Cinnamic acid compounds (versions), intermediate compounds for their obtaining, based on them pharmaceutical composition, method of inhibiting histone diacetase, method of treating diabetes, method of treating tumour or disease associated with cell proliferation, method of enhancing axon growth and method of treating neurodegenerative diseases and spinal muscular atrophy

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, represented by the following formula (I) and their pharmaceutically acceptable salts, where values for groups R1, R4-R6, Ra, m, n, Y, X are determined in the invention formula. Said compounds are used as preparations for enhancing growth of axons and prevention of diseases associated with histone diacetases, in particular tumours or diseases associated with cell proliferation.

EFFECT: compounds in accordance with the claimed invention can be used as anti-cancer, antidiabetic agents and anti-neurodegenerative agents in case of diseases such as Alzheimer's disease, Huntington's disease, spinocerebral ataxia and spinal muscular atrophy in people.

18 cl, 44 dwg, 13 ex

 

The text descriptions are given in facsimile form.

1. Compounds cinnamic acid covered by the General structural formula (I)

where
R1represents hydrogen, C1-4alkyl or C2-6alkenyl,
X represents O or-CH2-,
Y represents O, NH or N-C1-4alkyl,
n represents the integer 0, 1, 2, 3, 4 and 5,
m is an integer 0, 1, 2, 3, 4 and 5,
Rarepresents H or C1-10alkyl which may be substituted by hydroxy, C2-10alkenyl or a heterocycle which may be optionally substituted by at least one1-4the alkyl
R4represents H, C1-4alkyl, C5-6cycloalkyl or 5 - or 6-membered unsaturated carbocycle or a heterocycle which may be substituted with halogen, CF3, CCl3, CBr3, OCF3C1-6the alkyl or or7where R7represents hydrogen or C1-6alkyl,
R5represents H, OH, OK, OLi, NH2C1-4alkyl or 6-membered unsaturated carbocycle or benzyl, where the alkyl, carbocycle optionally substituted NH2and benzyl optionally substituted with halogen, and
R6represents H or, together with R1represents a C2H2and their pharmaceutically acceptable salts,
provided that the excluded compounds cinnamic acid covered by the General structural formula (I), with the following set of substituents:
Y represents O, R5represents H, R1and R6form-C2H2-, X represents O, Rarepresents methyl, R4represents methyl, n and m are 0, Z-isomer,
Y represents O, R5represents H, R1and R6form-C2H2- , X represents O, Rarepresents H, R4represents methyl, n and m are 0, Z-isomer,
Y represents Oh, R5represents H, X represents-CH2-, R4represents methyl, n and m are 0, Rais a 1-isobutylene, R6represents H, R1represents methyl, Z-isomer,
Y represents Oh, R5represents H, X represents-CH2-, R4represents ethyl, n and m are 0, Rais a 1-isobutylene, R6represents H, R1represents methyl, Z-isomer,
Y represents O, R5represents H, X represents O, Rarepresents methyl, R4represents methyl, n and m are 0, R6represents H, R1represents methyl, Z-isomer,
Y represents O, R5represents H, X represents O, Rarepresents methyl, R represents methyl, n and m are 0, R6represents H, R1represents methyl, E-isomer,
Y represents O, R5represents H, X represents O, Ra, R4, R6and R1represent H, Z - and E-isomers,
Y represents O, R5represents methyl, X represents O, n and m are 0, Ra, R4and R1represent methyl, R6represents H, E-isomer,
Y represents O, R5represents methyl, X represents O, n and m are 0, Ra, R4and R1represent methyl, R6represents H, Z - and E-isomers,
Y represents O, R5represents methyl, X represents O, n and m are 0, Rarepresents H, R4and R1represent methyl, R6represents H, Z - and E-isomers,
Y represents O, R5represents methyl, X represents O, n and m are 0, R1and R6represent H, R4represents methyl, R6represents H, Z - and E-isomers,
Y represents O, R5represents H, X represents O, Rarepresents methyl, R4, R6and R1represent H, Z - and E-isomers,
Y represents O, R5represents H, X isone O, n and m are 0, Ra, R4and R1represent n-butyl, R6represents H, E-isomer,
Y represents O, R5represents H, X represents - CH2-, R4represents H, n and m are 0, Rais a 1-isobutylene, R6represents H, R1represents H, E-isomer,
Y represents O, R5represents H, n and m are 0, R4represents H, X represents O, R1and R6form-C2H2-, Rarepresents methyl, Z-isomer,
Y represents O, R5represents methyl, X represents-CH2-, n and m are 0, R6represents H, R4represents methyl, R1represents H, Rarepresents vinyl, E-isomer,
Y represents O, R5represents methyl, X represents-CH2-, n and m are 0, Rarepresents H, R4represents methyl, R1represents H, Rais a 1-isobutylene, E-isomer,
Y represents O, R5represents H, n and m are 0, R4represents H, X represents O, R1and R6form-C2H2-, R6represents methyl, E-isomer,
Y is NH, R5is the th H, n and m are 0, R6represents H, X represents O, R4represents methyl, R1and Rarepresent methyl, E-isomer,
Y is NH, R5represents H, n and m are 0, R6represents H, X represents O, R4represents methyl, R1and Rarepresent methyl, Z - and E-isomers,
Y represents O, R5represents ethyl, n and m are 0, R4represents H, X represents-CH2-, R6represents H, Rarepresents vinyl, R1represents methyl, E-isomer,
Y is NH, R5represents NH2n and m are 0, R1and R6form-C2H2-, R4represents H, Rarepresents methyl, X represents O, Z - and E-isomers,
Y is NH, R5represents H, n, and m is 0, X represents Oh, R4represents methyl, Rarepresents methyl, R1and R6form-C2H2-, Z - and E-isomers,
Y represents O, R5represents ethyl, n and m are 0, R4represents H, X represents-CH2-, R6represents H, R4represents H, Rarepresents vinyl, R1represents METI is, Z - and E-isomers,
Y represents O, R5represents H, n and m are 0, R4represents H, X represents O, R1and R6form-C2H2-, Rarepresents methyl, Z - and E-isomers,
Y represents O, R5represents ethyl, n and m is 0, X represents-CH2-, R1and R6form-C2H2-, Rarepresents H, R4represents methyl, E-isomer,
Y represents O, R5represents H, n and m are 0, R4represents H, X represents Oh, R1and R6form-C2H2-, Rarepresents H, Z - and E-isomers,
Y represents O, R5represents H, n and m are 0, R4represents methyl, R6represents H, X represents O, Rarepresents methyl, R1represents ethyl, Z - and E-isomers,
Y represents O, R5represents H, n and m are 0, R4represents methyl, R6represents H, X represents O, Rarepresents ethyl, R1represents methyl, Z+E isomers,
Y is O, X is O, R5represents ethyl, R1, R4, R6and Rarepresent H, E-isomer,
Y represents O, X depict the defaults a-CH 2-, R1and R4represent methyl, R5and R6represent H, Rais a 1-isobutylene, n and m are 0, E-isomer,
Y represents O, X represents-CH2-, R1, Raand R6represent H, R4represents a 1,3-dichlorophenyl, R5represents ethyl, n is 0, m is 1, E-isomer,
Y represents O, X represents-CH2-, R1and R4represent methyl, R5, R6and Rarepresent H, n and m are 0, E-isomer,
Y represents O, X represents-CH2-, R1, R4and R6represent methyl, Rais a 1-isobutylene, R6represents H, n and m are 0, Z-isomer,
Y represents O, X represents-CH2-, R1represents methyl, R4and R5are ethyl, R6represents H, Rais a 1-isobutylene, n and m are 0, Z-isomer,
Y represents O, X represents-CH2-, R1represents methyl, R4, R5and R6represent H, Rarepresents a 1,2-epoxy-2-methylpropyl, n and m are 0, Z+E isomers,
Y represents O, X represents-CH2-, R1represents methyl, R4, R5, R6R arepresent H, n and m are 0, E-isomer,
Y is O, X is O, R1and R6form-C2H2-, R4and R5represent H, Rarepresents a 3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidyl, n is 4, n is 0, E-isomer,
Y is O, X is O, R1and R6form-C2H2-, R4represents H, R5represents ethyl, Rarepresents a 3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidyl, n is 4, m is 0, E-isomer,
Y is O, X is O, R4, R5and R6represent methyl, R1and R6form-C2H2-, n and m are 0, E-isomer,
Y is O, X is O, R4, R5and Rarepresent methyl, R1and R6form-C2H2-, n and m are 0, Z-isomer,
Y represents O, R4and R5represent H, R1and R6form-C2H2-, Rarepresents n-butyl, n and m are 0, Z-isomer.

2. Compounds according to claim 1, in which X represents-CH2-.

3. Compounds according to claim 1, in which n and m is 1.

4. Compounds according to claim 1, which is selected from the group including













































.

5. Connection max is th acid, covered by the General structural formula (II)

where R1represents hydrogen, C1-4alkyl or C2-6alkenyl,
X represents-CH2-O,
Y represents O, NH, or N-C1-4alkyl,
n represents the integer 0, 1, 2, 3, 4 and 5,
m is an integer 0, 1, 2, 3, 4 and 5,
R2and R3independently represent a1-6alkyl,
R4represents H, C1-4alkyl, C5-6cycloalkyl or 5 - or 6-membered unsaturated carbocycle or a heterocycle which may be substituted with halogen, CF3, CCl3, CBr3, OCF3C1-6the alkyl, OR7where R7represents hydrogen or C1-6alkyl,
R5represents H, OH, OK, OLi, NH2C1-4alkyl or 6-membered unsaturated carbocycle or benzyl, where the alkyl or carbocycle optionally substituted NH2and benzyl optionally substituted with halogen, and
R6represents H or, together with R1represents a C2H2-,
and their pharmaceutically acceptable salts, provided that the excluded compounds cinnamic acid covered by the General structural formula (I), with the following set of substituents:
Y represents O, X represents-CH2-, R5and R6represent H, R1, R2, R3and 4represent methyl, n and m are 0, Z-isomer,
Y represents O, X represents-CH2-, R6and R6represent H, R1, R2and R3represent methyl, R4represents ethyl, n and m are 0, Z-isomer,
Y represents O, X represents-CH2, R1, R4, R5and R6represent H, R2and R3represent methyl, n and m are 0, E-isomer,
Y represents O, X represents-CH2-, R1and R6represent H, R2, R3, R4and R5represent methyl, n and m are 0, E-isomer,
Y represents O, X represents-CH2-, R1, R2, R3and R4represent methyl, R5and R6represent H, n and m are 0, E-isomer,
Y represents O, X represents-CH2-, R2and R3represent methyl, R1, R4, R6and R6represent H, n and m are 0, Z-isomer,
Y represents O, X represents-CH2-, R1, R2, R3, R4and R5represent methyl, R6represents H, n and m are 0, Z-isomer,
Y represents O, X represents-CH2-, R1, R2and R3represent methyl, R4and R5is own the th ethyl, R6represents H, n and m are 0, Z-isomer.

6. Compounds according to claim 5, in which R1, R2and R3independently represents a C1-4alkyl, R4represents phenyl or phenyl substituted with halogen, CF3, CCL3, CBr3OS1-4the alkyl, R5represents phenyl or phenyl substituted NH2and R6represents hydrogen.

7. Compounds according to claim 5, in which R1, R2and R3independently represent methyl, R4represents phenyl or phenyl, substituted by F, Cl, Br, CF3, CCl3, CBF3, OCH3, R5represents OH or phenyl, substituted NH2and R6represents hydrogen.

8. Compounds according to claim 5, in which X represents-CH2-.

9. Compounds according to claim 5, in which n and m is 1.

10. Compounds according to claim 5, which is selected from the group including













































11. Pharmaceutical composition for inhibiting ristanovi deacetylase, comprising a therapeutically effective amount of a compound according to claim 1 or its pharmaceutically acceptable salt as an active substance and a pharmaceutically acceptable carrier.

12. A method of inhibiting ristanovi deacetylase, comprising introducing a therapeutically effectiveagainst compounds according to claim 1 or their pharmaceutically acceptable salts.

13. A method of treating diabetes, comprising introducing a therapeutically effective amount of the compounds according to claim 1 or their pharmaceutically acceptable salts.

14. A method of treating tumors or diseases associated with cell proliferation, including the introduction of therapeutically effective amounts of compounds according to claim 1 or their pharmaceutically acceptable salts.

15. A way to enhance axon growth, including the introduction of therapeutically effective amounts of compounds according to claim 1 or their pharmaceutically acceptable salts.

16. A method of treating neurodegenerative diseases and spinal muscular atrophy person, including the introduction of therapeutically effective amounts of compounds according to claim 1 or their pharmaceutically acceptable salts.

17. The method according to clause 16, in which the neurodegenerative disease is selected from the group including Huntington's disease and polyglutamine disease.

18. Intermediate compounds, which were used to obtain the compounds or pharmaceutically acceptable salts according to claim 1 or 5, selected from the group including



in which R is a p-H, p-Cl, p-Br or OCF3.



 

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SUBSTANCE: claimed invention relates to compounds of formula (I) or to their pharmaceutically acceptable salts, in which X is selected from group, consisting of-C(R1)2-, -O-, -S-, -S(O2)-, -NR1-; each R1 is independently selected from group consisting of H and alkyl; each of R2, R3 and R4 is independently selected from group consisting of (1) H, (2) alkyl, (3) -OR5, (4) alkylene-OR5, (5) -alkylene-R6, (6) -C(O)O-alkyl, (7) - alkylene-C(O)O-alkyl, (8) -alkylene-R8, (9) -NHR5, (10) -N(R5)2, (11) alkenyl, (12) -NH-R8, (13) -NH-CH(C(O)O(C1-C6)alkyl)-alkylene-O-alkyleneR6, (14)-NHCH(C(O)O(C1-C6)aalkyl)-alkylene-OH, (15) -NH-C(O)-alkenyl and (16) -N(C1-C6alkyl)C(O)-alkenyl; or R2 and R3 or R2 and R4 or R3 and R4 together with atoms with which they are bound, form condensed 3-7-member cycloalkyl or heterocycloalkyl ring, which represents non-aromatic monocyclic ring system, which contains in ring from about 5 to about 7 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen or oxygen, and said condensed cycloalkyl or heterocycloalkyl ring is not substituted or is substituted with one or several groups L3 ; and on condition that if X represents -O-, and m equals 1, then, at least, one of R2, R3 or R4 is not H; each R5 is independently selected from group consisting of (1) H, (2) (C1-C6)alkyl, (3) hydroxy-substituted alkyl, (4) R6, (5) R7, (6) -C(O)-(C1-C6)alkyl, (7) -C(O)-(C1-C6)halogenalkyl, (8) -C(O)-R6, (9) -C(O)-R7, (10) -C(O)NH-(C1-C6)alkyl, (11) -C(O)N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (12) -S(O)2-(C1-C6)alkyl, (13) -S(O)2-(C1-C6)halogenalkyl, (14) -S(O)2-R6, (15) -S(O)2-R7, (16) -S(O)2-R8, (17) -alkylene-C(O)-(C1-C6)alkyl, (18) -alkylene-C(O)-(C1-C6)halogen-alkyl, (19) -alkylene-C(O)-R6, (20) -alkylene-C(O)-R7, (21) -alkylene-S(O)2-(C1-C6)alkyl, (22) -alkylene-S(O)2-(C1-C6)halogenalkyl, (23) -alkylene-S(O)2-R6, (24) -alkylene-S(O)2-R7, (25) -alkylene-S(O)2-R8, (26) -alkylene-NHC(O)-(C1-C6)alkyl, (27) -alkylene-NHC(O)-(C1-C6)halogenalkyl, (28) alkylene-NHC(O)-R6, (29) -alkylene-NHC(O)-R7, (30) -alkylene-NHS(O)2-(C1-C6)alkyl, (31) -alkylene-NHS(O)2-(C1-C6)halogenalkyl, (32) -alkylene-NHS(O)2-R6, (33) -alkylene-NHS(O)2-R7, (34) -alkylene-N(alkyl)C(O)-(C1-C6)alkyl, (35) -alkylene-N(alkyl)C(O)-(C1-C6)halogenalkyl, (36) -alkylene-N(alkyl)C(O)-R6, (37) -alkylene-N(alkyl)C(O)-R7, (38) -alkylene-N(alkyl)S(O)2-(C1-Ce)alkyl, (39) -alkylene-N(alkyl)S(O)2-(C1-C6)halogen-alkyl, (40)-alkylene-N(alkyl)S(O)2-R6, (41) -alkylene-N(alkyl)S(O)2-R7, (42) -alkylene-C(O)-NH-(C1-C6)alkyl, (43) -alkylene-C(O)-NHR6, (44) -alkylene-C(O)-NHR7, (45) -alkylene-S(O)2NH-(C1-C6)alkyl, (46) -alkylene-S(O)2NH-R6, (47) -alkylene-S(O)2NH-R7 , (48) -alkylene-C(O)-N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (49) -alkylene-C(O)-N(alkyl)-R6, (50) -alkylene-C(O)-N(alkylene)-R7, (51) -alkylene-S(O)2N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (52) -alkylene-S(O)2N(alkyl)-R6, (53) -alkylene-S(O)2N(alkyl)-R7, (54) -alkylene-OH, (55) -alkylene-OC(O)-NH-alkyl, (56) -alkylene-OC(O)NH-R8, (57) -alkylene-CN, (58) -R8, (59) -alkylene-SH, (60) -alkylene-S(O)2-NH-R8, (61) -alkylene-S(O)2-alkylene-R6, (62) substituted with halogen alkylene, (63) -C(O)OR8, (64) -C(O)O(C1-C6)alkyl, (65) -C(O)R8, (66) -C(O)-alkylene-O-(C1-C6)alkyl, (67) -C(O)NH2, (68) -alkylene-O-(C1-C6)alkyl, (69) -alkylene-R8, (70) -S(O)2-halogen(C1-C6)alkyl, (71) hydroxy-substituted halogen(C1-C6)alkyl, (72) -alkylene-NH2, (73) -alkylene-NH-S(O)2-R8, (74) -alkylene-NH-C(O)-R8, (75) -alkylene-NH-C(O)O-(C1-C6)alkyl, (76) -alkylene-O-C(O)-(C1-C6)alkyl, (77) -alkylene-O-S(O)2-(C1-C6)alkyl, (78) -alkylene-R6 , (79) -alkylene-R7, (80) -alkylene-NH-C(O)NH-(C1-C6)alkyl, (81) -alkylene-N(S(O)2 halogen(C1-C6)alkyl)2, and each -S(O)2 halogen(C1-C6)alkyl fragment is selected independently, (82) -alkylene-N((C1-C6)alkyl)S(O)2-R8 , (83) -alkylene-OC(O)-N(alkyl)2, and each alkyl is selected independently, (84) -alkylene-NH-(C1-C6)alkyl, (85) -C(O)-alkylene-C(O)O-(C1-C6)alkyl, (86) -C(O)-C(O)-O-(C1-C6)alkyl, (87) -C(O)-alkylene-R6, (88) -C(O)-NH-R8, (89) -C(O)-NH-R6, (90) -C(O)-NH-alkylene-R6, (91) -C(O)-alkylene-NH-S(O)2-halogen(C1-C6)alkyl, (92) -C(O)-alkylene-NH-C(O)-O-(C1-C6)alkyl, (93) -C(O)-alkylene-NH2, (94) -C(O)-alkylene-NH-S(O)2-R8, (95) -C(O)-alkylene-NH-S(O)2-(C1-C6)alkyl, (96) -C(O)-alkylene-NH-C(O)-(C1-C6)alkyl, (97) -C(O)-alkylene-N(S(O)2(C1-C6)alkyl)2, and each -S(O)2(C1-C6)alkyl fragment is elected independently, (98) -C(O)-alkylene-NH-C(O)-NH-(C1-C6)alkyl, (99) -alkylene-O-R6, (100) -alkylene-R7, (101) -C(O)OH, (102) -alkylene-N(S(O)2(C1-C6)alkyl)2, (103) -alkylene-C(O)-O-(C1-C6)alkyl, (104) halogenalkyl, (105) halogen, (106) -alkylene-C(O)-NH2, (107) =N-O-(C1-C6)alkyl, (108) =N-O-alkylene-R6, (109) =N-O-alkenyl, (110) -N-O-R6, (111) =N-NH-S(O)2-R6, (112) alkenyl, (113) =R8, (114) -O-C(O)-R9, (115) -O-C(O)-(C1-C6)alkyl, (116)-CN, R6 is selected from group consisting of unsubstituted (C6-C14)aryl, (C6-C14)aryl, substituted with one or several groups L1, unsubstituted (C5-C14)heteroaryl and (C5-C14)heteroaryl, which represents aromatic monocyclic or bicyclic system, which contains in ring from about 5 to about 9 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen or sulphur, one or in combination, substituted with one or several groups L1; R7 is selected from group consisting of unsubstituted heterocycloalkyl and heterocycloalkyl which represents non-aromatic monocyclic system, which contains in ring from about 4 to about 6 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen substituted with one or several groups L2; R8 is selected from group consisting of unsubstituted cycloalkyl and cycloalkyl substituted with one or several groups L2; A8 is selected from group consisting of (a) unsubstituted aryl, (b) aryl substituted with one or several groups L1; each group L1 is independently selected fron group consisting of halogen, alkyl, -CN, -CF3, -O-(C1-C6)alkyl, -O-(halogen(C1-C6)alkyl), -alkylen-OH (-CH2OH); each group L2 is independently selected from group consisting of (a) -OH, (b) alkyl, (c) alkyl substituted with one or several groups -OH and (d) piperidyl; each group L3 is independently selected from group consisting of -CN, =O, R5 , -OR5 ; =N-R5 and -N(R5)2; n equals 0, 1, 2 or 3; and m equals 0, 1 or 2; and on condition that in composition of substituent -OR5 fragment R5 and oxygen atom, which it is bound with, do not form group -O-O-; and on condition that in composition of substituents -OR5, =N-R5 and -NHR5 R5 are not -CH2OH, -CH2NH2, -CH2NH-alkyl, -CH2NH-aryl or -C(O)OH. Invention also relates to pharmaceutical composition, as well as to application of one or several compounds by one of ii. 1-125.

EFFECT: obtaining novel biologically active compounds possessing properties of γ-secretase inhibitor.

127 cl, 447 ex, 94 tbl

FIELD: agriculture.

SUBSTANCE: improvement of effectiveness of insecticidal preparation is achieved through the use in sublethal doses of a mixture of fluorinated usnic acid (FUA) of the formula and II obtained by the reaction of (+)-usnic acid with perfluoropropene as a synergist of such insecticides. The decline of the latent period of the disease and increased mortality rate of larvae of Colorado potato beetle is marked using FUA and entomopathogenic microorganisms of Beauveria bassiana, Metarhizium anisopliae and Bacillus thuringiensis. The mixed composition of FUA at a concentration of 0.03% with a suspension of conidia of the fungus Bauveria bassiana with a titer of 3×106 conidia/ml (in vitro) and 5×106 conidia/ml (in the field) has proved to be the best in all respects.

EFFECT: increased biological efficiency of insecticides based on entomopathogenic fungi and bacteria.

1 cl, 4 tbl,5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing an optically active chromene oxide compound of formula or formula where R5, R6, R7, R8, R9, R10 and A are as described in the claim, and the absolute configuration of carbon atoms, denoted by *, denotes (R) or (S), which includes asymmetric epoxidation of a chromene compound of formula or formula with an oxidant in a solvent using optically active titanium complexes of formula formula formula and formula where R1, R2, R3 and R4 are defined in the claim, as a catalyst for asymmetric oxidation of the optically active chromene compound with high enantioselectivity and high chemical output.

EFFECT: efficient method of producing an optically active chromene oxide compound, which is an important intermediate compound used to produce a benzopyran compound, which is effective in treating arrhythmia.

18 cl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing ethers of substituted 5,6-dicyanobenzofuran-2-carboxylic acids of general formula: , where a R=4-CH3C6H4; b R=4-CH3O-C6H4; c R=2-thienyl; R1=CH3, C2H5, which can be used as precursors for producing biologically active substances, fluorescent materials and for synthesis of phthalocyanines. The method involves production of ethers of substituted 5,6-dicyanobenzofuran-2-carboxylic acids based on reaction of 4-bromo-5-nitrophthalonitrile and sodium salts of 2,4-dioxobutanoic acid derivatives, where reaction of said reagents takes place at temperature 75…85°C and molar ratio 1:2, respectively, for 18-24 hours in a dimethyl formamide solution, and the reaction mass is then diluted with ten-fold excess water at temperature T=0…25°C. The resinous residue is extracted with methylene chloride, thoroughly washed with water and chromatographed on silica gel. The eluent (solvent) is evaporated and the precipitate is filtered and recrystallised from alcohol.

EFFECT: high efficiency of the method.

1 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: in acidified indanylamines of general formula (I) R1-R4 have values given in description, A represents CH2, CHOH, B represents CH2 and R5 represents aryl or heteroaryl group, possibly substituted with substituents, listed in description. Said compounds are useful in regulation of endothelial nitrogen oxide synthase (eNOS) and, therefore they can be useful for production of medications for treatment of stable and unstable angina pectoris, Prinzmetal's angina, acute coronary syndrome, impaired heart function, cardiac infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, hypertension, lung hypertension, symptomatic hypertension, renovascular hypertension, erectile dysfunction, diabetes or diabetes complications, nephropathy, retinopathy, limited memory function, limited learning ability.

EFFECT: increase of composition efficiency.

37 cl, 441 ex, 2 tbl

The invention relates to compounds of General formula I

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

,

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

The invention relates to carboxylic acid derivative with condensed rings of the General formula (A), and its pharmaceutically acceptable salts, intending to obtain drugs that are effective agonists of the retinoic acid receptors

The invention relates to new derivatives of 4-hydroxypiperidine formula I

< / BR>
where X represents-O-, -NH-, -CH2-, -CH=, -SNON - or-CO-; R1-R4independently from each other denote hydrogen, a hydroxy-group, (lower) alkylsulfonyl or acetaminoph; R5-R8independently from each other denote hydrogen, a hydroxy-group, (lower)alkyl, halogen, (lower)alkoxygroup, trifluoromethyl or cryptometrics; a and b may denote a double bond, provided that when a represents a double bond, b is unable to designate a double bond; n = 0-2; m = 1-3; p = 0 or 1, and their pharmaceutically acceptable additive salts

The invention relates to aromatic amedieval derivatives and their salts, which have the ability to strong antikoaguliruyuschee action through reversible inhibition of activated coagulation factor, factor X (hereinafter referred to "FXA"), and which can be administered orally

The invention relates to a method for producing derivatives of 3-(5-methylfur-2-yl)-benzofuran having an antihypertensive, antianginal and antiarrhythmic activities

The invention relates to new derivatives of benzofuran-2-ones of formula 1, where a value of substituents specified in paragraph (1 formulas that can be used as stabilizers for organic polymers susceptible to oxidative, thermal or induced light decay

The invention relates to vasoconstrictor /(benzodioxan, benzofuran and benzopyran)-alkylamino/-alkyl-substituted guanidine formula I, their pharmaceutically acceptable salts, or their stereochemical isomers, where X = O, CH2or a direct bond; R1= H, C1-C4alkyl, R2= H, C1-C6alkyl, C3-C6alkenyl, C3-C6quinil, R3= H, C1-C4alkyl; or R2and R1taken together, may form a bivalent radical of the formula/CH2/m-, where m = 4 or 5; or R1and R2taken together may form a bivalent radical of formula-CH=CH -, or the formula/CH2/n-, where n = 2, 3 or 4; or R3may indicate a relationship when R1and R2taken together form a bivalent radical of formula-CH=CH-CH= -, -CH= CH-N= or-CH=N-CH=; where one or two hydrogen atom substituted by a halogen atom, a C1-C6alkoxygroup, C1-C6the alkyl, CN, NH, mono - or di(C1-C6alkyl) amino group, aminocarbonyl, C1-C6alkylaminocarbonyl, R4-H or C1-C6-alkyl; Alk1denotes a divalent C1-C3-ascandilwy radical, A denotes dwuhvalentny a radical of the formula /, lk2represents C2-C15-alcander or C5-C7-cycloalkenyl, and each "R" represents 0, 1, 2, R7and R8each independently is H, a halogen atom, a C1-C6by alkyl, hydroxyl, C1-C6allyloxycarbonyl, C1-C6alkoxygroup, cyano, amino, C1-C6the alkyl, carboxyla, nitro or amino group, aminocarbonyl, C1-C6alkylcarboxylic or mono - or di-(C1-C6)alkylamino, provided that excluded /2-/ (2,3-dihydro-1,4-benzodioxin-2-yl)-methyl/-amino/-ethyl-guanidine

The invention relates to new derivatives of N-(3-hydroxy-4-piperidinyl) (dihydro-2H-benzopyran or dihydrobenzoic) carboxamide, having valuable pharmaceutical properties, namely activity to stimulate gastrointestinal peristalsis

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to application of ester compounds of benzoic acid, taken from group, which includes 1-phenylvinyl 4-methoxybenzoate; 1-(4-methoxyphenyl)-vinyl 4-tert-butyl benzoate, 1-(4-tert-butylphenyl)-vinyl 4-methoxybenzoate, 1-phenylvinyl 4-tert-butyl benzoate, 4-benzoyloxy-2-methoxybenzolsulphonic acid, 3-diethylaminophenyl benzoate and 3-(1-pyrrolidinyl) phenyl benzoate and 3-methoxy salicylate, as component for preparing composition for protection of human organism or animal or material from ultraviolet radiation, containing effective quantity at least one of claimed compounds, as component for preparing composition, which is characterised by progressive protection from UV radiation, depending on duration of sun influence and level of sun radiation, as component for preparing composition for individual hygiene, which is characterised by progressive protection from UV radiation, depending on duration of sun influence and level of sun radiation, as component for preparing industrial composition, which is characterised by progressive protection from UV radiation, depending on duration of sun influence and level of sun radiation, and as component for preparing composition, which at photo-regrouping shows quantity of obtained UV-B radiation.

EFFECT: invention also relates to composition for protecting human or animal organism or protection of material from ultraviolet radiation, contains effective quantity of at least one above mentioned ester compound of benzoic acid.

40 cl, 6 dwg, 33 ex

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