Derivatives copernicia possessing antibacterial activity, containing pharmaceutical composition, the method of treatment of infectious diseases, a microorganism capable of producing the above derivative, and method for producing such derivatives using this microorganism

 

The invention relates to a derivative copernicia and their pharmaceutically acceptable salts of General formula Iwhere R1represents a methyl group, R2represents a methyl group, R4represents a hydroxy-group and X represents a methylene group; R1represents a methyl group, R2represents a hydrogen atom, R4represents a hydroxy-group and X represents a methylene group; R1represents a methyl group, R2represents a methyl group, R4represents a hydrogen atom and X represents a methylene group; R1represents a hydrogen atom, R2represents a hydrogen atom, R4represents a hydroxy-group and X represents a methylene group; or R1represents a methyl group, R2represents a methyl group, R4represents a hydroxy-group and X represents a sulfur atom. The invention also relates to pharmaceutical compositions based on compounds of the formula I, the method of treatment of infectious diseases, the microorganism capable of producing the above derivative, and method for producing such derivatives with the help of this microorganism. Technical R the-break-before:always;">

Description text in facsimile form (see graphic part).

Claims

1. The compound of formula (I) or its pharmaceutically acceptable saltwhere R1represents a methyl group, R2represents a methyl group, R4represents a hydroxy-group, and X represents a methylene group; R1represents a methyl group, R2represents a hydrogen atom, R4represents a hydroxy-group, and X represents a methylene group; R1represents a methyl group, R2represents a methyl group, R4represents a hydrogen atom, and X represents a methylene group; R1represents a hydrogen atom, R2represents a hydrogen atom, R4represents a hydroxy-group, and X represents a methylene group; or R1represents a methyl group, R2represents a methyl group, R4represents a hydroxy-group, and X represents a sulfur atom.

2. Connection on p. 1 or its pharmaceutically acceptable salt, where R1represents a methyl group, R2represents a methyl group, R4represents a hydroxy-group, and X represents metileno is the ne of the compounds of formula (Ia) or its pharmaceutically acceptable salt

where R1represents a hydrogen atom or methyl group;
R2arepresents a hydrogen atom, a protective group for a hydroxy-group or methyl group;
R3represents a hydrogen atom or a protective group for a hydroxy-group;
R4arepresents a hydrogen atom, a hydroxy-group or a protected hydroxy-group;
R5represents a hydrogen atom or a protective group for a hydroxy-group;
X represents a methylene group or a sulfur atom,
provided that when X represents a sulfur atom, R1represents a methyl group, R2arepresents a methyl group, and R4arepresents a hydroxy-group or a protected hydroxy-group; when X represents a methylene group, R1represents a methyl group, and R2arepresents a hydrogen atom, R4arepresents a hydroxy-group or a protected hydroxy-group; or when X represents a methylene group, and R1represents a hydrogen atom, R2arepresents a methyl group, and R4arepresents a hydroxy-group or a protected hydroxy-group;
and that if X represents a methylene group, R4acan't imagine a hydroxy-group, when R5represents a hydrogen atom, and R4aand R5not may together represent oxyalkylene group;
and that excludes the connection, where X represents a methylene group, R1represents a hydrogen atom, R2arepresents a methyl group, R3is pivaloyloxy group, R4ais acetoxy, and R5represents acetyl group.

4. The compound of formula (Ia) under item 3, where the protective group for the hydroxy-group is chosen from the group comprising groups such as tetrahydropyranyl, tetrahydropyranyl, silyl, aralkyl, Uralelectromed, 1-(aliphatic, acyloxy-(lower alkyl), 1-(cycloalkylcarbonyl)-(lower alkyl), (1 being the lowest, alkoxycarbonyl)-(lower alkyl), 1-(cycloalkylcarbonyl) -(lower alkyl), phthalidyl and oxadiazolidine.

5. The compound of formula (Ia) under item 3, where the protective group for the hydroxy-group is chosen from the group comprising groups such as tetrahydropyran-2-yl, 4-methoxyacridine-4-yl, tetrahydrothiopyran-2-yl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, di(tert-butyl)methylsilyl, diphenylmethylsilane, benzyl, diphenylene, 4 methoxybenzyloxy-carbonyl, 2-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl, acetoxymethyl, propionylacetate, butyraldoxime, pivaloyloxymethyl, valerolactone, 1-acetoxyethyl, butyrylacetate, 1-pivaloyloxymethyl, cyclopentanecarboxylate, cyclohexylcarbodiimide, 1-cyclopentanecarboxylate, 1-cyclohexylcarbodiimide, methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonyl, isopropoxycarbonyloxymethyl, butoxycarbonylmethyl, msobuttoniconandcaption, 1-(methoxycarbonylamino)ethyl, 1-(ethoxycarbonyl)ethyl, 1-(isopropoxycarbonyl)ethyl, cyclopentanecarboxylate, cyclohexyloxycarbonyloxy, 1-(cyclopentanecarbonyl)ethyl, 1-(cyclohexyloxycarbonyloxy)ethyl, phthalidyl, (5-phenyl-2-oxo-1,3-dioxolan-4-yl)methyl, [5-(4-were)-2-oxo-1,3-dioxolan-4-yl] methyl, (5-methyl-2-oxo-1,3-dioxolan-4-yl)methyl and (5-ethyl-2-oxo-1,3-dioxolan-4-yl)methyl.

6. The compound of formula (1A) under item 3, where the protective group for the hydroxy-group is chosen from the group comprising groups such as trimethylsilyl, tert-butyldimethylsilyl, triphenylmethyl, benzyl, 4-methoxybenzyl, acetoxymethyl, propionylacetate, butyraldoxime, pivaloyloxymethyl, ethoxycarbonylmethyl, propoxycarbonyl, isopropoxycarbonyloxymethyl, butoxycarbonylmethyl, msobuttoniconandcaption, cyclopentanecarboxylate, cyclohexyloxycarbonyloxy, (5-phenyl-2-oxo-1,3-dioxolan-4-yl)methyl, [5-(4-were)-2-oxo-1,3-dioxolan-4-yl] methyl, (5-methyl-2-oxo-1,3-dioxolan-4-yl)methyl and (5-ethyl-2-oxo-1,3-dioxolan-4-yl)methyl.

7. Ester derivative of compound (1A) according to any one of paragraphs.3-6, where the ester residue is a group R6CO - or R6OCO-, where R6selected from the group consisting of hydrogen, C1-C21alkyl groups; C2-C21alkenylphenol or alkenylphenol group having from 1 to 3 double or triple links; C1-C21alkyl groups, substituted by 1-4 substituents selected from the group comprising group, lower alkoxy, halogen and nitro; C1-C21alkyl groups, substituted 1-3 C6-C10aryl groups that are optionally substituted by 1-4 substituents selected from the group consisting of the groups lower alkyl, lower alkoxy, halogen and nitro; and (C6-C10aryl group which is optionally substituted by 1-4 substituents selected from the group consisting of groups of the lower and oneevery the balance represents the group R6CO - or R6OCO-, where R6selected from the group consisting of hydrogen, C1-C21alkyl groups; C2-C21alkenylphenol group having from 1 to 3 double bonds, With2-C6alkenylphenol group having one triple bond; C1-C6alkyl groups, substituted by 1-4 substituents selected from the group comprising group C1-C4alkoxy, halogen and nitro; C1-C6alkyl groups, substituted 1-3 C6-C10aryl groups that are optionally substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro; and (C6-C10aryl group, which optionally is substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro.

9. Ester derivative of compound (Ia) according to any one of paragraphs.3-6, where the ester residue is a group R6CO - or R6OCO-, where R6selected from the group consisting of C1-C21alkyl groups; C6-C20alkenylphenol group having from 1 to 3 double bonds, With2-C6alkenylphenol group having one triple bond; C14alkoxy and nitro; C1-C6alkyl group substituted by 1-3 substituents selected from the group consisting of halogen; C1-C4alkyl group substituted by 1-3 phenyl or raftiline groups, which are optionally substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro; and phenyl or naftilos group, which optionally is substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro.

10. Ester derivative of compound (Ia) according to any one of paragraphs.3-6, where the ester residue is a group R6CO - or R6OCO-, where R6selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds; C3-C5alkenylphenol group having one triple bond; C1-C4alkyl groups substituted by one Deputy, selected from the group consisting of groups C1-C4alkoxy and nitro; C1-C4alkyl group substituted by 1-3 substituents selected from the group consisting of the groups fluorine and chlorine; C1-C4al is nami from the group consisting of groups C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine; and the phenyl group, which optionally is substituted by 1-3 substituents selected from the group consisting of groups C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine.

11. Ester derivative of compound (Ia) according to any one of paragraphs.3-6, where the ester residue is a group R6CO - or R6OCO-, where R6selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds; C3-C5alkenylphenol group having one triple bond; C1-C4alkyl groups substituted by one Deputy, selected from the group consisting of groups C1-C4alkoxy, fluorine, chlorine and nitro; C1-C4alkyl group substituted by 1-3 phenyl groups which are optionally substituted by 1 or 2 substituents selected from the group consisting of groups C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine; and the phenyl group, which optionally is substituted by 1-3 substituents selected from the group consisting of groups C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine.

12. Ester derived soybean is 6 selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds; C3-C5alkenylphenol group having one triple bond; C1-C4alkyl groups substituted by one Deputy, selected from the group consisting of groups C1-C4alkoxy; and C1-C4alkyl group substituted by 1 or 2 phenyl groups optionally substituted by 1 or 2 substituents selected from the group consisting of groups C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine.

13. Ester derivative of compound (Ia) according to any one of paragraphs.3-6, where the ester residue is a group R6CO - or R6OCO-, where R6selected from the group including C6-C20alkyl group, and C10-C20alkenylphenol group having from 1 to 3 double bonds.

14. Simple ether derivative of compound (Ia) according to any one of paragraphs.3-6, where a simple essential residue selected from the group consisting of C1-C21alkyl groups; C2-C21alkenylphenol or alkenylphenol group having from 1 to 3 double or triple links; C1-C21alkyl groups containing 1-4 substituent selected and6-C10aryl groups that are optionally substituted by 1-4 substituents selected from the group comprising groups such as lower alkyl, lower alkoxy, halogen and nitro; and (C6-C10aryl group which is optionally substituted by 1-4 substituents selected from the group comprising groups such as lower alkyl, lower alkoxy, halogen and nitro.

15. Simple ether derivative of compound (Ia) according to any one of paragraphs.3-6, where a simple essential residue selected from the group consisting of C1-C21alkyl groups; C2-C21alkenylphenol group having from 1 to 3 double bonds, C2-C6alkenylphenol group having one triple bond; C1-C6alkyl groups containing 1-4 substituent selected from the group comprising group C1-C4alkoxy, halogen and nitro; C1-C6alkyl groups containing 1-3 C6-C10aryl group, which optionally is substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro; and (C6-C10aryl group, which optionally is substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1E is a simple essential residue selected from the group consisting of C1-C21alkyl groups; C6-C20alkenylphenol group having from 1 to 3 double bonds, C2-C6alkenylphenol group having one triple bond; C1-C6alkyl group which has one Deputy, selected from the group comprising group C1-C4alkoxy and nitro; C1-C6alkyl group that contains 1-3 substituent selected from the group consisting of the groups halogen; C1-C4alkyl groups having from 1 to 3 phenyl or naftalina groups, which are optionally substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro; and phenyl or naftilos group, which optionally is substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro.

17. Simple ether derivative of compound (Ia) according to any one of paragraphs.3-6, where a simple essential residue selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds, C3-C5alkenylphenol group having one triple bond; C1-C4alkyl is nitro; C1-C4alkyl group which has 1-3 substituent selected from the group consisting of the groups fluorine and chlorine; C1-C4alkyl groups having from 1 to 3 phenyl groups which are optionally substituted by 1 or 2 substituents selected from the group comprising group C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine; and the phenyl group, which optionally is substituted by 1-3 substituents selected from the group comprising group C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine.

18. Simple ether derivative of compound (Ia) according to any one of paragraphs.3-6, where a simple essential residue selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds, C3-C5alkenylphenol group having one triple bond; C1-C4alkyl group which has one Deputy, selected from the group comprising group C1-C4alkoxy, fluorine, chlorine and nitro; C1-C4alkyl groups having from 1 to 3 phenyl groups which are optionally substituted by 1 or 2 substituents selected from the group comprising group C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine; and vanilin the2alkyl, C1-C4alkoxy, fluorine and chlorine.

19. Simple ether derivative of compound (Ia) according to any one of paragraphs.3-6, where a simple essential residue selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds, C3-C5alkenylphenol group having one triple bond; C1-C4alkyl group which has one Deputy, selected from the group comprising C1-C4alkoxy group; and (C1-C4alkyl group which has 1 or 2 phenyl groups, optionally substituted by 1-2 substituents selected from the group comprising group C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine.

20. Simple ether derivative of compound (Ia) according to any one of paragraphs.3-6, where a simple essential residue selected from the group consisting of C6-C20alkyl groups and C10-C20alkenylphenol group having from 1 to 3 double bonds.

21. N-allylcarbamate derivative of compound (Ia) according to any one of paragraphs. 3-6, where the alkyl residue selected from the group consisting of C1-C21alkyl groups; C2-C21alkenylphenol or alkenylphenol group having from 1 to 3 double or triple withlower alkoxy, halogen and nitro; and (C1-C21alkyl group which has 1-3 C6-C10aryl group, optionally substituted by 1-4 substituents selected from the group including the group of lower alkyl, lower alkoxy, halogen and nitro.

22. N-allylcarbamate derivative of compound (Ia) according to any one of paragraphs. 3-6, where the alkyl residue selected from the group consisting of C1-C21alkyl groups; C2-C21alkenylphenol group having from 1 to 3 double bonds; C2-C6alkenylphenol group having one triple bond; C1-C6alkyl group which has from 1 to 4 substituents selected from the group comprising group C1-C4alkoxy, halogen and nitro; and (C1-C6alkyl group which has 1-3 C6-C10aryl group, optionally substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro.

23. N-allylcarbamate derivative of compound (Ia) according to any one of paragraphs. 3-6, where the alkyl residue selected from the group consisting of C1-C21alkyl groups; C6-C20alkenylphenol group having from 1 to 3 double bonds; C2-C6alkenylphenol group,group, including group C1-C4alkoxy and nitro; and (C1-C6alkyl group which has from 1 to 3 substituents selected from the group comprising group halogen; and (C1-C4alkyl group which has 1 to 3 phenyl or naftalina groups, which are optionally substituted by 1-3 substituents selected from the group comprising group C1-C4alkyl, C1-C4alkoxy, halogen and nitro.

24. N-allylcarbamate derivative of compound (Ia) according to any one of paragraphs. 3-6, where the alkyl residue selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds; C3-C5alkenylphenol group having one triple bond; C1-C4alkyl group which has one Deputy, selected from the group comprising group C1-C4alkoxy and nitro; C1-C4alkyl group which has from 1 to 3 substituents selected from the group including the group of fluorine and chlorine; and (C1-C4alkyl group which has 1 to 3 phenyl groups which are optionally substituted by 1-2 substituents selected from the group comprising groups such as C1-C2alkyl, C1-C4 is hydrated residue selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds; C3-C5alkenylphenol group having one triple bond; C1-C4alkyl group which has one Deputy, selected from the group comprising group C1-C4alkoxy, fluorine, chlorine and nitro; and (C1-C4alkyl group which has 1 to 3 phenyl groups which are optionally substituted by 1-2 substituents selected from the group comprising groups such as C1-C2alkyl, C1-C4alkoxy, fluorine and chlorine.

26. N-allylcarbamate derivative of compound (Ia) according to any one of paragraphs. 3-6, where the alkyl residue selected from the group consisting of C6-C20alkyl groups; C10-C20alkenylphenol group having from 1 to 3 double bonds; C3-C5alkenylphenol group having one triple bond; C1-C4alkyl group which has one Deputy, selected from the group comprising group C1-C4alkoxy; and C1-C4alkyl group which has from 1 to 2 phenyl groups which are optionally substituted by 1-2 substituents selected from the group comprising groups such as C1-C26-C20alkyl groups and C10-C20alkenylphenol group having from 1 to 3 double bonds.

28. The compound of formula (Ib) selected from the group of compounds consisting of the following compounds, or pharmaceutically acceptable salt:

connection, where R1represents a methyl group, R2represents a methyl group, R3arepresents a hydrogen atom, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a hydrogen atom, R3arepresents a hydrogen atom, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3arepresents a hydrogen atom, R4arepresents a hydrogen atom, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1is METI isarepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3ais eurolog group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3ais meritorious group, R4arepresents a hydroxy-group, R4arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3ais pentadecanolide group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3ais Palmitoyl group, R4arepresents a hydroxy-group, R5arepresents the atom sup> represents a hydrogen atom, R3arepresents a hydrogen atom, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a hydrogen atom, R2represents a methyl group, R3ais technology group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a hydrogen atom, R2represents a methyl group, R3ais eurolog group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a hydrogen atom, R2represents a methyl group, R3ais meritorious group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a hydrogen atom, R2represents a methyl group, R3ais pentadecanolide group, R4a connection, where R1represents a hydrogen atom, R2represents a methyl group, R3ais Palmitoyl group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a hydrogen atom, R2represents a methyl group, R3arepresents a hydrogen atom, R4arepresents a hydroxy-group, R5ais Palmitoyl group, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3ais octyloxyphenyl group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group;
connection, where R1represents a methyl group, R2represents a methyl group, R3ais nonlexically group, R4arepresents a hydroxy-group, R5arepresents a hydrogen atom, and X represents a methylene group; and
connection, where R1represents a methyl group, R25arepresents a hydrogen atom, and X represents a methylene group.

29. The compound of formula (Ik) selected from the group of compounds consisting of the following compounds, or pharmaceutically acceptable salt:

connection, where R1represents a methyl group, R11represents a methyl group, R3represents a hydrogen atom, and R5represents a hydrogen atom; and
connection, where R1represents a methyl group, R11is dodecyloxy group, R3represents a hydrogen atom, and R5represents a hydrogen atom.

30. Pharmaceutical composition having antibacterial activity comprising an effective amount of antibacterial active compound together with a carrier or diluent, where the aforementioned antibacterial active compound is a compound according to any one of paragraphs.1-29 or its pharmaceutically acceptable salt.

31. The compound according to any one of paragraphs.1-29 or its pharmaceutically acceptable salt having antibacterial activity.

32. Agent containing the compound according to any one of paragraphs.1-29 or its pharmaceutically acceptable salt with an antibacterial act is TBE antibacterial agent.

34. Method for the treatment or prevention of diseases which are amenable to treatment or prevention with the help of which have antibacterial activity of compounds, which includes the introduction in need of such treatment to the mammal an effective amount of a compound according to any one of paragraphs.1-29 or its pharmaceutically acceptable salt.

35. The strain Streptomyces griseus SANK 60196 (FERM BP-5420), capable of producing compounds according to any one of paragraphs.1, 2, 36, 37, 39 or 40.

36. Connection A-E formula (XI) or its salt

37. Compound a IS a 500359F formula (XII) or its salt

38. Amide derivative of compound A-500359F formula (XIIl) or its salt

39. Connection A-N formula (XIV) or its salt

40. Compound a IS a 500359J formula (XV) or its salt

41. Connection A-M-3 formula (XVI) or its salt

42. The way to obtain compound A-500359E, A-500359F AND N, A-500359J according to any one of paragraphs.36, 37, 39 or 40, characterized in that exercise i)the cultivation of the producer strain Streptomyces griseus; (ii)isolation of compounds from food cultivation and cleaning; and (iii)optional, p is.

44. Pharmaceutical composition having antibacterial activity comprising an effective amount of antibacterial active compound together with a carrier or diluent, where the aforementioned antibacterial active compound is a compound according to any one of paragraphs.36-41 or its pharmaceutically acceptable salt.

45. The compound according to any one of paragraphs.36-41 or its pharmaceutically acceptable salt having antibacterial activity.

46. The compound according to any one of paragraphs.36-41 or its pharmaceutically acceptable salt for use as an antibacterial agent.

47. Agent containing the compound according to any one of paragraphs.36-41 or its pharmaceutically acceptable salt having antibacterial activity.

48. Method for the treatment or prevention of diseases which are amenable to treatment or prevention with the help of which have antibacterial activity of compounds, which includes an introduction to a mammal in need of such treatment, an effective amount of a compound according to any one of paragraphs.36-41 or its pharmaceutically acceptable salt.

Priority items:
09.07.1998 on PP. 1, 2 and 35;
24.09.1998 on PP. 36 and 39;
09.07.1999 on all other points.

 

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whererepresents a single or double bond; R1represents a C1-C4alkyl; R2represents a C1-C4alkyl or C3-C6cycloalkyl; R1and R2together with the carbon atom to which they are joined, can form WITH3-C6cycloalkyl, optionally substituted stands; And represents СООR3CHO, CH2OH, COCH2HE, CONHCH2CH2OH, CONHOH or

R3hydrogen, C1-C12alkyl, which can be broken od is alkoxy, halogen, hydroxyl, C3-C6cycloalkyl, benzyloxy, fullam, phenyl, furfuryl, galopera, lower alkylphenyl, lower alkoxyphenyl, nitrophenyl, carboxyla, lower alkoxycarbonyl, cyano, C1-C4alkylthio or three (lower) alkylammonium; C3-C6alkenyl, optionally substituted by one of the following groups:1-C3alkoxy, phenyl, halogen or two WITH1-C3alkoxygroup or two halogen groups; C3-C6cyclooctyl, optionally substituted by one or two1-C3alkyl groups; C3-C10quinil, optionally substituted by phenyl, halogen or CH2IT; or the cation of an alkali metal or alkaline-earth metal (CA, BA) manganese, copper, iron, ammonium, or organic ammonium; RWITHand RDrepresent N or CH3; Represents N; COR4or SO2R5provided that when a represents a COR4or SO2R5and is a СOOR3the radical R3cannot be hydrogen or a salt-forming cation; R4represents a C1-C11alkyl, chloromethyl or phenyl, optionally substituted A5 alkyl or phenyl, optionally substituted one metalno, chloro - or nitro-group; W represents 0 or S; X represents 0, S or whenis a single bond, the group S 0; Y and Y', Z and Z' represent hydrogen, halogen, C1-C6alkyl, C1-C4hydroxy (lower) alkyl, C1-C6alkoxy, C1-C6acyloxy, benzoyloxy, optionally substituted by one or two1-C4alkyl, C1-C4alkoxygroup or halogen; C1-C4alkylthio, phenoxy,1-C4haloalkyl,1-C4haloalkoxy, nitro, cyano, C1-C4alkylamino,1-C4dialkylamino,1-C4alkylsulfonyl or phenyl, optionally substituted by one or more1-C4the alkyl, C1-C4alkoxy, halogen, or any combination of these two groups, where Y and Z are the same provided that Y and Z represent hydrogen, halogen, alkyl or alkoxy, and when Y and Y' or Z and Z' are the same group they are hydrogen or alkyl; and taken together, Y and Z form a ring in which YZ has the structural formula -(CH2)n- where n являе/www.fips.ru/fullimg/rupat2/19962/004.dwl/2058313-8t.gif" ALIGN="ABSMIDDLE">-=where L, M, Q, and R7each represent hydrogen, halogen, nitro, C1-C4lower alkyl, C1-C4lower alkoxy, methoxy, phenyl, phenoxy, provided that only one of the radicals L, M, Q or R7may have a value different from hydrogen, halogen, C1-C4the alkyl or C1-C4alkoxy; or a pyridine-N-oxides, when W represents oxygen or sulfur and a is COOR3; and when R1and R2not the same, the optical isomers of these compounds, except for the case when R3represents a salt-forming cation, their salts kislotoustoichivam

The invention relates to medicine, namely, venereology, and can be used for the treatment of chronic gonorrhoea

The invention relates to the field of medicine

The invention relates to the derivatives of cyclobutylamine formula (I), where Q is a quinolone derivative, and R1, R2, R3, R4and n are such as defined in the claims

,-disubstituted derivatives of 9-desoxo-9a-n-ethynyl-9a-aza - 9a-homoerythromycin and" target="_blank">

The invention relates to,-disubstituted derivatives of 9-desoxo-9a-N-ethynyl-9a-Aza-9a-homoerythromycin And the General formula (I), where R1and R2mutually the same or different and represent nitrile, carboxypropyl formula COOR3where R3is1-C4is an alkyl group, or ketogroup formula COR4where R4represents C1-C4is an alkyl group, and their pharmaceutically acceptable additive salts with inorganic or organic acids

The invention relates to the field of medicine and relates to pharmaceutical compositions with antibacterial activity
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