-(n-butanolate)ethyl)panels is solumina)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 392

(2-methoxyethyl)amide 5-[((4-(2-((4-chlorobenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 393

(2-methoxyethyl)amide 5-[((4-(2-((5-chloro-2-methoxybenzoyl)amino)- ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 394

(2-methoxyethyl)amide 5-[((4-(2-((3-phenyl-n-propionyl)amino)- ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 395

((2-methoxyethyl)amide 5-[((4-(2-((2-phenylacetyl)amino)ethyl - phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 396

(2-methoxyethyl)amide 5-[((4-(2-((phenoxyacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 397

(2-methoxyethyl)amide 5-[((4-(2-((4-perbenzoic)amine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 398

(2-methoxyethyl)amide 5-[((4-(2-((4-ethoxybenzoyl)amino)ethyl)) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 399

(2-methoxyethyl)amide 5-[((4-(2-((cyclohexanol)aminoethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 400

(2-methoxyethyl)amide 5-[((4-(2-((cyclohexylethyl)amine is)amide 5-[((4-(2-((2-methylpropionyl)amino)ethyl)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 402

(2-acetoxyethyl)amide 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 403

(2-acetoxyethyl)amide 5-[((4-(2-(acetylamino)ethyl)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 404

(2-acetoxyethyl)amide 5-[((4-(2-(n-butanolate)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 405

(2-acetoxyethyl)amide 5-[((4-(2-(benzoylamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 406

(2-acetoxyethyl)amide 5-[((4-(2-((4-chlorobenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 407

(2-acetoxyethyl)amide 5-[((4-(2-((5-chloro-2-methoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 408

(2-acetoxyethyl)amide 5-[((4-(2-((3-phenyl-n-propionyl)amino)- ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 409

(2-acetoxyethyl)amide 5-[((4-(2-((2-phenylacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 410

(2-acetoxyethyl)amide 5-[((4-(2-((phenoxyacetyl)amino)ethyl) -[((4-(2-((4-perbenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 412

(2-acetoxyethyl)amide 5-[((4-(2-((4-ethoxybenzoyl)amino)ethyl)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 413

(2-acetoxyethyl)amide 5-[((4-(2-((cyclohexanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 414

(2-acetoxyethyl)amide 5-[((4-(2-((cyclohexylmethyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 415

(2-acetoxyethyl)amide 5-[((4-(2-((2-methylpropionyl)amino)ethyl)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 416

(2-(2-methylbenzoyl)oxyethyl)amide 5-[((4-(2-((2-chloro-5 - methoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 417

(2-(2-methylbenzoyl(oxyethyl)amide 5-[((4-(2-(acetylamino)ethyl)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 418

(2-(2-methylbenzoyl)oxyethyl)amide 5-[((4-(2-(n-butanolate)- ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 419

(2-(2-methylbenzoyl)oxyethyl)amide 5-[((4-(2-(benzoylamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 420

(2-(2-metalloy.

Example 421

(2-(2-methylbenzoyl)oxyethyl)amide 5-[((4-(2-((5-chloro-2 - methoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 422

(2-(2-methylbenzoyl)oxyethyl)amide 5-[((4-(2-((3-phenyl-n - propionyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 423

(2-(2-methylpropionyl)oxyethyl)amide 5-[((4-(2-((2-phenylacetyl)- amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 424

(2-(2-methylpropionyl)oxyethyl)amide 5-[((4-(2-(phenoxyacetyl)- amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 425

(2-(2-methylpropionyl)oxyethyl)amide 5-[((4-(2-((4-perbenzoic)- amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 426

(2-(2-methylpropionyl)oxyethyl)amide 5-[((4-(2- ((4-ethoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine - 2-carboxylic acid.

Example 427

(2-(2-methylpropionyl)oxyethyl)amide 5-[((4-(2-((cyclohexanol)- amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 428

(2-(2-methylpropionyl)oxyethyl)amide 5-[((4-(2- ((cyclohexylmethyl)amino)ethyl)phenylsulfonyl)AMI((2 - methylpropionyl)-amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 430

(2-oxyethyl)amide 5-[((4-(2-((2-ethylbutanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 431

(2-methoxyethyl)amide 5-[((4-(2-((2-ethylbutanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 432

(2-oxyethyl)amide 5-[((4-(2-((4-n-butoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 433

(Glycemically ester)amide 5-[((4-(2-((2-chloro-5-methoxybenzoyl)- amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

a) 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

0.8 g (of 1.36 mmol) of the methyl ester from example 332a) omilami in the same manner as described in example 202a), 30 ml of 1 n methanolic NaOH solution. After evaporation in vacuo the residue was dissolved in tetrahydrofuran, the solution was acidified aqueous HCl was evaporated, the residue was treated with water and was sucked out. The result was allocated 0.75 g of the target product. The pace. plvl. 149oC (decomposition).

b) 0.7 g (1.35 mmol) obtained in this way is derived pyridine-2-carboxylic acid in 100 ml of anhydrous acetonitrile that is delovogo ether, 0.4 ml (3 mmol) of N-ethylmorpholine, 0.33 g (1.5 mmol) of 1-oxibendazole and 0.31 g (1.5 mmol) of N,N'-dicyclohexylcarbodiimide.

Then, the insoluble residue was filtered, the filtrate was evaporated, the residue was dissolved in 1,4-dioxane, the resulting solution was acidified with 2 n aqueous HCl solution and it was evaporated in vacuum. The crystalline product was aspirated, washed and dried. The obtained crude product was subjected to purification using chromatography on silica gel, using as mobile phase a mixture of dichloromethane and methanol in a ratio of 19:1. The appropriate fractions were evaporated, the residue was recrystallized from hot methanol, crystalline product was aspirated, washed with methanol and dried. The result was obtained 0.51 g of target compound in the form of colorless crystalline material. The pace. plvl. 192-194oC.

Example 434

(Glycemically ester)amide 5-[((4-(2-(acetylamino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 435

(Glycemically ester)amide 5-[((4-(2-n-hexanamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 128-130oC (after recrystallization from ethyl acetate).

The use of the OIC acid.

Example 437

(Glycemically ester)amide 5-[((4-(2-((4-chlorobenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 438

(Glycemically ester)amide 5-[((4-(2-((3,4-acid) propionyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid

The pace. plvl. 139-141oC (after chromatography on silica gel using as mobile phase a mixture of ethyl acetate and methanol in the ratio 9:1).

Example 439

(glycemically ester)amide 5-[((4-(2-((3-phenyl-n-propionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid

Example 440

(glycemically ester)amide 5-[((4-(2-((2-phenylacetyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 441

(Glycemically ester)amide 5-[((4-(2-((phenoxyethyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 442

(Glycemically ester)amide 5-[((4-(2-((4-perbenzoic)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 443

(Glycylation ester)amide 5-[((4-(2-((3,4-diethoxybenzoic) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 445

(Glycemically ester)amide 5-[((4-(2-((cyclohexylmethyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 178-179oC (after recrystallization from a mixture of methanol and diisopropyl ether).

Example 446

(Glycemically ester)amide 5-[((4-(2-((2-methylpropionyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 197-199oC (after chromatographic separation on silica gel using as mobile phase a mixture of ethyl acetate and methanol in the ratio 9:1).

Example 447

(Glycemically ester)amide 5-[((4-(2-(4-methylpentanol)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 160-162oC (after chromatographic purification on silica gel using as mobile phase a mixture of ethyl acetate and methanol).

Example 448

(Glycyl-2-propyl ester)amide 5-[((4-(2-((2-chloro-5 - methoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 449

(Glycyl-2-propyl ester)amide 5-[((4-(2-(acetylamino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 451

(Glycyl-2-propyl ester)amide 5-[((4-(2-(benzoylamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 452

(Glycine-2-propyl ester)amide 5-[((4-(2-((4-chlorobenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 453

(Glycyl-2-propyl ester)amide 5-[((4-(2-((5-chloro-2 - methoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 454

(Glycyl-2-propyl ester)amide 5-[((4-(2-((3-phenyl-n-propionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 455

(Glycyl-2-propyl ester)amide 5-[((4-(2-((2-phenylacetyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 456

(Glycyl-2-propyl ester)amide 5-[((4-(2-((phenoxyacetyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 457

(Glycyl-2-propyl ester)amide 5-[((4-(2-((4-perbenzoic)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 458

(Glycyl-2-propyl ester)amide 5-[((4-(2-((4-ethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic sour is)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 460

(Glycyl-2-propyl ester)amide 5-[((4-(2-((cyclohexylmethyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 461

(Glycyl-2-propyl ester)amide 5-[((4-(2-(2-methylpropionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 462

(Glycyl-2-propyl ester)amide 5-[((4-(2-(2-ethylbutanol)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 463

(Pitilessly ester)amide 5-[((4-(2-((2-chloro-5 - methoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 464

(Pitilessly ester)amide 5-[((4-(2-(acetylamino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 465

(Pitilessly ester)amide 5-[((4-(2-(n-butanolate)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 466

(Pitilessly ester)amide 5-[((4-(2-(benzoylamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 467

(Pitilessly ether) 5-[((4-(2-((4-chlorobenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 468 ridin-2 - carboxylic acid.

Example 469

(Pitilessly ester)amide 5-[((4-(2-((3-phenyl-n-propionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 470

(Pitilessly ester)amide 5-[((4-(2-((2-phenylacetyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 471

(Pitilessly ester)amide 5-[((4-(2-((4-perbenzoic)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 472

(Pitilessly ester)amide 5-[((4-(2-((4-perbenzoic)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 473

(Pitilessly ester)amide 5-[((4-(2-((4-ethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 474

(Pitilessly ester)amide 5-[((4-(2-((cyclohexanol)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 475

(Pitilessly ester)amide 5-[((4-(2-((cyclohexylmethyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 476

(Pitilessly ester)amide 5-[((4-(2-(2-methylpropionyl)amine) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 478

Glycolipid 5-[((4-(2-((2-chloro-5-methoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 479

Glycolipid 5-[((4-(2-(acetylamino)ethyl)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 480

Glycolipid 5-[((4-(2-(n-hexanamine)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 115-116oC (after recrystallization from a mixture of tetrahydrofuran and an aqueous solution of hydrochloric acid).

Example 481

Glycolipid 5-[((4-(2-(benzoylamine)ethyl)phenylsulfonyl) amino)carbonyl] -pyridine-2-carboxylic acid.

Example 482

Glycolipid 5-[((4-(2-((4-chlorobenzoyl)amino)ethyl)phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 483

Glycolipid 5-[((4-(2-((3,4-dimethoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 484

Glycolipid 5-[((4-(2-((3-phenyl-n-propionyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 485

Glycolipid 5-[((4-(2-((2-phenylacetyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 486

Example 487

Glycolipid 5-[((4-(2-((4-perbenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 488

Glycolipid 5-[((4-(2-((3,4-diethoxybenzoic)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. above 230oC (after recrystallization from aqueous hydrochloric acid).

Example 489

Glycolipid 5-[((4-(2-((cyclohexanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 490

Glycolipid 5-[((4-(2-((cyclohexylmethyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 154-156oC (after recrystallization from aqueous hydrochloric acid).

Example 491

Glycolipid 5-[((4-(2-(2-methylpropionyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 269-271oC (after recrystallization from aqueous hydrochloric acid).

Example 492

Glycolipid 5-[((4-(2-(4-methylpentanol)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

The pace. plvl. 126-128oC (after recrystallization from aqueous hydrochloric kilfoil)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 494

(Glycemically ester)amide 5-[((3-(2-(acetylamino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 495

(Glycemically ester)amide 5-[((3-(2-(n-butanolate)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 496

(Glycemically ester)amide 5-[((3-(2-(benzoylamine)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 497

(Glycemically ester)amide 5-[((3-(2-((4-chlorobenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 498

(Glycemically ester)amide 5-[((3-(2-((5-chloro-2 - methoxybenzoyl)amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 499

(Glycemically ester)amide 5-[((3-(2-((3-phenyl-n-propionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2 - carboxylic acid.

Example 500

(Glycemically ester)amide 5-[((3-(2-((3-phenylacetyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 501

(Glycemically ester)amide 5-[((4-(3-(2-((phenoxyacetyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 502

(CH is islote.

Example 503

(Glycemically ester)amide 5-[((3-(2-((4-ethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 504

(Glycemically ester)amide 5-[((3-(2-((cyclohexanol) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 505

(Glycemically ester)amide 5-[((3-(2-((cyclohexylmethyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 506

(Glycemically ester)amide 5-[((3-(2-(2-methylpropionyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 507

(Glycemically ester)amide 5-[((3-(2-(2-ethylbutanol) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 508

(2-oxyethyl)amide 5-[((4-((4-phenyl-n-butanoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

(a) Amide 4-((phenyl-n-butanoyl)amino)benzosulfimide acid.

16.5 g (0.1 mol) of 4-phenylalkanoic acid in 300 ml of anhydrous tetrahydrofuran were mixed at 0oC 11.1 g (0.11 mol, of 15.2 ml) of triethylamine. After 30 minutes, to the mixture was added dropwise at 0oC 12 g (0.11 mol, 10,5 ml) of the ethyl ether of Harborview to the sulfonamida in 150 ml of anhydrous tetrahydrofuran. The mixture was stirred for one hour at 0oC, and then for a further hour at 25oC, after which it was evaporated in vacuum and the residue was treated with an aqueous solution of hydrochloric acid. The crystalline crude product is washed with water and recrystallized from 250 ml of methanol. Exit 18, Temp. plvl. 166-168oC.

b) Methyl ester 5-[((4-((4-phenyl-n-butanoyl)amino)- phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

In the same manner as described in example 112b), 1.8 g (10 mmol) of methyl ester of pyridine-2,5-dicarboxylic acid in 300 ml of acetonitrile was subjected to interaction with 3.2 g (10 mmol) obtained in the above image benzosulfimide, 2.1 g (10 mmol) of N,N'-dicylopentadiene and 1.2 g (10 mmol) 4-N, N-dimethylaminopyridine. The insoluble residue was filtered, the filtrate was evaporated, mixed with an aqueous solution of hydrochloric acid (pH 1) was aspirated and the crystalline product. The latter was dissolved in N,N-dimethylformamide and mixed with water prior to the dimness. The crystalline crude product is washed with water and dried. Output 3.3V, Temp. plvl.258-264oC.

After chromatographic purification on silica gel using as mobile phase a mixture of etelaat. The result was obtained 1.4 g of colorless crystal product. The pace.plvl. 258oC (decomposition).

c) the Target compound was obtained, mixing 0.3 g (of 0.62 mmol) obtained as described above methyl ester in 5 ml of 2-aminoethanol for 2 hours at 80oC. the Excess reagent is kept in vacuum, the residue was dissolved and a small amount of tetrahydrofuran, the solution was acidified using 2 n aqueous solution of HCl, it was evaporated in vacuo, the crystalline residue was aspirated, washed with water and dried. The result was obtained 0.21 g of the target compound. The pace.plvl. 278-280oC.

Example 509

(2-oxyethyl)amide 5-[((4-(3-phenyl-n-propylamino)phenylsulfonyl)-amino)carbonyl]- pyridine-2-carboxylic acid.

Example 510

(2-oxyethyl)amide 5-[((4-(2-phenylacetylamino)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 511

(2-oxyethyl)amide 5-[((4-(benzoylamine)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 512

(2-oxyethyl)amide 5-[((4-(acetylamino)phenylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 513

(2-oxyethyl)amide 5-[((4-(n-propylamino)phenylsulfonyl)amino)carbonyl] - pyridine-2-carbonitriding-2-carboxylic acid.

Example 515

(2-oxyethyl)amide 5-[((4-((2-phenoxyacetyl)amino)phenylsulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 516

(2-oxyethyl)amide 5-[((4-(n-butanolate)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 517

(2-oxyethyl)amide 5-[((4-(cyclohexylamino)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 518

(2-oxyethyl)amide 5-[((4-(cyclohexylethyl)amino)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 519

(2-methoxyethyl)amide 5-[((4-(4-phenyl-n-butanolate)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 520

(2-methoxyethyl)amide 5-[((4-(3-phenyl-n-propionamido)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 521

(2-methoxyethyl)amide 5-[((4-(2-phenylacetylamino)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 522

(2-methoxyethyl)amide 5-[((4-(benzoylamine)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 523

(2-methoxyethyl)amide 5-[((4-acetylamino)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 524

(2-IU Example 525

(2-methoxyethyl)amide 5-[((4-n-hexanamine)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 526

(2-methoxyethyl)amide 5-[((4-(2-phenoxyacetyl)amino)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 527

(2-methoxyethyl)amide 5-[((4-(n-butanolate)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 528

(2-methoxyethyl)amide 5-[((4-(cyclohexylamino)phenylsulfonyl)amino) carbonyl]-pyridine-2-carboxylic acid.

Example 529

(2-methoxyethyl)amide 5-[((4-(cyclohexylethyl)amino)phenylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

Example 530

(Glycyl-2-propyl ester)amide 5-[(((4-phenyl-n-butyl) sulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 531

(Glycyl-2-propyl ester)amide 5-[(((2-phenoxyethyl) sulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 532

(Glycyl-2-propyl ester)amide 5-[((2-(4-pertenece) ethylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 533

(Pitilessly ester)amide 5-[((phenylsulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 534

(Picibanil/BR> (Pitilessly ester)amide 5-[(((2-(4-forfinal)ethyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 536

(Pitilessly ester)amide 5-[(((2-(4-methoxyphenyl)ethyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 537

(Pitilessly ester)amide 5-[(((3-phenyl-n-propyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 538

(Pitilessly ester)amide 5-[(((4-phenyl-n-butyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 539

(Pitilessly ester)amide 5-[(((2-phenoxyethyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 540

(Pitilessly ester)amide 5-[(((2-(4-pertenece)ethyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 541

Glycolipid 5-[((phenylmethylsulfonyl)amino)carbonyl] -pyridine-2 - carboxylic acid.

Example 542

Glycolipid 5-[(((2-phenylethyl)sulfonyl)amino)carbonyl] -pyridine - 2-carboxylic acid.

Example 543

Glycolipid 5-[(((2-(4-forfinal)ethylsulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 544

Glycolipid 5-[(((2-(4-methoxyphenyl)ethyl)sulfonyl)amino)carbonyl]- pyridinones acid.

Example 546

Glycolipid 5-[(((4-phenyl-n-butyl)sulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 547

Glycolipid 5-[(((2-phenoxyethyl)sulfonyl)amino)carbonyl] - pyridine-2-carboxylic acid.

Example 548

Glycolipid 5-[(((2-(4-pertenece)ethyl)sulfonyl)amino)carbonyl]- pyridine-2-carboxylic acid.

Example 549

(Glycyl-3-pentalogy ester)amide 5-[((phenylmethylsulfonyl)amino) carbonyl] -pyridine-2-carboxylic acid.

An example of 550

(Glycyl-3-pentalogy ester)amide 5-[(((2-phenylethyl)sulfonyl)amino) carbonyl]-pyridine - 2-carboxylic acid.

Example 551

(Glycyl-3-pentalogy ester)amide 5-[(((2-(4-forfinal)ethyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 552

(Glycyl-3-pentalogy ester)amide 5-[(((2-(4-methoxyphenyl)ethyl) sulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 553

(Glycyl-4-p ester)amide 5-[(((3-phenyl-n-propyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 554

(Glycyl-R-2-butyl ester)amide 5-[(((4-phenyl-n-butyl)sulfonyl) amino)carbonyl]-pyridine-2-carboxylic acid.

Example 555

(Glycyl-n-oktilovom ester)amide 5-[(((2-phenoxyacetyl)amide 5-[(((2-(4-pertenece)ethyl) sulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 557

(2-ethoxyethyl)amide 5-[((4-(2-((3,4-dimethoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 558

(2-acetoxyethyl)amide 5-[((4-(2-((3,4-dimethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 559

(2-oxyethyl)amide 5-[((4-(2-((2,5-dimethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 560

(2-methoxyethyl)amide 5-[((4-(2-((3,4-dimethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 561

(2-ethoxyethyl)amide 5-[((4-(2-((3,4-dimethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 562

(2-methoxyethyl)amide 5-[((4-(2-((2,5-dimethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 563

(Glycemically ester)amide 5-[((4-(2-((3,4-dimethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 564

(Glycylation ester)amide 5-[((4-(2-((3,4-dimethoxybenzoyl)amino) ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 565

(Glycol acid.

Example 566

(Glycyl-2-propyl ester)amide 5-[((4-(2-((3,4-dimethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 567

(Glycyl-3-pentalogy ester)amide 5-[((4-(2-((3,4-dimethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 568

(Glycyl-2-propyl ester)amide 5-[((4-(2-((2,5-dimethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 569

Glycolipid 5-[((4-(2-((3,4-dimethoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 570

(Glycylcyclines ester)amide 5-[((4-(2-((3,4-dimethoxybenzoyl) amino)ethyl)phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

Example 571

Glycolipid 5-[((4-(2-((2,5-dimethoxybenzoyl)amino)ethyl) phenylsulfonyl)amino)carbonyl]-pyridine-2-carboxylic acid.

1. Amides of sulfonamide and sulfonamidophenylhydrazine-2-carboxylic acids of the formula I

< / BR>
where A is R3and B-X - NR6R7or B = R3and A - -X - NR6R7;

X is a simple bond or-CO-;

R1, R2, R3- same or different, hydrogen, unsubstituted C1
1- C8-alkyl, C6- C10-aryl, C7-C11ar-C1-C6-alkyl, C1-C8-alkyloxy may once substituted by hydroxy, carboxy, C1-C6-allyloxycarbonyl, C1-C6-alkoxy;

R6is hydrogen, C1-C6-alkyl, - physiologically acceptable monovalent cations, in particular Na+, K+;

R7- the remainder of the formula II (except in - SO2H)

Y - [C-U]r-D-W,

Y - SO2;

C - bond or unbranched or branched aliphatic C1-C8-alcander; U is a bond, -O-; D is a bond; W is hydrogen, thienyl, C6-C10-aryl, and U represents-O -, if C does not mean a relationship, and W is preferably substituted, for example, by the group:

-O-(CH2]xCfH(2f+1-q)Fq;

f = 1-8, preferably 1-5;

q = 0.1 to (2f + 1);

r = 1, 2;

x = 0-8.

2. The compound of formula I under item 1, where W is substituted by 1 to 2 groups, including: halogen, trifluoromethyl, C1- C8-alkyl, C6-C10-aryl, C1-C8-alkoxy, C1-C8-alkoxy - C1-C8-alkyl, C6- C10-aryloxy, N-(C1- C8-allylcarbamate,

N,N-di-C10)-aryl-(C1-C8)-alkyl]carbarnoyl, N-(C1-C8)-alkyl-C6-C10-arylcarbamoyl, N-C1-C8-alkoxycarbonyl, C1-C8-alkanoyl-N-C1-C8-alkylamino, C6-C10-aryloxy-C1-C8-alkanoyl-N-C1-C8-alkylamino,

C1-C8-alkanolamine, cyclo-C3-C8-alkanolamine, C6-C10ar-C1-C8-alkanolamine, N-C1-C8-allylcarbamate-C1-C8-alkyloxy-C6-C10-aryl, C3-C8-cycloalkyl-C1-C6-alkanolamine-C1-C8-alkyl, C6-C10aryloxy-C1-C8-alkanolamine, C6-C10-aroyl-N-(C1-C8)-alkylamino, C7-C11ar-C1-C6-alkanoyl-N-(C1-C10)-alkylamino, C1-C8-alkanolamine-C1-C8-alkyl, C3-C8-cycloalkanones-C1-C8-alkyl, C6-C10-aroylamino-C1-C8-alkyl,

C7-C11ar-C1-C8-alkanolamine-C1-C8-alkyl;

3. The compound of formula I under item 1 or 2, where R1, R2and R3the same or different and mean a hydrogen atom, a C1-C3-alkyl, C1-C31-C8-alkoxy, C1-C8-alkyl, C6-C10-aryl, preferably unsubstituted or substituted phenyl, benzyl or phenethyl, C7-C11ar-C1-C6-alkyl, possibly substituted once hydroxy, carboxy, C1-C6-allyloxycarbonyl, C1-C6-alkoxy, R6means a hydrogen atom, a physiologically acceptable monovalent cations, in particular Na+, K+, R7means the residue of formula II, in which C denotes a (C1-C6)-alcander and r = 1.

4. The compound of formula I according to any one of paragraphs.1 to 3, where R1, R2and R3means a hydrogen atom, R4means a hydrogen atom, R5means phenyl, benzyl or phenethyl, non-branched C1-C4-alkyl, substituted C1-C4-alkoxygroup, carboxyla, R7denotes a residue of formula II, in which C represents C1-C4-alcander and r = 1.

5. Pharmaceutical composition having antifibrotic activity, including the active agent and a carrier, wherein the active means it has a connection on p. 1 in an effective amount.

6. The method of obtaining compounds of General formula I on p. 1, where X o is arboxylic formula II

< / BR>
where A' - R3and B' - -other6or A' -other6and B' - R3,

subjected to interaction with the sulfonic acid derivative of General formula 3

Z - R7,

where Z is tsepliaeva group,

and the resulting compound II, where A1- R3B1- -NR6R7or A1- NR6R7and B1- R3, is subjected to the interaction with the amine of formula 5

H-NR4R5< / BR>
with the formation of compounds of General formula I, where A, B, R1, R2, R4, R5, R6, R7listed in paragraph 1.

7. The method of obtaining compounds of General formula I on p. 1, where X IS-CO-, and R1- R7have the values specified in paragraph 1, wherein the carboxylate ester pyridine-2-carboxylic acid of formula 7

< / BR>
where A" - R3B" - CO2H or A - CO2H and B" - R3,

subjected to interaction with the sulfonic acid derivative of formula 8

R6HNR7< / BR>
and the resulting compound of formula 7, where A" - R3B" - -CONR6R7or A" - -CONR6R7and B" - R3subjected to interaction with the amine of formula 5

HNR4R5,

where R1, R2, R3, R4, R5, R6, R7 is UNCTAD:

24.03.92 on PP.1, 5, 6, 7 except W-thienyl, r is 2, p. 2 the following radicals: halogen, trifluoromethyl, C1-C8-alkoxy, N-C3-C8-allylcarbamate, N, N-di-C1-C8-allylcarbamate, N-(C3-C8-cycloalkylcarbonyl, C1-C8-alkanolamine, cyclo-C3-C8-alkanolamine, C6-C10ar-C1-C8-alkanolamine, C6-C10-aroyl-N-(C1-C8)-alkylamino, C7-C11-ar-(C1-C6-alkanoyl-N-C1-C10-alkylamino;

14.11.92 on PP. 1, 5, 6, 7, where W is thienyl, r is 2, p. 2 the following radicals: C6-C10-aryl, C1-C8-alkoxy-C1-C8-alkyl, C6-C10-aryloxy, N-(C1-C8)-alkyl-N-[(C6-C10-aryl-(C1-C8)-alkyl] -carbarnoyl, N-(C1-C8)-alkyl-C6-C10-arylcarbamoyl, N-(C1-C8-alkoxycarbonyl, C6-C10-aryloxy-C1-C8-alkanoyl-N-(C1-C8)-alkylamino, N-(C1-C8-allylcarbamate-C1-C8-alkyloxy-C6-C10-aryl, C3-C8-cycloalkyl-C1-C6-alkanolamine-C1-C8-alkyl, C6-C10-aryloxy-C1-C8-alkanolamine, C1-C8alkanoyl the 0-aroylamino-C1-C8-alkyl,

C7-C11ar-C1-C8-alkanolamine-C1-C8-alkyl.

 

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< / BR>
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10 cl, 3 tbl

FIELD: medicine, toxicology.

SUBSTANCE: invention proposes applying 15% aqueous solution of 1-methyl-5-[2'-(benzyldimethylammonio)ethyl]carbamoyl pyridinium-2-aldoxime dichloride that exceeds the 15% solution of dipiroxime (TMB-4, trimedoxime bromide) used in native medicinal practice by the curative effectiveness. Invention can be used in urgent treatment of acute poisoning with organophosphorus poisonous substances eliciting neuroparalytic effect.

EFFECT: enhanced effectiveness, valuable medicinal properties of agent.

3 tbl

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new sulfur-containing compounds of the formula (I):

their pharmaceutically acceptable salts or solvates, or salt solvates wherein R1 represents (C1-C6)-alkyl, cycloalkyl, aryl, aliphatic or aromatic heterocyclyl substituted with one more basic group, such as amino-, amidino- and/or guanidine-group; R2 represents hydrogen atom (H), alkyl, alkylthio-, alkoxy- or cycloalkyl group; R3 represents COOR5, SO(OR5), SOR5 and others; R4 represents hydrogen atom (H) or (C1-C6)-alkyl; R6 represents hydrogen atom (H); X represents C(Z)2 or NR6CO; Y represents C(Z)2; Z represents hydrogen atom (H), (C1-C6)-alkyl, aryl or cycloalkyl. Indicated compounds inhibit activity of carboxypeptidase U and can be used for prophylaxis and treatment of diseases associated with carboxypeptidase U.

EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.

14 cl, 36 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new sulfur-containing compounds of the formula (I):

their pharmaceutically acceptable salts or solvates, or salt solvates wherein R1 represents (C1-C6)-alkyl, cycloalkyl, aryl, aliphatic or aromatic heterocyclyl substituted with one more basic group, such as amino-, amidino- and/or guanidine-group; R2 represents hydrogen atom (H), alkyl, alkylthio-, alkoxy- or cycloalkyl group; R3 represents COOR5, SO(OR5), SOR5 and others; R4 represents hydrogen atom (H) or (C1-C6)-alkyl; R6 represents hydrogen atom (H); X represents C(Z)2 or NR6CO; Y represents C(Z)2; Z represents hydrogen atom (H), (C1-C6)-alkyl, aryl or cycloalkyl. Indicated compounds inhibit activity of carboxypeptidase U and can be used for prophylaxis and treatment of diseases associated with carboxypeptidase U.

EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.

14 cl, 36 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes N-substituted azaheterocyclic carboxylic acids and their esters of the formula (I):

wherein R1 and R2 represent independently hydrogen, halogen atom, NR6R7 or (C1-C6)-alkyl; Y represents >N-CH2 or >C=CH2- wherein only underlined atom is a component of the ring system; X represents -O-, -S-, -CH2CH2- wherein R6 and R7 represent independently (C1-C6)-alkyl; r = 1, 2 or 3; Z represents heterocycle taken among formulas (a), (b), (c), (d), (f), (k), (g) and (j) given in the invention claim. Also, invention relates to a method for their preparing and pharmaceutical composition based on compounds of the formula (I). Invention describes a method for inhibition of neurogenous pain, inflammation and blood glucose level increase to patient by administration to patient the effective dose of compound of the formula (I). Compounds of the formula (I) elicit ability to inhibit the neurogenous pain and blood glucose enhanced level.

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

13 cl, 1 tbl, 30 ex

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