Heterocyclic aspartyl protease inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds being aspartyl protease inhibitors applicable for treating cardiovascular, neurodegenerative disorders and fungal infection of formula , wherein W represents -C(=O)-; X represents -NH-; U represents -C(R6)(R7)-; R1 represents methyl, R2, R3 and R6 represent H, R4 and R7 represent optionally substituted phenyl, as well as tautomers and pharmaceutically acceptable salts thereof.

EFFECT: there are presented new effective aspartyl protease inhibitors specified in rennin, cathepsin D, BACE-1, for treating cardiovascular diseases, cognitive and neurodegenerative diseases, as well as fungal infections.

67 cl, 1 tbl, 4393 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from the group consisting of:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

2. The compound according to claim 1 where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glicerio the veil, hemisulfate, heptanoate and hexanoate.

3. The compound according to claim 1 where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

4. The compound according to claim 1 where the pharmaceutically acceptable salt of the compounds is tosylate salt.

5. A compound selected from the group consisting of:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

6. The compound according to claim 5, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate is, heptanoate and hexanoate.

7. The compound according to claim 5, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

8. The compound according to claim 5, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

9. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

10. The connection according to claim 9, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

11. The connection according to claim 9, where the pharmaceutically acceptable salt of the compounds or asanoha tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

12. The connection according to claim 9, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

13. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

14. The connection indicated in paragraph 13, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

15. The connection indicated in paragraph 13, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, matilal the veil, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

16. The connection indicated in paragraph 13, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

17. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

18. The connection 17, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

19. The connection 17, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

20. The connection 17, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

21. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

22. Connection item 21, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

23. Connection item 21, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate

24. Connection item 21, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

25. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

26. Connection A.25, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

27. Connection A.25, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

28. Connection A.25, where the pharmaceutically acceptable salt of the compounds is tosilate the Yu salt.

29. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

30. The connection clause 29, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

31. The connection clause 29, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

32. The connection clause 29, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

33. The compound having the formula:

or tautomer, or pharmaceutically reception who will be the salt of the compounds or specific tautomer.

34. Connection p, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

35. Connection PSS, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

36. Connection p, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

37. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

38. The connection clause 37, where the pharmaceutically acceptable salt of the compounds or specific tautomer in baraut from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

39. The connection clause 37, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

40. The connection clause 37, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

41. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

42. The connection at paragraph 41, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, qi is rata, camphorata, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

43. The connection at paragraph 41, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

44. The connection at paragraph 41, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

45. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

46. Connection § 45, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata of glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

47. Connection § 45, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

48. Connection § 45, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

49. The compound having the formula:

or tautomer, or pharmaceutically acceptable salt of the compounds or specific tautomer.

50. Connection § 49, where the pharmaceutically acceptable salt of the compounds or specific tautomer choose from:
acetate, adipate, alginate, ascorbate, aspartate, benzoate, bansilalpet, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, aconsultant, fumarata, glucoheptonate, glycerol, hemisulfate, heptanoate and hexanoate.

51. Connection § 49, where the pharmaceutically als the salt of the compounds or specific tautomer choose from:
hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic, lactate, maleate, methanesulfonate, methyl sulfate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, salicylate, succinate, sulfate, sulfonate, tartrate, thiocyanate, tosilata and undecanoate.

52. Connection § 49, where the pharmaceutically acceptable salt of the compounds is tosylate salt.

53. Pharmaceutical composition having the properties of an inhibitor against aspartyl proteases person selected from renin, cathepsin D, BOB-1, containing an effective amount of a compound according to any one of claims 1 to, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45 and 49, or tautomer, or pharmaceutically acceptable salts of the compounds or specific tautomer and a pharmaceutically acceptable carrier.

54. The use of compounds according to any one of claims 1 to, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45 and 49, or tautomer, or pharmaceutically acceptable salts of the compounds or specific tautomer for the preparation of a medicine for inhibiting aspartyl proteases person selected from renin, cathepsin D, VASYA-1.

55. The use of compounds according to any one of claims 1 to, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45 and 49, or tautomer, or pharmaceutically acceptable salts of the specified connection is in or specified tautomer for the preparation of drugs for the treatment of cardiovascular diseases, cognitive and neurodegenerative diseases or fungal infection.

56. The application of § 55, where treatment is subjected to a cognitive or neurodegenerative disease.

57. Use p, where cognitive or neurodegenerative disease is Alzheimer's disease.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of general formula (I): wherein m and n independently represent 0 or 1; G and E represent oxygen, R1 and R2 together with a carbon atom whereto attached form a heterocycle including one or two heteroatoms specified in oxygen, sulphur, -S(O)-, -S(O)2-, -N=, -N(R5)-; one or more carbon atoms in the above heterocycle are optionally substituted by one or more identical or different substitutes specified among the substitutes R4; R3 represents alkoxy or halogenoxy; R4 represents hydrogen, alkyl or halogen; R5 represents hydrogen, alkyl carbonyl, alkoxy carbonyl or alkyl sulphonyl; X represents a bond, -CH2- or -NH-; A represents phenyl, pyridyl, pyrazynyl or quinolyl optionally substituted by one or more identical or different substitutes specified among the substitutes R4; or pharmaceutically acceptable salts, hydrates, N-oxides or salvates thereof.

EFFECT: invention also refers to the pharmaceutical composition of the above compounds as the phosphodiesterase PDE4 inhibitor for treating, eg skin diseases.

19 cl, 2 tbl, 32 ex

FIELD: chemistry.

SUBSTANCE: invention relates to spirocyclic cyclohexane derivatives of formula I where values of R1-10 are given in claim 1.

EFFECT: compounds have affinity for the ORL1 receptor, which enables use thereof in producing a medicinal agent for treating pain, especially sharp, neuropathic or chronic pain.

12 cl, 1 tbl, 52 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel spirocyclic cyclohexane derivatives of formula I: , where: R1 and R2 together form a ring and are -CH2CH2CH2-; R3 denotes a saturated, branched or straight, unsubstituted C1-5-alkyl; unsubstituted or monosubstituted with F, Cl, Br, I phenyl; 5-member heteroaryl containing sulphur as a heteroatom; unsubstituted or monosubstituted with F, Cl, Br, I phenyl, attached through a C1-3-alkyl group; R5 denotes H; R6 denotes H, F, Cl; R7, R8, R9 and R10 independently denote H, F, Cl, Br, I; X denotes O, NR17; R17 denotes H, COR12; R12 denotes H, unsaturated, branched or straight, unsubstituted or phenyl-substituted C1-5-alkyl; in form of a racemate; enantiomers, diastereomers, mixtures of enantiomers or diastereomers, or a separate enantiomer or diastereomer; bases and/or salts of physiologically compatible acids or cations.

EFFECT: compounds have binding action on the ORL1 receptor and the µ-opioid receptor, which enables their use to treat various diseases.

12 cl, 11 ex

FIELD: chemistry.

SUBSTANCE: described are spirocyclic derivatives of cyclohexane of general formula . Values of radicals are given in the formula of invention. The compounds have affinity to the ORL1 receptor and can be used for treating abstinence syndrome (withdrawal syndrome) and pain. Also described is a medicinal agent and use of formula (I) compounds for preparing respective medicinal agents.

EFFECT: increased effectiveness of using the compounds.

13 cl, 17 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

The invention relates to new spirochetes formula I

< / BR>
where Ar is phenyl, substituted phenyl where the substituents are: alkoxy, alkyl, alkoxyalkyl, phenoxy, halogen, pyridyloxy, alkoxyalkane, halogenfree; R1- H; R2- H1-C4alkyl; W represents O or one or more1-C4alkyl fragments; Y is independently one or more members of the group consisting of H2, SR3, alkoxy; R3- H, alkyl; Z is a carbocyclic or heterocyclic Spiro-fragment with a 3-7 member ring system, where the heterocyclic fragment includes 2 oxygen atom or sulfur, or one nitrogen atom and spirits may be unsubstituted or substituted by hydroxy, C1-C4the alkyl, benzyloxy; n=1-3; optical isomers, diastereomers or enantiomers or pharmaceutically acceptable salts

The invention relates to salts sulfoxides derived, namely the hydrochloride or the fumarate of 1-{ 2-[(2R)-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholine-2-yl] ethyl} Spiro[benzo(C)thiophene-1(3H),4'-piperidine]-(2S)-oxide, which have a good absorption when taken orally and demonstrate excellent antagonistic activity as receptor NK1and receptor NK2

The invention relates to new derivatives of pyrrolidinone possessing biological activity, in particular derivatives of 1H-3-aryl-pyrrolidin-2,4-dione

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to indolyl-substituted derivatives of thiadiazinones prepared from oxamic acid thiohydrazide of general formula: , wherein R represents H; R1 represents pyridinyl; phenyl substituted by alkyl C1-C5, Hal, CF3; R2 represents H; alkyl C1-C5; -CH2COOR4; benzyl substituted by Hal, OR4; benzoyl substituted by Hal, OR4, while R4 represents unsubstituted alkyl C1-C4.

EFFECT: there are prepared new compound which can find application in medicine for developing the therapeutic agent possessing pathogenic bacteria inhibitory activity.

2 cl, 2 dwg, 2 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel heterocyclic nitrogen- and oxygen-containing compounds having insecticidal activity. In formulae (A) (B) (C) (D) R1 is a 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/ or sulphur atom, a halogen-substituted 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/or sulphur atom, a substituted or unsubstituted phenyl, where the substitutes are one or more groups selected from a group consisting of halogen atoms, C1-4 halogen alkyl or C1-4 chloroalkoxyl; R5, R6, R7, R8 and R9 are H, saturated or unsaturated C1-4 alkyl, halogen atom, saturated or unsaturated C1-4 alkoxyl, saturated C1-4 halogenalkoxyl, C1-4 alkylcarbonyl, C1-8 alkyl ester, C1-4 alkylsulphonyl, phenyl, benzyl or trifluoromethane sulphonyl ether group; Y is nitro, cyano, trifluoromethyl, trifluoroacetyl or trifluoromethylsuphonyl. Values of radicals R, R2-R4 are given in the claim.

EFFECT: invention also relates to an agrochemical composition containing said compounds, use of the agrochemical composition in pest control and a method of producing said compounds.

12 cl, 7 tbl, 36 ex

Azole compounds // 2493154

FIELD: chemistry.

SUBSTANCE: invention relates to compounds which are pyridin-3-yl 4-(3-phenyl-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-[3-(4-fluoromethyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-[5-(4-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate, 2,6-dimethylpyridin-3-yl 4-[5-(3,4-difluorophenyl)-1,2,4-oxadiazol-3-yl]piperidine-1-carboxylate, 2-methylpyridin-3-yl 4-[3-(2-fluorophenyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-(3-phenyl-1H-pyrazol-1-yl)piperidine-1-carboxylate, 2-methylpyridin-3-yl 4-[5-(3-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate and 6-methylpyridin-3-yl 4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate or to a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds, having inhibiting effect on fatty acid amide hydrolase (FAAH).

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine for treating neuropathic pain.

13 cl, 38 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound, which is N3-1H-indol-5-yl-5-pyridin-4-ylpyrazine-2,3-diamine, or a pharmaceutically acceptable salt thereof, which can act as inhibitors of protein kinase, especially FLT3 tyrosine kinase. The invention also relates to a pharmaceutical composition which contains said compound in combination with another molecularly directed (target) agent, which is a traditional cytotoxic agent or a compound used after chemotherapy, supporting therapy targeted on stem cells and in case of MLL rearrangement acute lymphoblastic leukaemia in children.

EFFECT: obtaining a novel compound which can be used in medicine for preventing or treating haematological malignant growths such as AML, MLL, T-ALL, B-ALL and CMML, myeloproliferative diseases, autoimmune diseases and skin diseases, such as psoriasis and atopic dermatitis.

16 cl, 2 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to antibacterial compounds of formula (I) , where one or two of U, V, W and X represent N, the remaining ones represent CH or, in case X, can also represent CRa, where Ra represents fluorine; R1 represents alcoxygroup, halogen or cyanogroup; R2 represents H, CH2OH, CH2N3, CH2NH2, alkylcarbonylaminomethyl or triazol-1-ylmethyl; R3 represents H or, when n=1, R3 can also represent OH, NH2, NHCOR6 or triazol-1-yl; A represents CR4; K represents O, NH, OCH2, NHCO, NHCH2; CH2NH5 CH2CH2, CH=CH, CHOHCHOH or CHR5; R3 represents H or together with R5 forms bond, or R4 can also represent OH, when K is not O, NH, OCH2 or NHCO; R5 represents OH or together with R4 forms bond; R6 represents alkyl; m=0 or 1 and n=0 or 1; and G is specified in i.1 of the formula; and to salt of such compound.

EFFECT: obtaining antibacterial compounds.

19 cl, 1 tbl, 44 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel pyridine derivatives pyridine1-A-pyridine2 of formula (1), where pyridine1 represents

, , or , ,

where asterisks stand for bond, which contains pyridine1 ring with A; R1 represents C1-5alkyl, C1-4alkoxygroup, C3-6-cycloalkyl, hydroxymethyl or NR1aR1b, R1a represents C1-4alkyl; R1b represents hydrogen or C1-3alkyl; or R1a and R1b, together with nitrogen atom, which is bound to pyridine, form pyrrolidine ring; R2 represents hydrogen or C1-4alkyl, or in case, when R1 represents C1-5alkyl or C3-6-cycloalkyl, R2 can additionally represent methoxygroup; R3 represents C1-4alkyl, C1-4alkoxygroup, C3-6-cycloalkyl or NR3aR3b; R3a represents C1-4alkyl; R3b represents hydrogen or C1-3alkyl; R4 represents C1-4alkyl or hydrogen; R5 represents C1-5alkyl, methoxygroup or NR5aR5b; and R6 represents C1-2alkyl; R5a represents C1-4alkyl; R5 represents hydrogen or C1-3alkyl; or R5 represents C1-2alkyl or methoxygroup; and R6 represents C1-5alkyl or NR6aR6b; R6a represents C1-4alkyl; R6b represents hydrogen or C1-3alkyl; R7 represents C1-5alkyl; R8 represents C1-2alkyl or methoxygroup; R9 represents C1-5alkyl; R10 represents C1-2alkyl; A represents

, , or ,

where asterisks stand for bond, binding pyridine1 ring with A; pyridine2 represents

, , or , ,

where asterisks stand for bond, which binds pyridine ring with A; R11 represents C1-4alkyl; C1-3alkyloxy group, hydroxymethyl or NR11aR11b; R,1a represents C1-3alkyl; R11b represents hydrogen or C1-2alkyl; R12 represents hydrogen or C1-4alkyl; R13 represents C1-4alkyl or NR13aR13b; R13a represents C1-4alkyl; R13b represents hydrogen or C1-2alkyl; R14 represents C1-2alkyl; R15 represents C1-4alkyl or NR15aR15b; and R16 represents C1-2alkyl; R15a represents C1-3alkyl; R15b represents hydrogen or C1-3alkyl; or R15 represents C1-2alkyl; and R16 represents C1-4alkyl or NR16aR16b; R16a represents C1-3alkyl; R16b represents hydrogen or C1-2alkyl; R17 represents C1-4alkyl; R18 represents C1-2alkyl or methoxygroup; R19 represents C1-4alkyl; and R20 represents C1-2alkyl; with exception of 3-(2-ethyl-4-pyridyl)-5-(2-ethyl-4-pyridyl)-1,2,4-oxadiazole; or pharmaceutically acceptable salt of such compound.

EFFECT: obtaining pyridine derivatives, which possess agonistic activity with respect to S1P1/EDG1.

15 cl, 2 tbl, 131 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are novel aminitriazole derivatives of formula (I), where A is phenyl, heterocyclyl or propan-1,3-diyl; E is *-C1-4alkyl-O-, -CH=CH- or , where asterisks stand for bond, through which binding with R1; Q- O or S occurs; R3 is hydrogen, C1-4alkyl, cyclopropyl, C1-4alkoxy-C1-4alkyl, benzyl or -CH2CH2C(O)O-tert-Bu; R1 is pyridyl or phenyl, possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, C1-4fluoroalkyl, C1-4fluoroalkoxy, di-( C1-3alkyl)amino or C1-4alkoxy-C1-2alkyl; and R2 is -CO-C1-3alkyl,-CF2-C1-3alkyl or -SO2-C1-3alkyl; or their pharmaceutically acceptable salts, pharmaceutical composition, which contains them.

EFFECT: obtaining novel compounds for treatment of inflammatory disease or Alzheimer's disease.

20 cl, 105 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula 1:

or pharmaceutically acceptable salts thereof, where values of Cy1; Cy2; L1; L2, R; R1; Rx and Ry and R2 are given in claim 1.

EFFECT: compounds are suitable for use as Raf protein kinase inhibitors.

36 cl, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to polymorphous form of compound

,

which is characterised by picture of X-ray diffraction, including discriminatory peaks approximately 7.269, 9.120, 11.038, 13.704, 14.481, 15.483, 15.870, 16.718, 17.087, 17.473, 18.224, 19.248, 19.441, 19.940, 20.441, 21.469, 21.750, 22.111, 23.319, 23.763, 24.120, 24.681, 25.754, 26.777, 28.975, 29.609, 30.073 degree 2Θ. Invention also relates to method of obtaining polymorphous form of compound (IX), which includes processing of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-ylthiazol-2-ylamino)phenyl]benzamide with methanesulfonic acid at temperature from 20 to 80°C in solvent, selected from group, which includes methanol, ethanol, acetone, diethyl ether, dioxane and their mixtures.

EFFECT: obtaining polymorphous form of compound (IX), which remains dry at 80% relative humidity and thermodynamically stable at temperatures lower than 200°C.

7 cl, 3 dwg, 4 ex

Organic compounds // 2491285

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein V is specified in -O- or a single bond; W is specified in -N(R5)C(O)-, -S(O)t- and -C(O)O-; X is specified in C(H) or N; Y is specified in S, N(H) or N(CH3); p means 0 or 2; t means 1 or 2; R1 is specified in a group consisting of hydrogen, C1-6alkyl optionally substituted by 1 or 2 halogroups, C3-7cycloalkylC1-6alkyl, 2,3-dihydro-1H-indenyl, C6arC1-6alkyl optionally substituted by one or two halogroups and heteroarylC1-6alkyl, wherein a heteroaryl fragment of the heteroarylalkyl group means 5-6-member monocyclic heteroaryl containing 1 or 2 heteroatoms independently specified in a group consisting of nitrogen optionally oxidated, oxygen and sulphur, or a heteroaryl fragment of the heteroarylalkyl group means 9-member bicyclic heteroaryl containing 1 or 2 heteroatoms independently specified in a group consisting of nitrogen, oxygen and sulphur, wherein monocyclic heteroaryl of the heteroarylalkyl group may be optionally substituted by one or two substitutes independently specified in a group consisting a halogroup, a cyanogroup, C1-6alkyl, haloC1-6alkyl and C1-6alkyl-O-C(O)-; R2 is specified in a group consisting of hydrogen, C1-6alkyl optionally substituted by phenoxy, hydroxy C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl, phenyl optionally substituted by a halogroup, haloC1-6alkyl, C6arC1-6alkyl (optionally substituted by a halogroup, haloC1-6alkyl or haloC1-6alkoxygroup), 2-oxo-imidazolidinyl, heterocyclylC1-6alkyl and heteroarylC1-6alkyl, wherein heterocyclyl of heterocyclylalkyl means 5- or 6-member monocycle containing oxygen, and wherein a heteroaryl fragment of the heteroarylalkyl group means 5-6-member monocycle containing 1-3 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, or a heteroaryl fragment of the heteroarylalkyl group means 9- or 10-member bicycle containing 1 to 2 heteroatoms specified in a group consisting of nitrogen and sulphur, wherein monocyclic heteroaryl of the heteroaryl alkyl group may be optionally substituted by 1 or 2 substitutes independently specified in a group consisting of a halogroup, C1-6alkyl, haloC1-6alkyl and phenyl optionally substituted by a halogroup; R3 is specified in a group consisting of hydrogen and alkyl; two adjacent R4 groups together with carbon atoms whereto attached can form phenyl; R5 means hydrogen; or a pharmaceutically acceptable salt thereof.

EFFECT: preparing the heterocyclic derivatives which modulate activity of stearoyl CoA desaturase, methods of using the above derivatives for modulating activity of stearoyl CoA desaturase and pharmaceutical compositions containing the above derivatives.

26 cl, 1 tbl, 153 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I , where R1 and R2 independently denote hydrogen, C3-C7cycloalkyl, C1-C6alkyl, C2-C6alkynyl, hydrogen or pyridine; or R1 and R2 together with a nitrogen atom which binds them form a pyrroline group; R3 denotes hydrogen, C1-C6halogenalkyl, C1-C6alkyl, halogen, cyano group, nitro group, C1-C4alkoxy group, phenyl, halogen-substituted phenyl, (R51)(R52)(R53)Si-(C2-C6alkynyl)-, where R51, R52, R53 independently denote halogen, cyano group, C1-C6alkyl, C2-C6alkenyl, C3-C8cycloalkyl, C5-C8cycloalkenyl, C2-C6alkynyl, C1-C6alkoxy group, benzyl or phenyl; R4 denotes hydrogen, halogen, phenyl, imidazolyl, amino group, C1-C6alkoxy group or C1-C6alkyl; R5 denotes C1-C12alkyl or a group A, where A denotes a 3-10-member monocyclic or condensed bicyclic ring system which can be aromatic, partially unsaturated or completely saturated, where said 3-10-member ring system can be mono- or polysubstituted with substitutes independently selected from a group comprising halogen, C1-C6alkyl, C1-C6halogenalkyl, C1-C6alkoxy group and C1-C6alkylthio group; R6 denotes hydrogen; and R7 denotes hydrogen or C1-C6alkyl and agronomically acceptable salts/metal complexes/metalloid complexes/isomers/structural isomers/stereoisomers. The invention also relates to methods of controlling infection of useful plants by phytopathogenic microorganisms by applying a compound of formula I onto the plants, a part thereof or place where said plants grow, as well as a composition for controlling infection by phytopathogenic microorganisms.

EFFECT: novel compounds which are suitable for use as microbiocides are obtained and described.

7 cl, 48 ex, 151 tbl

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