Sphyngosine kinase inhibitors


FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula I or their pharmaceutically acceptable salts showing an ability to inhibit sphingosine kinase, to a based pharmaceutical composition, to a method of inhibiting sphingosine kinase and a method of treating diseases specified in breast cancer, diabetic retinopathy, arthritis and colitis. , wherein X represents -C(R3,R4)N(R5)-, -C(O)N(R4)-; R1 represents phenyl unsubstituted or substituted by 1 or 2 halogens. The values of R2, R3, R4, R5 substitutes are such as specified in the patent claim.

EFFECT: preparation of new compounds.

17 cl, 24 dwg, 9 tbl, 26 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

or its pharmaceutically acceptable salt, where
X represents-C(R3,R4)N(R5)-, -C(O)N(R4)-;
R1represents phenyl, unsubstituted or substituted by 1 or 2 Halogens;
R2is a (C3-C6)cycloalkyl, phenyl, (C1-C6)alkylphenyl, (C2-C6)alkenylphenol, (C2-C6)alkenylacyl, heteroaryl selected from benzoxazolyl, benzothiazolyl, indolyl, tetrazolyl, carbazolyl and purine, (C1-C6)alkylglycerol where heteroaryl selected from benzodioxolyl, pyridyl, imidazolyl, carbazolyl and tanila, 6-membered heteroseksualci containing 1 or 2 nitrogen atom as heteroatoms, (C1-C6)alkylchlorosilanes where heteroseksualci represents a 5-membered heteroseksualci containing 1 nitrogen atom, in the quality of the ve heteroatoms, which is optionally substituted by exography, or 6-membered heteroseksualci containing 2 heteroatoms selected from nitrogen and oxygen, mono(C1-C6)alkylamino(C1-C6)alkyl, -(C1-C6)alkyl-S-(C1-C6)alkyl, -diazolidinyl-thienylene, (C2-C6)alkenylphenol where heteroaryl selected from pyridyl, imidazolyl and carbazolyl, or (C2-C6)alkenylamine;
R3represents H or (C1-C6)alkyl;
where the alkyl and ring portion of each of the above R2groups is optionally substituted by up to 5 groups that are independently represent a (C1-C6)alkyl, halogen, halogen(C1-C6)alkyl, -OC(O)(C1-C6alkyl), -C(O)O(C1-C6alkyl), -CF3, -OCF3HE, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, -CN, -S-(C1-C6)alkyl, -SO2R' or R NR'r", where each alkyl part substituent is optionally optionally substituted by 1, 2 or 3 groups independently selected from CN, HE, NH2;
R4and R5independently represent H or (C1-C6)alkyl,
where R' and R" independently represent H or (C1-C6)alkyl,

2. The compound according to claim 1, where R2is a (C2-C6)alkenyl the Nile, (C2-C6)alkenylacyl, (C2-C6)alkenylphenol where heteroaryl selected from pyridyl, imidazolyl and carbazolyl, or -(C2-C6)alkenylphenol.

3. The compound according to claim 1, where R2is a (C2-C6)alkenylphenol or (C2-C6)alkenylacyl.

4. The compound according to claim 3, where the aryl portion (C2-C6)alkenylphenol or (C2-C6)alkenylacyl optionally substituted by 1 or 2 halogen, cyano or hydroxy.

5. The compound according to claim 1, where R2is a (C3-C6)cycloalkyl, phenyl, (C1-C6)alkylphenyl, heteroaryl selected from benzoxazolyl, benzothiazolyl, indolyl, tetrazolyl, carbazolyl and purine, (C1-C6)alkylglycerol where heteroaryl selected from benzodioxolyl, pyridyl, imidazolyl, carbazolyl and tanila.

6. The compound according to claim 1, where R2represents phenyl or (C1-C6)alkylphenyl.

7. The compound according to claim 1, where R2is heteroaryl or (C1-C6)alkylglycerol.

8. The connection according to claim 6 or 7, where the aryl or heteroaryl possibly substituted by 1, 2, 3, 4, or 5 groups independently selected from halogen, hydroxy, alkyl, cyanoalanine, aminoalkyl, trifloromethyl and alkoxy.

9. The compound according to any one of claims 1 to 8, wherein X represents-C(R3,R 4)N(R5)-.

10. The connection according to claim 9, where R3represents methyl and R4represents N.

11. The connection according to claim 9, where R5represents N.

12. The compound according to any one of claims 1 to 8, wherein X represents-C(O)N(R4)-.

13. The connection according to claim 9, where R4represents N.

14. The compound according to claim 1, which is:
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid cyclopropylamino;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2-ethylsulfanyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid phenylamide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (4-hydroxyphenyl)-amide;
Acetic acid 4-{[3-(4-chlorophenyl)-adamantane-1-carbonyl]-amino}-phenyl ester;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2,4-dihydroxyphenyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (3-hydroxymethyl-phenyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (4-cyanomethyl-phenyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid benzylamine;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-tert-butylbenzylamine;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-methylsulfonylbenzoyl;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carb is new acid 3,5-bis-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3-fluoro-5-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 2-fluoro-4-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3,5-differentiated;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3,4-differentiated;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3,4,5-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3-chloro-4-forbindelse;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-fluoro-3-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 2-chloro-4-forbindelse;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-chloro-3-triptoreline;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3-aminomethyl-2,4,5,6-tetrachlorobenzene;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [1-(4-chlorophenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [1-(4-bromophenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-methanesulfonanilide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-dimethylaminobenzene;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 4-cryptomaterial;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3-cryptomaterial;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid 3,4-dihydroxybenzylamine;
3-(4-Chlorophenyl)-adamantane-1-carbon is th acid penetrated;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(4-forfinal)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(4-bromophenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(4-hydroxyphenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(4-methoxyphenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(3-bromo-4-methoxyphenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(3,4-dihydroxyphenyl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2-benzo[1,3]dioxol-5-retil)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (3-phenylpropyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (1-methylpiperidin-4-yl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (4-methylpiperazin-1-yl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (3-tert-butylaminoethyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (3-pyrrolidin-1-ylpropyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [3-(2-oxopyrrolidin-1-yl)-propyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [2-(1-methylpyrrolidine-2-yl)-ethyl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2-morpholine-4-retil)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2-piperazine-1-retil)-amide;
3-(4-Forfinal)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)-amide;
3-(4-Harfe who yl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2-pyridine-4-retil)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (3-imidazol-1-ylpropyl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (2-methyl-1H-indol-5-yl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (1H-tetrazol-5-yl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (9-ethyl-N-carbazole-3-yl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid [4-(4-chlorophenyl)-thiazol-2-yl]-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid benzothiazol-2-alamid;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (5-chloro-benzooxazol-2-yl)-amide;
3-(4-Chlorophenyl)-adamantane-1-carboxylic acid (N-purine-6-yl)-amide;
4-{[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-amino}-phenol;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(4-trifloromethyl)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(2-fluoro-4-trifloromethyl)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(4-fluoro-3-trifloromethyl)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(4-cryptomaterial)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(1-methylpiperidin-4-yl)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(4-methylpiperazin-1-yl)-amine;
N-tert-Butyl-N'-[3-(4-chlorophenyl)-adamantane-1-ylmethyl]-propane-1,3-diamine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(3-pyrrolidin-1-ylpropyl)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-[2-(1-methylpyrrolidine-2-yl)-this is l]-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(2-morpholine-4-retil)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-pyridine-4-ylmethylamino;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-(9-ethyl-N-carbazole-3-yl)-amine;
[3-(4-Chlorophenyl)-adamantane-1-ylmethyl]-[5-(4-chlorophenyl)-thiazol-2-yl]-amine;
Phenyl-[1-(3-phenylalamine-1-yl)-ethyl]-amine;
{1-[3-(4-Forfinal)-adamantane-1-yl]-ethyl}-phenylamine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-phenylamine;
Benzyl-{1-(3-phenylalamine-1-yl)-ethyl}-amine;
Benzyl-{1-[3-(4-forfinal)-adamantane-1-yl]-ethyl}-amine;
Benzyl-{1-[3-(4-chlorophenyl)-adamantane-1-yl]-ethyl}-amine;
(4-tert-Butylbenzyl)-{1-[3-(4-chlorophenyl)-adamantane-1-yl]-ethyl}-amine;
[1-(4-Bromophenyl)-ethyl]-{1-[3-(4-chlorophenyl)-adamantane-1-yl]-ethyl}-amine;
[2-(4-Bromophenyl)-ethyl]-{1-[3-(4-chlorophenyl)-adamantane-1-yl]-ethyl}-amine;
(1 Methylpiperidin-4-yl)-[1-(3-phenylalamine-1-yl)-ethyl]-amine;
{1-[3-(4-Forfinal)-adamantane-1-yl]-ethyl}-(1-methylpiperidin-4-yl)-amine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(1-methylpiperidin-4-yl)-amine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(4-methylpiperazin-1-yl)-amine;
{1-[3-(Phenyl)-adamantane-1-yl]-ethyl}-pyridine-4-ylmethylamino;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(6-chloropyridin-3-ylmethyl)-amine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(2-pyridin-4-retil)-amine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(3H-imidazol-4-ylmethyl)-amine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(2-methyl-1H-indol-5-yl)-amine;br/> {1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(9-ethyl-N-carbazole-3-yl)-amine;
{1-[3-(4-Chlorophenyl)-adamantane-1-yl]-ethyl}-(9-ethyl-N-carbazole-3-ylmethyl)-amine;
(4-Bromothiophene-2-ylmethyl)-{1-[3-(4-chlorophenyl)-adamantane-1-yl]-ethyl}-amine;
or their pharmaceutically acceptable salts.

15. Pharmaceutical composition having the ability to inhibit sphingosine containing an effective amount of a compound according to any one of claim 1 to 14, or its pharmaceutically acceptable salt in combination with a pharmaceutically acceptable carrier medium or auxiliary agent.

16. Method of inhibiting sphingosine, including the introduction of an effective amount of a compound according to any one of claims 1 to 14 or its pharmaceutically acceptable salt or composition according to item 15.

17. The method of treatment of a disease selected from breast cancer, diabetic retinopathy, arthritis and colitis, including the introduction of a therapeutically effective amount of a compound or salt according to any one of claims 1 to 14 or a composition according to § 15.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: nucleic base (e.g. uracil, cytosine, adenine, guanine, hypoxanthine, xanthine or similar) reacts with perfluoroalkyl halide in the presence of sulphoxide, peroxide and an iron compound to obtain a perfluoroalkyl-substituted nucleic base.

EFFECT: high cost effectiveness as an intermediate compound for producing medicinal agents.

15 cl, 6 tbl

Chemical compounds // 2405780

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I): , in which: R1 and R2 are independently specified from hydrogen, C1-6alkyl, C1-6alkoxy and cyclopropyl; X1, X2 and X3 independently represent =N- or =CR10; R3 and R10 are independently specified from hydrogen, halogen, nitro, cyano, amino, carboxy, carbamoyl, C1-6alkyl, N-(C1-6alkyl)amino, N,N(C1-6alkyl)2amino, C1-6alkanoylamino, C1-6alkoxycarbonyl; R4 represents hydrogen; R5 and R6 are independently specified from hydrogen, hydroxy and C1-6alkyl where R5 and R6 independently can be optionally substituted in carbon atom with one or more R16 where R16 represents hydroxy; A represents a single link or C1-2alkylene; where specified C1-2alkylene can be optionally substituted with one or more R18; the ring C represents a saturated, partially saturated or unsaturated mono- or bicyclic ring containing 5 or 6 atoms in which at least one atom can be specified from nitrogen, sulphur or oxygen which can be linked with carbon or nitrogen atom where the -CH2- group can be optionally substituted with -C(O)- and ring sulphur atom can be optionally oxidised to produce S-oxide; R7 is specified from halogen and C1-6alkyl where R7 can be optionally substituted in carbon atom with halogen; n is equal to 0.1 or 2; where R7 values can be equal or different; and R18 is independently specified from halogen and hydroxy; or its pharmaceutically acceptable salt. Also the invention refers to their pharmaceutical compositions and methods for preparation and application thereof for cancer treatment.

EFFECT: preparation of new compounds which can find application for cancer treatment.

23 cl, 96 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I in free form or in form of pharmaceutically acceptable salt, which possess properties of adenosine receptor A2A agonists. In formula I , R1 represents (C1-C8)alkylcarbonyl, (C3-C8)cycloalkylcarbonyl, -SO2(C1-C8)alkyl, phenyl(C1-C4)alkylcarbonyl or -(C=O)-C(=O)-NH(C1-C8)alkyl, optionally substituted with R4; R2 represents H or (C1-C8)alkyl, optionally substituted with (C6-C10)aryl; R3 represents halogen or(C2-C8)alkinyl, or R3 stands for aminogroup, optionally substituted with (C3-C8)cycloalkyl, optionally substituted with amino, or R3 represents (C1-C8)alkylaminogroup, optionally substituted with hydroxy, phenyl or R5, or R3 stands for R6, optionally substituted with amino or -NH-C(=O)-NH-R7, or R3 stands for -NH-R6, optionally substituted with -NH-C(=O)-NH-R7, or R3 stands for (C1-C8)alkylaminocarbonyl, optionally substituted with. -NH-C(=O)-NH-R8; R4, R5 and R6 represent independently 5- or 6-member heterocyclic ring, which contains one-two N ring heteroatoms, optionally substituted with amino or (C1-C8)alkyl; and R7 and R8 represent independently 5- or 6-member heterocyclic ring, which contains one-two ring heteroatoms selected from N and S, and is optionally substitutedf with halogen, (C1-C8)alkylsulfonyl or 5- or 6-member aromatic heterocyclic ring, which contains one N ring heteroatom. Invention also relates to pharmaceutical composition and to application of said compounds for treatment of states, mediated by activation of adenosine receptor A2A.

EFFECT: obtaining composition, which possesses properties of adenosine receptor A2A agonists.

10 cl, 3 tbl, 80 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel purine derivatives of general formula I in free form or in form of a pharmaceutically acceptable salt which have A2A agonist properties. In formula I , R1 denotes a N-bonded 5-6-member heterocyclic group containing 1-4 nitrogen atoms in the ring, which can be optionally substituted with oxo, phenyl or C1-8-alkyl, optionally substituted with hydroxy; R2 is hydrogen or C1-C8-alkyl, optionally substituted with hydroxy or 1-2 phenyls possibly substituted with hydroxy or C1-C8-alkoxy; R3 is C2-C8-alkynyl or C1-C8-alkoxycarbonyl, or R3 is amino substituted with C3-C8-cycloalkyl, optionally substituted with amino, hydroxy, benzyloxy or NH-C(=O)-NH-R6, or R3 is amino substituted with R4, -R4-benzyl or C5-C10-mono- or bicarbocyclic group, optionally substituted with hydroxy or C1-C8-alkoxycarbonyl, or R3 is aminocarbonyl optionally substituted with R5, or R3 is C1-C8-alkylamino optionally substituted with hydroxy, R5, NH-C(=O)-C1-C8-alkyl, -MH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6 or phenyl, optionally substituted with phenyloxy, or R3 is a N-bonded 5-member heterocyclic group containing 1 nitrogen atom in the ring which may optionally be substituted with amino, C1-C8-alkylamino, di(C1-C8-alkyl)amino and other groups.

EFFECT: compounds can be useful in treating conditions mediated by activation of the adenosine A2A receptor, especially inflammatory or obstructive respiratory tract diseases.

9 cl, 5 tbl, 161 ex

FIELD: chemistry.

SUBSTANCE: in compounds of formula (I) , Q is: (IIa) or (IIb) , R1 is chosen from a group which consists of carboxylic aryl and carboxylic aryl which is substituted with substitute(s) independently chosen from a group which consists of halogen, cyano, nitro, C1-10alkyl, C1-10alkyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-9alkoxy, C1-9alkoxy which is substituted with substitute(s) independently chosen from a group which consists of halogen, mono-C1-5alkylamino, and heterocyclyl or heterocyclyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-5alkyl; R2 is C1-5alkyl, C1-5alkyl which is substituted with halogen, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, -N(R2a)(R2b); where R2a and R2b are each independently hydrogen, C1-5alkyl or C1-5alkyl, substituted with substitute(s) independently chosen from a group which consists of hydroxyl, carboxylic aryl; L represents formula (IIIa); , where R3 and R4 are each hydrogen; A is a single bond, and B is a single bond or -CH2-; Z1, Z3, and Z4 are each independently hydrogen, halogen, C1-5alkyl, C1-5alkyl, substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Z2 is hydrogen, C1-5alkyl, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Y is -C(O)NH-, -C(O)-, -C(S)NH-, -C(O)O- or -CH2-; where carboxylic aryl is phenyl; heterocyclyl is 1H-indolyl, 9H- xanthenyl, benzo[1,3]dioxolyl, furyl, imidazolyl, isoxazolyl, morpholinyl, piperazinyl, pyridyl, pyrrolidyl; halogen is fluorine, chlorine, bromine or iodine. The invention also relates to a pharmaceutical composition.

EFFECT: compounds can be used for treating central nervous system diseases, and for improving memory functioning, sleep, awakening, diabetes.

16 cl, 8 dwg, 4 tbl, 525 ex

Comt inhibitors // 2354655

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula I where R1 stands for H, CN, halogen, -COR2, -S(O)xR2, C1-C12alkyl, C2-C12alkenyl, C3-C8dicloalkyl, aryl group, heteroaryl group standing for 5- or 6-merous aromatic mono- or bicyclic heterocyclic group with 1-2 heteroatoms, chosen of N or S, C3-C8cycloalkyl-(C1-C3)alkyl or group aril-(C1-C3)alkyl; alkyl, alkenyl, cycloalkyl, aryl and heteroaryl groups can be optionally substituted with halogen, C1-C6alkyl, group-COR2; R2 stands for -N(R3,R3'), C1-C6alkyl, C3-C8cycloalkyl, aryl, heteroaryl which stands for 5- or 6-merous aromatic mono- or bicyclic heterocyclic group with 1-2 heteroatoms chosen of N, C3-C8cycloalkyl-(C1-C3) alkyl or aril-(C1-C3)alkyl; C1-C6alkyl, C3-C8cycloalkyl, aryl, heteroaryl can be optionally substituted with halogen, C1-C6alkyl; R3 and R3' independently stands for hydrogen or (C1-C3)alkyl; x stands for 0, 1 or 2; and also to their esters, hydrolyzed in physiological environment, and to their pharmaceutically acceptable salts. The invention also concerns a medical product.

EFFECT: production of new biologically active compounds active as COMT inhibitor.

17 cl, 19 ex, 1 tbl

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides novel N6-substituted adenine-based heterocyclic compounds depicted by general formula I: , for which meanings of radicals are presented in description, and pharmaceutically acceptable salts thereof manifesting anticancer, mitotic, immunosuppressive, and antiaging activities for vegetable, animal, and human cells, and methods for preparation thereof. Included are also pharmaceutical compositions, cosmetic preparations, and growth regulators, which contain indicated derivatives as active components. Application of indicated derivatives for preparing therapeutical preparations, and cosmetic preparations are also described.

EFFECT: expanded synthetic possibilities in adenine series and increased choice of various biologically active agents.

10 cl, 10 dwg, 9 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): or their pharmaceutically acceptable salts wherein rings A and B represent optionally substituted benzene rings; R1 represents alkyl, hydroxyl, thiol, carbonyl, sulfinyl, unsubstituted or substituted sulfonyl group and others; R2 represents hydrogen atom, hydroxyl, amino-group, alkyl, unsubstituted or substituted carbonyl group or halogen atom; Z represents oxygen atom or group -N(R3)- wherein R3 and R4 represent hydrogen atom or alkyl group under condition that N-acetyl-1-benzyloxycarbonyl-2-phenyl-4-piperidineamine is excluded. Compounds of the formula (I) or their salts possess antagonistic activity with respect to tachykinin NK1-receptors and can be used in medicine in treatment and prophylaxis of inflammatory, allergic diseases, pain, migraine, diseases of central nervous system, digestive organs and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of treatment.

18 cl, 138 tbl, 527 ex

The invention relates to the derivatives of purine, which has antiviral activity against human cytomegalovirus and human immunodeficiency virus type 1, of General formula:

where n = 0 to 4; m = 0 to 3; R1= N, HE or NH2; R2= HE, NH2, acetylamino or benzoylamine; R3= H or lower alkyl (C1-C4; R4= H, lower alkyl (C1-C4or phenyl; X = CH2, O, S, NH or C(O)O; and Y = CH2, CH=CH, C(O), or ordinary communication; Ar = phenyl, pyridyl, naphthyl or substituted phenyl of the formula

where independently R5-R9= alkyl1-C8cycloalkyl C5-C6, 1-substituted, allyl, phenyl, benzyl, F, Cl, Br, J, trifluoromethyl, alkoxy, C1-C5phenoxy, benzyloxy, benzoyloxy, cyano, carboxy, acetyl, or nitro, antiviral effect of the most active compounds against human cytomegalovirus in vitro manifests itself in concentrations of 0.01-0,0005M and is characterized by selectivity 1-400 thousand

The invention relates to new compounds of General formulas I, II, III

< / BR>
or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,

-CHR2SR12, -C(S)R2or-C(O)R2N-ethyl-2,2,2-triptorelin; G is oxygen, sulfur, NH, NH3hydrogen, methoxy, ethoxy, triptoreline, methyl, ethyl, dimethoxy, NH2, NHCH3N(CH3)2or trifluoromethyl; Y Is N; Z is NH, O, S, -N(C1-C2alkyl) or-C(R13R14), where R13and R14independently of one another represent hydrogen, trifluoromethyl or methyl, or one of the elements of R13and R14is cyano and the other is hydrogen or stands; R1- C1-C6alkyl which may be optionally substituted by one or two substituents R8independently from each other selected from the group comprising hydroxy, fluorine, chlorine, bromine, iodine, CF3C1-C4alkoxy, -O-CO-(C1-C4alkyl), where (C1-C2- C1-C12alkyl, aryl or -(C1-C4alkylene)aryl, where aryl is phenyl, naphthyl; R3is methyl, ethyl, fluorine, chlorine, bromine, iodine, cyano, methoxy, OCF3, methylthio, methylsulphonyl, CH2HE or CH2OCH3; R4is hydrogen, C1-C4alkyl, fluorine, chlorine, bromine, iodine, C1-C4alkoxy, triptoreline, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -CF3, amino, nitro, -NH(C1-C4alkyl), -N(CH3)2, -NHCOCH3, -NHCONHCH3, hydroxy, -CO(C1-C4alkyl), -Cho, COOH, cyano, or-COO(C1-C4alkyl), where C1-C4the alkyl may be substituted by one Deputy chosen from the group comprising hydroxy, amino, -NHCOCH3, -NH(C1-C2alkyl), -N(C1-C2alkyl)2, fluorine, chlorine, cyano, nitro; R5is phenyl, naphthyl, pyridyl, pyrimidyl, where each of the above groups R5substituted with one to three substituents that are independently from each other selected from fluorine, chlorine, C1-C6the alkyl or C1-C6alkoxyl, or one Deputy chosen from the group comprising hydroxy, iodine, bromine, formyl, cyano, nitro, trifluoromethyl, amino, -(C1-C6these groups of R5may be optionally substituted with one hydroxy-group; R6is hydrogen or C1-C6alkyl; R7is hydrogen, methyl; R11is hydrogen, hydroxy, fluorine or methoxy; R12is hydrogen or C1-C4alkyl, and R16and R17independently of one another represent hydrogen, hydroxy, methyl, ethyl, methoxy or ethoxy, except that both R16and R17cannot both be methoxy or ethoxy; or R16and R17together form oxo (=O) group; provided that if G is an atom of oxygen, sulfur, NH or NCH3he is joined by a double bond to a five-membered ring of the formula III, and further provided that R6is absent when the nitrogen atom to which it is linked, is attached by a double bond to an adjacent carbon atom in the ring

FIELD: chemistry.

SUBSTANCE: compound is a matrix metalloproteinase or aggrecanase. The invention also relates to a pharmaceutical composition based on said compounds and a method of treating osteoarthritis, (I), where W is -C(O)-; R1 is bisphenyl, possibly containing one or more substitutes R5 and R6; and if R1 contains one or more substitutes R5 and R6, the substitutes can be identical or different; R2 is hydrogen; R3 is -CO2H, -CONHOH, -CONHR7 or -COOR7; R4 is -CONR9R10; m equals 0. The values of substitutes R5-R7, R9, R10 are as described in the claim.

EFFECT: compounds have the capacity to modulate metalloproteinase activity.

18 cl, 40 ex, 18 dwg, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds selected from a group comprising piperazine compounds of formula I: , where X is -CH2- or a bond; n equals 1; R1 is alkyl; cycloakyl; hydroxyethyl; benzo[1,3]dioxolyl; phenyl, which can be mono-substituted with a halide, alkyl, alkoxy, -CF3 or alkylcarbonyl; or phenyl which is di- or tri-substituted with substitutes independently selected from alkyl and halide; pyridyl which can be mono-substituted with a halide, alkyl or -CF3; furanyl which can be mono-substituted with methyl, hydroxymethyl or bromine, or furanyl which is disubstituted with an alkyl; thienyl which can be mono-substituted with methyl or chromium; pyrimidinyl; isoquinolinyl; benzhydryl; imidazolyl optionally mono-substituted with an alkyl; or thiazolyl; or X is -C(=O)- and R1 is hydrogen; R2 is indolyl, imidazolyl optionally mono-substituted with alkyl; phenyl which can be mono-substituted with a halide, alkyl, hydroxy or cyano, or phenyl which is disubstituted with a halide; pyridyl; benzothienyl; thiazolyl or thienyl; R3 is indolyl, pyridyl which can be mono-substituted with alkoxy, alkoxyalkoxy, NR31R32, morpholine, piperadine, oxopiperidinyl, oxopyrrolidinyl, pyridyl or phenyl; or phenyl which is mono-substituted with phenyl, pyridyl, alkyl, alkoxy, dialkylamino, morpholine, N-benzyl-N-alkylamino, (dialkylamino)alkoxy, phenylalkoxy or tetrahydroisoquinolinyl; or R3 denotes the group: , where Z is phenyl or pyridyl; R31 is 2-C1-C5alkoxyethyl, phenyl, pyridyl, phenylalkyl, hydroxyalkylcarbonyl, alkylcarbonyl, cycloalkylcarbonyl or phenylcarbonyl; R32 is hydrogen or methyl; R35 is alkyl, alkylcarbonyl, phenyl, pyridyl or pyrimidinyl; and R4 is phenyl-CH=CH-, where the phenyl can be mono-, di- or tri-substituted with substitutes independently selected from halide, alkyl, alkoxy and -CF3; or phenyl-CH2-CH2, where the phenyl is disubstituted with -CF3; and to optically pure enantiomers thereof, mixtures of enantiomers, such as, for example, racemates, optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates, mixtures of diastereomeric racemates and mesoforms, such as salts of such compounds. The invention also relates to a pharmaceutical composition, as well as to use of compounds in any of claims 1-4.

EFFECT: obtaining novel biologically active compounds with antimalarial activity.

8 cl, 138 ex, 1 tbl

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel bioisosteres of actinonin of general formula (I) , as well as to pharmaceutically acceptable salts thereof and pharmaceutical compositions based on said compounds, with peptide deformylase (PDF) inhibitory activity, as well as to use of the compounds or pharmaceutical compositions based on said compounds to prepare medicinal agents. In general formula (I) R1 is a hydrogen atom, R2 is a hydrogen atom, (C1-C6)alkyl residue, hetero(C1-C6)alkylphenyl residue, where the heteroatom is sulphur, R3 is a hydrogen atom, R4 is (C1-C6)alkyl residue, (C3-C7)cycloalkyl residue, R6 is a hydrogen atom, n is 1, 2 or 3. Values of substitute R5 are given in the formula of invention.

EFFECT: new compounds have useful biological activity.

8 cl, 1 ex

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to compound of formula (I) in which m represents integer number, equal 1 or 2; R1 represents group, selected, in particular from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, naphtyl, chinolinyl, isochinolinyl, benzisoxazolyl, tienopyridinyl, said group is possibly substituted with one or several groups of R3, similar or different from each other or by group R4, R2 represents group of general formula CHR5CONHR6, R3 represents halogen atom or one of the following groups: piano, nitro, C1-6-alkyl, C1-6-alkoxy, C1-6-trifluoralkyl, C1-6-trifluoralkoxy, benzyloxy, phenyloxy, R4 represents group, selected, in particular from phenyl, benzofuranyl, naphtyl; one orseveral groups R4 can by substituted with one or several groups R3, similar or different from each other; R5 represents hydrogen atom or C1-3-akyl group; R6 represents hydrogen atom or alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl -C1-3-alkylene group; as base, salts of binding of acid, hydrate or solvate. Also invention relates to method of obtaining compound of formula I, its use as medicine and to based on it pharmacological composition.

EFFECT: novel derivatives of 1-pyperazine and 1-homopyperazincarboxilates, useful for prevention or treatment of pathology, in which endogen cannabinoids and/or any other substrates, metabolised by ferment FAAH, participate.

12 cl, 3 tbl, 11 ex

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic

The invention relates to new derivatives of benzodioxole, benzofuran, dihydrobenzofuran and benzodioxane or their pharmaceutically acceptable solvate of General formula I

< / BR>
where Q1and Q2every means independently hydrogen or halogen;

X is CH2CH or oxygen;

Y represents CR3, CR3R4or (CH2)nwith n = 1-4;

Z denotes CH2CH or oxygen;

R means hydrogen, halogen or alkyl WITH1-4in both cases;

m denotes 1 or 2;

R1means1-6-alkyl, C3-6-cycloalkyl,1-3-haloalkyl,1-6-alkylamino,2-6alkenyl,1-4-alkoxy(C1-4)alkyl, C1-C4-alkylthio(C1-4)alkyl or triptorelin-C1-4;

R2means hydrogen, halogen or C1-4-alkyl; and

R3and R4each independently mean hydrogen or C1-4-alkyl,

containing pharmaceutical compositions for the treatment of sleep disorders, and disorders associated with disturbance of circadian rhythms

The invention relates to chemical agents regulating the growth and development of crops specifically for use as a growth promoter and herbicide new compounds of the formula

ClOCH2COOHH2N< / BR>
The claimed connection, its physico-chemical characteristics, method of production and application are not described in literature

The invention relates to new chemical compound is 5-amino-2-methylbenzothiazole-1,3(2-methoxy-3,6-sodium dichloro, benzoate formula

OHH2Nwhich can find application in agriculture as a herbicide

The invention relates to chemical means of plant protection, namely the compound of the formula

CH3OOCCOOHH2Nhave a weed-killing activity
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