Dpp-iv inhibitors

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to novel compounds of general formula (I) Z-C(R1R2)-C(R3NH2)-C(R4R5)-X-N(R6R7) (I), or its pharmaceutically acceptable salt which is different because Z represents phenyl; where Z can be substituted with one or more R8, where R8 represents halogen; R1, R4 represent H; R2, R5 represent H; R3 represents H; X is selected from group consisting of S(O)2 and C(O); R6, R7 are independently selected from group consisting of H, (C(R29R30))m-X1-Z1 and (C(R31R32))n-X2-X3-Z2 and C1-4alkyl, which carries substitution with one or more R29a, where R29a is independently selected from group consisting of R29b and Z1, on condition that R6 and R7 are selected in such way that R6 and R7 were not simultaneously independently selected from group consisting of H, CH3, CH2CH3, CH2CH2CH3 and CH(CH3)2; R29 R29b, R30, R31, R32 are independently selected from group consisting of H, C1-6alkyl and N(R32a)-C1-6alkyl; R32a represents C1-6alkyl; m is 0, 1 or 2; n is 2; X1 is independently selected from group consisting of covalent bond, -C1-6alkyl and -C1-6alkyl-N(R33)-; X2 represents -N(R35)-; X3 represents -C(O)-; R33 represents C1-6alkyl; R35 represents H; Z1, Z2 are independently selected from group consisting of Z3 and -C(R37a)Z3aZ3b; R37a represents H; Z3, Z3a, Z3b are independently selected from group consisting of T1, T2, C1-6alkyl, C1-6alkyl-T1 and C1-6alkyl-T2; T1 represents phenyl; where T1 is optionally substituted with one or more R38; R38 being independently selected from group consisting of halogen, CN, R39, C(O)NH2, S(O)2NH2, OT3, C(O)N(R40)T3 and T3, T2 is selected from group consisting of C3-7cycloalkyl, indanyl, tetralinyl, heterocycle and heterobicycle, T2 optionally carries substitution with one or more R41, where R41 is independently selected from group consisting of halogen, R42, OH and T3; R39 is selected from group consisting of C1-6alkyl, O-C1-6alkyl, S-C1-6alkyl, C(O)N(R44)-C1-6alkyl, S(O)-C1-6alkyl and S(O)2-C1-6alkyl, where each C1-6alkyl optionally carries substitution with one or more R45, where R45 is independently selected from group consisting of F, N(R46R47) and T3; R42 represents C1-6alkyl, each C1-6alkyl optionally carries substitution with one or more R45, where R45 is independently selected from group consisting of F; R40, R46, R47 are independently selected from group consisting of H and C1-6alkyl; R44 represents H; T3 is selected from group consisting of T4 and T5; T4 represents phenyl, where T4 optionally carries substitution with one or more R51, where R51 is independently selected from group consisting of halogen, OR52, S(O)2N(R52R53), C1-6alkyl; R52, R53 are independently selected from group consisting of H and C1-6alkyl; T5 is selected from group consisting of heretocycle C3-7cycloalkyl, where T5 optionally carries substitution with one or more R54, where R54 represents C1-6alkyl; where heterocycle represents ring of cyclobutane, cyclopentane, cyclohexane, which can contain double bonds in number up to maximal, or aromatic or non-aromatic ring which is fully or partially saturated or unsaturated, and in which at least one carbon atom, maximally up to four carbon atoms, are substituted with heteroatom, selected from group including oxygen and nitrogen, and where ring is bound with remaining part of molecule through carbon or nitrogen atom; where heterobicycle represents heterocycle as stated above, which is condensed with phenyl or other heterocycle with formation of bicyclic ring system, on condition that the following compound is excluded from claim:3-amino-N-cyclohexyl-4-phenylbutyramide. Invention also relates to pharmaceutical composition based on compound of general formula (I) and to their application for manufacturing medication for treatment and/or prevention of conditions during which it is desirable to inhibit DPP-IV.

EFFECT: obtaining novel group of compounds possessing useful biological properties.

26 cl, 8 tbl, 193 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

or its pharmaceutically acceptable salt, characterized in that

Z represents phenyl; where Z may be substituted by one or more

R8where R8is a halogen;

R1, R4represent N;

R2, R5represent N;

R3represents N;

X is selected from the group consisting of S(O)2and C(O);

R 6, R7independently selected from the group consisting of H, (C(R29R30))mX1-Z1and (C(R31R32))n-X2-X3-Z2and C1-4alkyl, which is substitution by one or more R29awhere R29aindependently selected from the group consisting of R29band Z1provided that R6and R7chosen so that R6and R7were not at the same time independently selected from the group consisting of N, CH3CH2CH3CH2CH2CH3and CH(CH3)2;

R29R29b, R30, R31, R32independently selected from the group consisting of H, C1-6the alkyl and N(R32a)-C1-6of alkyl;

R32arepresents a C1-6alkyl;

m is 0, 1 or 2;

n = 2;

X1independently selected from the group consisting of a covalent bond, -C1-6the alkyl and-C1-6alkyl-N(R33)-;

X represents-N(R35)-;

X3represents-C(O)-;

R33represents a C1-6alkyl;

R35represents N;

Z1, Z2independently selected from the group consisting of Z3and-C(R37aZ3aZ3b;

R37arepresents N;

Z3, Z3a, Z3bindependently selected from the gr is PPI, consisting of T1T2C1-6of alkyl, C1-6alkyl-T1and C1-6alkyl-T2;

T1represents phenyl; where T1optional substitution is with one or more R38; and R38independently selected from the group consisting of halogen, CN, R39C(O)NH2, S(O)2NH2FROM3C(O)N(R40T3and T3T2selected from the group consisting of C3-7cycloalkyl, indanyl, tetralinyl, heterocycle and heterobicycle, and T2optional substitution is with one or more R41where R41independently selected from the group consisting of halogen, R42, OH and T3;

R39selected from the group consisting of C1-6of alkyl, O-C1-6of alkyl, S-C1-6of alkyl, C(O)N(R44)-C1-6of alkyl, S(O)-C1-6the alkyl and S(O)2-C1-6of alkyl, where each C1-6alkyl optional substitution is with one or more R45where R45independently selected from the group consisting of F, N(R46R47and T3;

R42represents a C1-6alkyl, each C1-6alkyl optional substitution is with one or more R45where R45independently selected from the group consisting of F;

R40, R46, R47independently selected from the group consisting of N and C1-6of alkyl;

R 44represents N;

T3selected from the group consisting of T4and T5;

T4represents phenyl, where T4optional substitution is with one or more R51where R51independently selected from the group consisting of halogen, OR52, S(O)2N(R52R53)1-6of alkyl;

R52, R53independently selected from the group consisting of N and C1-6of alkyl;

T5selected from the group consisting of heterocycle With3-7cycloalkyl, where T5optional substitution is with one or more R54where R54represents a C1-6alkyl;

where the heterocycle represents a ring CYCLOBUTANE, cyclopentane, cyclohexane, which may contain double bonds in the amount up to the maximum, or an aromatic or nonaromatic ring which is partially or fully saturated or unsaturated, and in which at least one carbon atom and up to a maximum of four carbon atoms are replaced by a heteroatom selected from the group comprising oxygen and nitrogen, and where the ring is connected with the rest of the molecule through a carbon atom or nitrogen;

where heterobicycle refers to a heterocycle, as defined above, which is condensed with a phenyl or another heterocycle with the formation of bicyclic with the system of rings,

provided that the following compound is excluded from the claims:

3-amino-N-cyclohexyl-4-phenylbutyramide.

2. The compound according to claim 1 of formula (Ia)

or its pharmaceutically acceptable salt, wherein Z, R1-R7and X have the meanings indicated in claim 1.

3. The compound according to claim 1, wherein Z may be substitution of 1 or 2, R8that may be the same or different.

4. The compound according to claim 1, wherein Z represents 2-forfinal.

5. The compound according to claim 1, wherein R6selected from the group consisting of N and CH3.

6. The compound according to claim 1, wherein X1is a covalent bond.

7. The compound according to claim 1, wherein R7represents the Z1.

8. The compound according to claim 1, wherein R7represents a C1-4alkyl, substituted by 1-4 R29athat may be the same or different.

9. The compound according to claim 1, wherein R29aselected from the group consisting of R29band Z1and where R29brepresents N(CH3)2.

10. The compound according to claim 1, wherein R29aselected from the group consisting of R29band Z1where Z1selected from the group consisting of T1and T2.

11. Connected is E. according to claim 1, characterized in that the T1represents phenyl, and where T1optional substitution is one or three, R38that may be the same or different.

12. The compound according to claim 1, wherein R38independently selected from the group consisting of F, Cl, CN, CH3With2H5CH2CH2CH3CH(CH3)2, CF3, O-CH3And O2H5. S-CH3, SO2NH2T3and O-T3.

13. The compound according to claim 1, characterized in that the T2selected from the group consisting of

and where T2may be substitution of one or two R41that may be the same or different.

14. The compound according to claim 1, wherein R41selected from the group consisting of HE, CH3and T3;

15. The compound according to claim 1, characterized in that the T represents the T4.

16. The compound according to claim 1, characterized in that the T4represents phenyl, where T4may be substitution of one to three R51that may be the same or different.

17. The compound according to claim 1, wherein R51independently selected from the group consisting of F, Cl, O-CH3And O2H5.

18. The compound according to claim 1, characterized in that the T3represents the T5.

19. The compound according to claim 1, characterized in that the T5represents a heterocycle, where T5may be substitution of one or two R54that may be the same or different.

20. The compound according to claim 1, wherein R54represents CH3.

21. The compound according to claim 1, selected from the group consisting of

22. Pharmaceutical composition for treatment and/or prevention of conditions in which it is desirable inhibition of DPP-IV containing the compound according to any one of claims 1 to 21 or its pharmaceutically acceptable salt together with a pharmaceutically acceptable carrier.

23. The pharmaceutical composition according to claim 2, containing one or more additional compounds or their pharmaceutically acceptable salts selected from the group consisting of other compounds according to any one of claims 1 to 21; another inhibitor of DPP-IV; insulin sensitizers; agonists RAPP; biguanides; inhibitors of protein tyrosinosis-1B (PTP-1B); insulin and insulin mimetics; sulfonylureas and other substances that stimulate insulin secretion, inhibitors α-glucosidase, antagonists of receptors for glucagon, like peptide (GLP-1)mimetics GLP-1 and agonists of receptors for GLP-1, gastrointestinal peptide (GIP), mimetics of the ISU and agonists of the receptors to the ISU; peptide that activates the pituitary adenylate cyclase (RASAR), mimetics of RASER and agonists of the receptor 3 to RASAR; drugs that reduce cholesterol, inhibitors of HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A-reductase); sequestrants; nicotineamide alcohol, nicotinic acid and its salts, agonists RAPPα (PPARα); agonists of PPAR-α/γ dual-action inhibitors cholesterol intake, inhibitors of acyl-COA-cholesterol acyltransferase, antioxidants, agonists RAPPδ, compounds for the treatment of obesity, an inhibitor of the ideal vector of bile acids and anti-inflammatory drugs.

24. The compound or its pharmaceutically acceptable salt is about any one of claims 1 to 21 for use as a drug for the treatment and/or prevention of conditions when it is desirable inhibition of DPP-IV.

25. The use of compound or its pharmaceutically acceptable salt according to any one of claims 1 to 21 for the manufacture of a medicine for the treatment and prevention of non-insulin dependent diabetes mellitus (Type II), hyperglycemia, obesity, resistance to insulin, disorders of lipid metabolism, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL, high LDL levels, atherosclerosis, growth hormone deficiency, diseases associated with immune responses, HIV infection, neutropenia, neuronal diseases, metastasis of tumors, benign prostate hypertrophy, gingivitis, hypertension, osteoporosis, diseases associated with sperm motility, low glucose tolerance, resistance to insulin, its consequences, restenosis of blood vessels, irritable bowel syndrome, inflammatory bowel disease, including Crohn's disease and ulcerative colitis, other inflammatory conditions, pancreatitis, abdominal obesity, neurodegenerative diseases, anxiety, depression, retinopathy, nephropathy, neuropathy, syndrome X, ovarian hyperandrogenism (polycystic ovarian syndrome), diabetes Type II or growth hormone deficiency.

26. The use of compounds according to any one of claims 1 to 21 as in the of ibitira DPP-IV.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel soluble pharmaceutical salts formed from salt-forming active compound of the general formula (I) or (II) and sugar substitute that can be used in preparing medicinal agents useful in pain and enuresis treatment. Salt-forming active substance represents a salt-forming compound among 1-phenyl-3-dimethylaminopropane compounds of the general formula (I) wherein X means -OH, F, Cl, H or group -OCOR6; R1 represents (C1-C4)-alkyl group; R2 represents H or (C1-C4)-alkyl group; R3 represents H or (C1-C4)-alkyl group with a direct chain, or R2 and R3 form in common (C4-C7)-cycloalkyl group and if R5 means H then R4 represents group O-Z in meta-position wherein Z means H,(C1-C3)-alkyl, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl), -CONH-C6H4-(C1-C3-alkyl), -CO-C6H4-R7 wherein R7 represents -OCO-C1-C3-alkyl in ortho-position or group -CH2N(R8)2 in meta- or para-position and wherein R8 means (C1-C4)-alkyl or 4-morpholino-group, either R4 represents S-(C1-C3)-alkyl in meta-position, meta-Cl, meta-F, group -CR9R10R11 in meta-position wherein R9, R10 and R11 mean H or F, group -OH in ortho-position, O-(C2-C3)-alkyl in ortho-position, para-F or group -CR9R10R11 in para-position wherein R9, R10 and R11 mean H or F, or if R5 means Cl, F, group -OH or O-C1-C3-alkyl in para-position then R4 means Cl, F, group -OH or O-(C1-C3)-alkyl in meta-position, or R4 and R5 form in common group 3,4-OCH=CH- or OCH=CHO-; R6 means (C1-C3)-alkyl, or salt-forming active substance represents a salt-forming compound among 6-dimethylaminomethyl-1-phenylcyclohexane compounds of the general formula (II) wherein R1' represents H, -OH, Cl or F; R2' and R3' have similar or different values and represent H, (C1-C4)-alkyl, benzyl, -CF3, -OH, -OCH2-C6H5, O-(C1-C4)-alkyl, Cl or F under condition that at least one among radicals R2' either R3' means H; R4' represents H, -CH3, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl, -CO-NH-C6H4-(C1-C3)-alkyl, -CO-C6H4-R5', CO-(C1-C5)-alkyl), -CO-CHR6'-NHR7' or unsubstituted either substituted pyridyl, thienyl, thiazolyl or phenyl group; R5' represents -OC(O)-(C1-C3)-alkyl in ortho-position or -CH2N(R8')2 in meta- or para-position and wherein R8' means (C1-C4)-alkyl, or both radicals R8' in common with nitrogen atom (N) form 4-morpholino-group, and R6' and R7' have similar or different values and represent H or (C1-C6)-alkyl under condition that if both radicals R2' and R3' represent H then R4' doesn't mean -CH3 when R1' represents additionally H, -OH or Cl, either R4' doesn't mean H when R1' represents additionally -OH. Also, invention relates to a medicinal agent based on indicated salts.

EFFECT: valuable medicinal properties of salts and drug.

14 cl, 1 tbl, 8 ex

The invention relates to compounds of General formula I

including their optical isomers and mixtures of such isomers, where r1denotes hydrogen, C1-C6alkyl, C3-C6cycloalkyl or aryl, optionally substituted by 1-3 halogen atoms, R2and R3each independently of one another denote hydrogen or C1-C6alkyl, R4stands WITH1-C6alkyl or C3-C6quinil, R5, R6, R7and r8each denotes hydrogen and

,

r10denotes aryl, optionally substituted by 1-3 substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl,1-WITH4haloalkoxy,1-C4alkoxy, C1-C4alkyl, C1-C6alkylthio,3-C6alkyloxy, nitro and C1-C6alkoxycarbonyl or optionally substituted heteroaryl representing aromatic kolicevo the t hydrogen, WITH1-C6alkyl or C3-C6quinil, R12denotes hydrogen or C1-C6alkyl, Z represents hydrogen,- CO-R16or-CO-COOR16and R16stands WITH1-C6alkyl, -CH2-CO - C1-C6alkyl or phenyl

The invention relates to bicyclic compounds useful as drugs, the neutralizing effect of glycoprotein IIb/IIIa, to prevent thrombosis

Herbicide // 2070798
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Casr antagonist // 2315036

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel compound represented by the following formula (1) , its pharmaceutically acceptable salts or optically active isomers wherein each symbol is given in the invention description. Proposed compound possesses antagonistic effect with respect to calcium-sensitive receptor (CASR). Also, invention relates to a therapeutically medicinal agent used in treatment of osteoporosis based on this compound, to a method for treatment of osteoporosis, calcium receptor antagonist and to agent promoting secretion of parathyroid hormone (PTH).

EFFECT: valuable medicinal properties of antagonist.

33 cl, 66 tbl, 5 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention reports about preparing new substituted derivatives of 2-dialkylaminoalkylbiphenyl of the general formula (I):

wherein n = 1 or 2; R1 means cyano-group (CN), nitro-group (NO2), SO2CH3, SO2CF3, NR6aR7a, acetyl or acetamidyl; R2 means hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), cyano-group (CN), nitro-group (NO2), CHO, SO2CH3, SO2CF3, OR6, NR6R7, (C1-C6)-alkyl, acetyl or acetamidyl being alkyl can comprise one or more similar or different substitutes taken among halogen atom or hydroxy-group; or R1 and R mean in common group -OCH2O, -OCH2CH2O, CH=CHO, CH=C(CH3)O or CH=CHNH; R3 means H, F, Cl, Br, CN, NO2, CHO, SO2CH3, SO2CF3, OR6, NR6R7, (C1-C6)-alkyl, acetyl or acetamidyl being alkyl can comprise one or more similar or different substitutes taken among halogen atom or hydroxy-group; R4 and R5 have similar or different values and mean hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R6 and R7 have similar or different values and mean hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R6a means hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R7a means unsubstituted (C1-C6)-alkyl as their bases and/or salts of physiologically acceptable acids, with exception of compound representing 4-chloro-2'-dimethylaminomethylbiphenyl-2-carbonitrile and to a method for their preparing. Derivatives of 2-dialkylaminoalkylbiphenyl can be used in medicine for treatment or prophylaxis of pains, inflammatory and allergic responses, depressions, narcomania, alcoholism, gastritis, diarrhea, enuresis, cardiovascular diseases, respiratory ways diseases, cough, psychiatry disorders and/or epilepsy.

EFFECT: valuable medicinal properties of compounds.

13 cl, 2 tbl, 43 ex

The invention relates to new nitromethylene formula (I)

< / BR>
in which A represents C6-C10aryl, thienyl, benzothiazyl; X denotes halogen, cyano, C1-C7alkyl, trifluoromethyl, C2-C7alkoxy, or cryptometer; p is chosen from 0, 1, 2, 3, 4, or 5; Z represents a bond, -CO-NH-, SO2-NH-, a sulfur atom, sulfinyl group or a C2-C7alkenylamine radical; R1, R2, R3and E indicated in paragraph 1

The invention relates to new N-substituted piperidinylmethyl f-ly I, their N-oxide forms, isomers, and salts, where R1- halogen, C1-6alkylsulfonamides And divalent radical-CH2-CH2; -CH2-CH2-CH2- or-CH=CH-; R2is hydrogen or C1-6alkyloxy; L is a radical of formula-Alk-R4, -Alk-OR5, -Alk-NR6R7; Alk-C1-12alcander; R4is hydrogen, cyano, C1-6alkylsulphonyl,1-6allyloxycarbonyl, etc

The invention relates to new compounds used in the pharmaceutical industry for the manufacture of medicines

The invention relates to new benzofuranol derivatives, process for their preparation and to contain these compounds in pharmaceutical compositions

FIELD: chemistry.

SUBSTANCE: in arylpiperazinyl compounds of general formula , where R1 is unsubstituted alkyl or cycloalkyl; R2 and R3 independently hydrogen; lower alkyl; cycloalkyl; or -NR4R5, where R4 and R5 independently represent H, O, R6 or COR6, where R6 can represent lower alkyl or sulfonamidoalkyl; on condition that R2 and R3 both are not hydrogen; -atoms designated as bound with dotted line, taken together with atoms, to which they are joined, can form six-member ring; - Z represents N or C; - m equals 0, 1 or 2; - n equals 1, 2, 3, 4, 5 or 6; - p equals 0, 1, 2, 3 or 4. Compounds can be used for treatment of diseases, mediated directly or indirectly by 5-HT receptors. Such diseases are disorders of central nervous system.

EFFECT: increase of composition and method of treatment efficiency.

50 cl, 12 dwg, 2 tbl, 41 ex

FIELD: organic chemistry, biochemistry, enzymes.

SUBSTANCE: invention relates to compounds represented by the formula: wherein values of substitutes are given in the invention description. Also, invention relates to pharmaceutically acceptable salts of the compound that can be used in treatment and/or prophylaxis of cathepsin-dependent states or diseases of mammals. Proposed compound are useful in treatment of diseases wherein bone resorption inhibition is desired, such as osteoporosis, increased mineral density of bone and reducing risk of fractures. Proposed claimed compounds are designated for preparing a drug possessing the inhibitory activity with respect to cathepsin.

EFFECT: valuable medicinal and biochemical properties of compounds.

24 cl, 13 sch, 4 tbl, 15 ex

.FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their physiologically acceptable salts also possessing properties for decrease the blood sugar content. In compound of the formula (I) A means phenyl wherein phenyl residue can be substituted up to three times with fluorine (F), chlorine (Cl) and bromine (Br) atoms; R1 and R2 mean hydrogen atom (H); R3, R4, R5 and R6 mean independently of one another H, F, Cl, Br, -NO2, -O-(C1-C6)-alkyl, (C1-C6)-alkyl, -COOH; R7 means H, (C1-C6)-alkyl wherein alkyl can be substituted up to three times with -OH, -CF3, -CN, COOH, -COO-(C1-C6)-alkyl, -CO-NH2, -NH2, -NH-(C1-C6)-alkyl, -N-[(C1-C6)-alkyl]2, -NHCO-(C1-C6)-alkyl, -NHCOO-(C1-C6)-alkyl or -NHCOO-(C1-C4)-alkylenephenyl; in (CH2)m m can mean 0-6 and aryl means phenyl, O-phenyl, CO-phenyl, benzo[1,3]dioxolyl, pyridyl, indolyl, piperidinyl, tetrahydronapthyl, 2,3-dihydrobenzo[1,4]dioxynyl, benzo[1,2,5]thiadiazolyl, pyrrolidinyl, morpholinyl wherein aryl residue can be substituted mono- or multiple with R9 wherein R9 means F, Cl, Br, -OH, -NO2, -CF3, -OCF3, (C1-C6)-alkyl, (C1-C6)-alkyl-OH, -O-(C1-C6)-alkyl, -COOH, -COO-(C1-C6)-alkyl. Also, invention relates to a pharmaceutical composition and a method for preparing a medicinal agent.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

7 cl, 2 sch, 1 tbl, 293 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I) as separate stereoisomers and their mixtures, or their physiologically acceptable salts possessing with inhibitory effect on VIIa factor. In the general formula of compounds of the formula (I) m = 0, 1, 2, 3 or 4; n = 0, 1, 2 or 3; A represents halogen atom; X represents oxygen atom; R1 is chosen from hydrogen atom, (C1-C6)-alkoxycarbonyl and (C6-C14)-aryloxycarbonyl wherein all aryl groups are free or substituted with (C1-C6)-alkoxy-group; R2is chosen from hydrogen atom, (C1-C6)-alkyl, (C6-C14)-aryl, (C6-C14)-aryl-(C1-C4)-alkyl, R20 -(C1-C6)-alkyl, R20-(C6-C14)-aryl and R20-(C6-C14)-(C1-C4)-alkyl wherein R20 is chosen from hydroxycarbonyl, aminocarbonyl; R3 is chosen from hydrogen atom, cyano-, hydroxy-group and (C1-C6)-alkyl; R4 is chosen from (C1-C6)-alkyl, (C-C14)-aryl, (C6-C14)-aryl-(C1-C4)-alkyl, Het and Het-(C1-C4)-alkyl wherin alkyl, atryl and Het groups are free or substituted with one or some similar or different substitutes R10; R5 is chosen from hydrogen atom, (C1-C6)-alkyl, (C6-C14)-aryl, (C6-C14)-aryl-(C1-C4)-alkyl wherein alkyl and aryl groups are free or substituted with one or some similar or different substituted R10; or R4 and R5 in common with carbon atom with that they are bound form saturated or unsaturated 5-6-membered ring that represents carbocyclic ring or heterocyclic ring comprising 1 or 2 similar ring heteroatoms chosen from nitrogen and oxygen atoms and possibly condensed with one or two saturated or unsaturated carbocyclic ring system comprising from 5 to 10 ring atoms wherein the final R4(R5)C-group is free or substituted with one or some similar or different substitutes R10; R6 is chosen from hydrogen atom and hydroxy-group. Also, invention relates to a method for synthesis of compound of the formula (I) and pharmaceutical composition based on thereof. Compounds of the formula (I) can be used in preparing medicinal agents useful for inhibition or decreasing blood coagulation or inflammatory response or for using in treatment of cardiovascular disorders, thrombo-embolic diseases or restenosis.

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

14 cl, 1 sch, 71 ex

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