Compounds representing styrene derivatives for treating ophthalmic diseases and disorders


FIELD: medicine, pharmaceutics.

SUBSTANCE: device refers to new styrene derivatives with the structure formula A in the form of geometrical isomers or tautomers and their pharmaceutical acceptable salts. In structural formula (A) R1 represents hydrogen; R2 represents hydrogen or C1-C6alkyl; R3, R4, R5 and R6 are identical or different and independently represent hydrogen, halogen, C1-C6alkyl or -OR12; R7 represents hydrogen or C1-C6alkyl; R8 represents hydrogen; R9 represents hydrogen, C1-C6alkyl, or -C(=O)R13; R10 represents hydrogen or C1-C6alkyl; Z represents W-Y, wherein W represents -C(R14)(R15)-; Y represents -C(R16)(R17)-; each R12 independently represents hydrogen or C1-C6alkyl; each R13 independently represents C1-C6alkyl; R14 and R15 are identical or different, and independently specified in hydrogen, fluoro, methyl, ethyl, trifluoromethyl, -OH, -OCH3 or -NH2; or R14 and R15 together form oxo; R16 and R17 are identical or different and independently represent hydrogen, halogen, C1-C6alkyl or -OR12. The other radical values are specified in the patent claim.

EFFECT: compounds may be used for treating an ophthalmic disease or disorder in an individual which can represent age-related macular degeneration or Stargardt macular degeneration.

17 cl, 14 tbl, 143 ex

 

The text descriptions are given in facsimile form.

1. The compound having the structure of formula (A):
,
in isolated E or Z geometric isomer or a mixture of E - and Z-geometric isomers, in the form of tautomer or a mixture of tautomers, in the form of a stereoisomer or pharmaceutically acceptable salt, where
R1represents hydrogen;
R2represents hydrogen or C1-C6alkyl;
R3, R4, R5and R6are the same or different and independently represent hydrogen, halogen, C1-C6alkyl or-OR12;
R7represents hydrogen or C1-C6alkyl;
R8represents hydrogen;
R9represents hydrogen, C1-C6alkyl, or-C(=O)R13;
R10represents hydrogen or C1-C6alkyl;
Z is a W-Y, where
W represents-C(R14)(R15)-;
Y represents-C(R16)(R17)-;
each R12independently represents hydrogen or C1-C6 alkyl;
each R13independently represents a C1-C6alkyl;
R14and R15are the same or different and independently selected from hydrogen, fluorescent, methyl, ethyl, trifloromethyl, -OH, -OCH3or-NH2; or R14and R15together form oxo;
R16and R17are the same or different and independently represent hydrogen, halogen, C1-C6alkyl or-OR12; or R16and R17together form oxo; or
may, R14and R16together form a direct bond, thus forming a double bond connecting W and Y; or perhaps, R14and R16together form a direct bond, and R15and R17together form a direct bond, thus forming a triple bond connecting W and Y; and
R11chosen from:
a) C1-C6of alkyl;
b) phenyl, substituted C1-C6by alkyl, -OR12, -O(CH2)mOCH3where m is 1-6, C2-C6alkenyl, C2-C6the quinil, halogen, ftor1-C6the alkyl, phenyl, -SCH3or C6-C10arils1-C6by alkyl;
in) naftanaila, possibly substituted C1-C6by alkyl, halogen or-OR12; or
g) carbocycle selected from saturated or partially saturated C5-C7cycloalkyl, possibly substituted C1 -C6by alkyl, -OR12C2-C6alkenyl, C2-C6the quinil, halogeno, ftor1-C6the alkyl or C6-C10arils1-C6by alkyl;
provided that R11is not 3,4,5-tri-methoxyphenyl.

2. The compound according to claim 1, where R11is:
phenyl, substituted C1-C6by alkyl, -OR12, -O(CH2)mOCH3where m is 1-6, C2-C6alkenyl, C2-C6the quinil, halogen, ftor1-C6the alkyl, phenyl, -SCH3or C6-C10arils1-C6by alkyl;
naftaniel, possibly substituted C1-C6by alkyl, halogen or-OR12; or
carbocycle selected from saturated or partially saturated C5-7cycloalkyl, possibly substituted C1-C6by alkyl, -OR12C2-C6alkenyl, C2-C6the quinil, halogeno, ftor1-C6the alkyl or C6-C10arils1-C6the alkyl.

3. The compound according to claim 2, having the structure of formula (D):
,
in isolated E or Z geometric isomer or a mixture of E - and Z-geometric isomers, in the form of tautomer or a mixture of tautomers, in the form of a stereoisomer or pharmaceutically acceptable salt, where
R1represents hydrogen;
R2is the Wallpaper hydrogen or C 1-C6alkyl;
R3, R4, R5and R6are the same or different and independently represent hydrogen, halogen, -OR12or C1-C6alkyl;
R7represents hydrogen or C1-C6alkyl;
R8represents hydrogen;
each R12independently represents hydrogen or C1-C6alkyl;
R14and R15are the same or different and independently selected from hydrogen, fluorescent, methyl, ethyl, trifloromethyl, -OH, -OCH3or-NH2; or R14and R15together form oxo;
R16and R17are the same or different and independently represent hydrogen, halogen, C1-C6alkyl or-OR12; or R16and R17together form oxo;
t is 0, 1, 2 or 3; and
each R20is the same or different and independently represents a C1-C6alkyl, -OR12C2-C6alkenyl, C2-C6quinil, halogeno, ftor1-C6alkyl, phenyl, -SCH3or C6-C10arils1-C6alkyl.

4. The compound according to claim 2, where R11represents naftaniel, substituted OR12where R12represents hydrogen or C1-C6alkyl.

5. The compound according to claim 2, where R11represents carbocyclic selected from saturated is whether partially saturated C 5-C7cycloalkyl.

6. The compound according to claim 5, where R11represents a 5-, 6 - or 7-membered cycloalkenyl.

7. The connection according to claim 6, having a structure of formula (W):

in isolated E or Z geometric isomer or a mixture of E - and Z-geometric isomers, in the form of tautomer or a mixture of tautomers, in the form of a stereoisomer or pharmaceutically acceptable salt, where
R1represents hydrogen;
R2represents hydrogen or C1-C6alkyl;
R3, R4, R5and R6are the same or different and independently represent hydrogen, halogen, -OR12or C1-C6alkyl;
R7represents hydrogen or C1-C6alkyl;
R8represents hydrogen;
R9represents hydrogen, C1-C6alkyl or-C(=O)R13;
R10represents hydrogen or C1-C6alkyl;
each R12independently represents hydrogen or C1-C6alkyl;
each R13independently represents a C1-C6alkyl;
R14and R15are the same or different and independently selected from hydrogen, fluorescent, methyl, ethyl, trifloromethyl, -OH, -OCH3or-NH2; or R14and R15together form oxo;
R16and R17ablauts the same or different and independently represent hydrogen, halogen, C1-C6alkyl or-OR12; or R16and R17together form oxo;
may, R14and R16together form a direct bond, thus forming a double bond connecting W and Y; or R14and R16together form a direct bond, and R15and R17together form a direct bond, thus forming a triple bond connecting W and Y;
p is 0, 1, 2 or 3; and
each R21is the same or different with respect to each and independently represents a C1-C6alkyl, -OR12C2-C6alkenyl, C2-C6quinil, halogeno, ftor1-C6alkyl or C6-C10arils1-C6alkyl.

8. The connection according to claim 7, where each of R9and R10represents hydrogen.

9. The connection of claim 8, where
each of R1and R2represents hydrogen;
p is 0, 1, 2 or 3;
each R21independently represents a C1-C6alkyl, halogeno or ptors1-C6alkyl; and
each of R3, R4, R5and R6independently represents hydrogen, C1-C6alkyl, halogeno or12.

10. The connection according to claim 7, where R9represents a C1-C6alkyl, and R10represents hydrogen.

11. The connection of claim 10, where
each of R1and R2represents the t are hydrogen;
p is 0, 1, 2 or 3;
each R21independently represents a C1-C6alkyl, halogeno or ptors1-C6alkyl; and
each of R3, R4, R5and R6independently represents hydrogen, C1-C6alkyl, halogeno or12.

12. The connection according to claim 7, where
R7represents hydrogen or C1-C6alkyl;
R8represents hydrogen;
each of R16and R17independently represents hydrogen, halogen, C1-C6alkyl or-OR12where R12independently represents hydrogen or C1-C6alkyl; and R14and R15together form oxo.

13. The compound according to claim 2, where R11represents a C1-C6alkyl and each of R9and R10represents hydrogen.

14. A compound selected from:
(E)-3-(3-(2,6-dimethylstyryl)phenyl)propan-1-amine;
(Z)-3-(3-(2,6-dimethylstyryl)phenyl)propan-1-amine;
(E)-3-(3-(2-methylstyryl)phenyl)propan-1-amine;
(Z)-3-(3-(2-methylstyryl)phenyl)propan-1-amine;
(E)-3-(3-(2,6-dimethylstyryl)-2-were)propan-1-amine;
(Z)-3-(3-(2,6-dimethylstyryl)-2-were)propan-1-amine;
(E/Z)-3-(3-(2-ethyl-6-methylstyryl)phenyl)propan-1-amine;
(E/Z)-3-(3-(2,5-dimethylstyryl)phenyl)propan-1-amine;
(E/Z)-3-(3-(2,4-dimethylstyryl)phenyl)propan-1-amine;
(E)-3-(3-(2,4,6-trimethylsilyl)phenyl)propan-1-amine;
(E/Z)-3-(3-(2-these is styryl)phenyl)propan-1-amine;
(E/Z)-3-(3-(2-eministry)phenyl)propan-1-amine;
(E/Z)-3-(3-(3,4-dimethylstyryl)phenyl)propan-1-amine;
(E/Z)-3-(3-(2-isopropylthio)phenyl)propan-1-amine;
(E/Z)-4-(3-(3,5-dimethylstyryl)phenyl)propan-1-amine;
(E/Z)-4-(3-(2-methoxystyrene)phenyl)propan-1-amine;
(E)-3-(3-(2,6-dichlorostyrene)phenyl)propan-1-amine;
(E/Z)-3-(3-(2,3-dimethylstyryl)phenyl)propan-1-amine;
(E)-3-(3-(2,6-dimethylstyryl)-4-forfinal)propan-1-amine;
(E/Z)-3-(3-(2-(trifluoromethyl)styryl)phenyl)propan-1-amine;
(E)-3-(3-(2,6-dimethoxymethyl)phenyl)propan-1-amine;
(E)-3-(3-(2,6-bis(trifluoromethyl)styryl)phenyl)propan-1-amine;
(E)-3-amino-1-(3-(2,6-dichlorostyrene)phenyl)propan-1-ol;
(E)-3-amino-1-(3-(2-chloro-6-methylstyryl)phenyl)propan-1-ol;
(E)-2-(3-(3-aminopropyl)styryl)phenol;
(E)-3-(5-(2,6-dichlorostyrene)-2-methoxyphenyl)propan-1-amine;
(R,E)-1-amino-3-(3-(2,6-dichlorostyrene)phenyl)propan-2-ol;
(S,E)-1-amino-3-(3-(2,6-dichlorostyrene)phenyl)propan-2-ol;
(E/Z)-(3-(3-(2,6-diatoxanthin)phenyl)propan-1-amine;
(E)-3-(3-(2-amoxicill)phenyl)propan-1-amine;
(E/Z)-3-(3-(2-isopropoxycarbonyl)phenyl)propan-1-amine;
(E)-3-amino-1-(3-(2,6-dichlorostyrene)phenyl)propane-1-it;
(E)-1-amino-3-(3-(2,6-dichlorostyrene)phenyl)propan-2-it;
(R,E)-3-amino-1-(3-(2,6-dichlorostyrene)phenyl)propan-1-ol;
(S,E)-3-amino-1-(3-(2,6-dichlorostyrene)phenyl)propan-1-ol;
(S,E)-3-(3-(2,6-dichlorostyrene)phenyl)-2-forproper-1-amine;
(E)-3-(3-(2,6-dichlorostyrene)phenyl)-2,2-ditropan-1-amine;
(Z)-3-(3-(2-(2-methoxyethoxy)styryl)is enyl)-propan-1-amine;
(E)-3-(3-(3-methoxystyrene)phenyl)propan-1-amine;
(Z)-3-(3-(4-chlorostyryl)phenyl)propan-1-amine;
(E)-3-(3-(2-(biphenyl-2-yl)vinyl)phenyl)propan-1-amine;
(E)-3-(3-(3-chlorostyryl)phenyl)propan-1-amine;
(E)-3-(3-(2-butoxyethyl)phenyl)propan-1-amine;
(E)-3-(3-(4-methoxystyrene)phenyl)propan-1-amine;
(Z)-3-(3-(2-propoxyethyl)phenyl)propan-1-amine;
(E)-3-(5-(2-chloro-6-(methylthio)styryl)-2-methoxyphenyl)propan-1-amine;
(E)-3-(3-(2-(1-methoxynaphthalene-2-yl)vinyl)phenyl)propan-1-amine;
(Z)-3-(3-(2-(naphthalene-1-yl)vinyl)phenyl)propan-1-amine;
(Z)-3-(3-(2-(3-methoxynaphthalene-2-yl)vinyl)phenyl)propan-1-amine;
(E/Z)-3-(3-(2-(2-methoxynaphthalene-1-yl)vinyl)phenyl)propan-1-amine;
(E)-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-amine;
(E)-3-amino-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-ol;
(S,E)-3-amino-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-ol;
(R,E)-3-amino-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-ol;
(E)-2-methyl-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-amine;
(E)-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)butane-1-amine;
(E)-3-(2-methyl-5-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-amine;
(E/Z)-4-amino-2-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)butane-2-ol;
(E)-3-fluoro-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-amine;
(E)-4-amino-1,1,1-Cryptor-2-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)butane-2-ol;
(E-3-amino-2,2-dimethyl-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-ol;
(E)-3-amino-2-methyl-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-ol;
(E)-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propane-1,3-diamine;
(E)-4,4,4-Cryptor-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)butane-1-amine;
(E)-3-methoxy-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-amine;
(E)-4-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)butane-2-amine;
(E)-1-amino-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-2-ol;
(E)-2-(3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propylamino)ethanol;
(E)-3-methoxy-N-methyl-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-amine;
(E)-3-amino-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-it;
(E)-3-amino-2,2-dimethyl-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-it;
(E)-3-amino-2-methyl-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-it;
(E)-3-amino-2-fluoro-1-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)propan-1-it;
(E)-2-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenoxy)ethanamine;
(E)-2-amino-N-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)ndimethylacetamide;
(E)-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)prop-2-in-1-amine;
(E)-2-fluoro-3-(3-((E)-2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)prop-2-EN-1-amine;
(E)-3-(3-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)prop-2-in-1-amine;
(E)-2-fluoro-3-(3-((E)-2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)phenyl)prop-2-EN-1-amine;
(E)-3-(3-(the UNT-1-enyl)phenyl)propan-1-amine;
(E)-3-(3-(hept-1-enyl)phenyl)propan-1-amine;
(E)-3-(3-(non-4-EN-5-yl)phenyl)propan-1-amine;
(E)-4-(3-(3-aminopropyl)phenyl)-2-methylbut-3-EN-2-ol;
(E)-4-(3-(3-aminopropyl)styryl)heptane-4-ol;
(E)-1-(3-(3-aminopropyl)phenyl)Gex-1-EN-3-ol;
(E)-1-(3-(3-aminopropyl)phenyl)-3-ethylpent-1-EN-3-ol;
(E)-3-(3-(3-aminopropyl)phenyl)prop-2-EN-1-ol;
(E)-3-(3-(3-methoxypropyl-1-enyl)phenyl)propan-1-amine;
(E)-1-(3-(3-aminopropyl)phenyl)-3-metrex-1-EN-3-ol and
(E)-1-(3-(3-aminopropyl)phenyl)-3-ethylhex-1-EN-3-ol.

15. Pharmaceutical composition for treatment of ophthalmic diseases or disorders, containing a pharmaceutically acceptable carrier and a compound according to any one of claims 1 to 14 in an effective amount.

16. The pharmaceutical composition according to § 15 for the treatment of ophthalmic diseases or disorders in a subject.

17. The pharmaceutical composition according to clause 16, where the ophthalmic disease or disorder is an age-related macular degeneration or macular dystrophy, Stargardt.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing cyclohexane and derivatives thereof of general formula R=H, . The method involves producing saturated hydrocarbons and derivatives thereof, which can be used as semi-products in organic synthesis. The method involves hydrogenation of cyclohexene or a derivative thereof, which is selected from 1-(N-piperidino)cyclohexene-1,1-(N-morpholino)cyclohexene-1 or 1,4-dicyclohex-1-enylpiperazine with hydrogen gas at atmospheric pressure of hydrogen in the presence of a nanocatalyst in tetrahydrofuran medium at temperature of 50-70°C for 5-6 hours, followed by extraction of the end product. The nanocatalyst used is nickel nanoparticles which are obtained by reducing nickel (II) chloride with lithium aluminium hydride in situ. The method can also be used to obtain a wider range of cyclohexane derivatives which contain heterocyclic groups.

EFFECT: method enables to conduct the process at atmospheric pressure using a catalyst obtained using a simpler technique, which simplifies the method overall.

4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a heterocyclic compound, involving: reaction of a mixture of 1-methylpiperazine and 5-halogen-2-nitroaniline in a first solvent and at a first temperature ranging from approximately 90°C to approximately 110°C to obtain a compound of formula where the first solvent contains alcohol; cooling the mixture containing the compound of formula VIH to a second temperature ranging from approximately 85°C to approximately 95°C; adding a volume of a second solvent which is different from the first solvent to the mixture, where the second solvent contains water; and forming a suspension of the compound of formula VIH; where the second solvent is heated to the second temperature. The invention also relates to methods of producing a compound of formula VIH using other solvents such as heptane and HO-(CH2)q-OH or HO-CH2CH2OCH2CH2-OH, where q is selected from 2, 3 or 4.

EFFECT: novel method of producing a compound of formula VIH, which enables to obtain a highly pure product which does not require additional purification and is more suitable for use on a large scale owing to the solvents used.

74 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing cycloalkylamines of general formula Alk-R, where

, , , , , , , , , . The method is realised by reacting a cyclic ketone with an amine derivative and formic acid in the presence of a catalyst. The cyclic ketones used include cyclopentanone, cyclohexanone and 2-adamantanone, and the amine derivative used is formamide, cyclohexylamine, piperidine, morpholine, piperazine, 2-aminoethanol, 1,2-ethylenediamine, and the catalyst used is copper nanoparticles. The process is carried out in molar ratio ketone: amine derivative: HCOOH equal to 1:3-4:5-10, at temperature 100°C for 3-9 hours. The copper nanoparticles can be obtained in situ, as well as beforehand.

EFFECT: high output of cycloalkylamines under milder conditions for carrying out the process.

3 cl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new chemical compound - N-1-[(4-fluorophenyl)-2-(1-ethyl-4-piperidyl)-ethyl]-4-nitrobenzamide hydrochloride of formula Also, the invention refers to drugs.

EFFECT: preparation of a new biologically active compound which exhibits antiarhythmic and antifibrillatory activity.

2 cl, 1 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to application in an effective amount and to new nicotine receptor agonists described by general formula (i) or (ii) for treating inflammatory diseases chosen from a group including asthma, chronic obstructive pulmonary disease (COPD), interstitial pulmonary tissue fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis (HP), chronic hypersensitivity pneumonitis and bronchiolitis obliterans organising pneumonia (BOOP). The compounds (i) and compounds (ii) relate to formulae (i) (ii) where in formula (i) R1 and R2 independently mean alkyl with 1-10 carbon atoms; Xa means CH or N; Ya means one or more substitutes chosen from hydrogen, halogen, cyano, hydroxyl, alkyl with 1-10 carbon atoms optionally substituted with one or more halogen atoms, and alkoxy with 1-10 carbon atoms; n means an integer 0 or 2; J means a counterion representing a compound for maintaining electric neutrality, e.g., halogen, sulphate, sulphonate; in formula (ii) R3 is chosen from or Xb means N or N+-R10; R4 means one or more substitutes chosen from hydrogen, halogen; each R10, R11 and R12 independently means alkyl with 1-10 carbon atoms; provided the presence of the counterion when Xb means N+-R10.

EFFECT: use of nicotine receptor agonists in the effective amount for treating inflammatory diseases.

26 cl, 40 dwg, 3 tbl, 38 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for synthesis of 1-aminomethyl-2-phenylacetylenes of formula (1), where is characterised by that, phenylacetylene (Ph-C≡CH) is reacted with gem-diamines R2NCH2NR2, where R2N is as defined above, in the presence of a Sm(NO3)2*6H2O catalyst in molar ratio phenylacetylene: gem-diamine: Sm(NO3)2*6H2O=10:(8-12):(0.2-0.6) at 80°C and atmospheric pressure for 3-5 hours.

EFFECT: new method is designed for synthesis of 1-aminomethyl-2-phenylacetylenes, which can be used in fine organic synthesis, particularly for synthesis of scarce polycyclic compounds.

1 tbl, 1 ex

FIELD: chemistry.

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

EFFECT: new compounds have useful biological activity.

8 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining substituted aminobenzhydrols, which can be used as semi-products in synthesis of medications of general formula , where: R1=R3=H, R2=NH2, R4=Cl (1); R1=R3=H, R2=NH2, R4=Br (2); R1=R3=H, R2=NH2, R4=OCH3 (3); R1=R4=H, R2=NH2, R3=Cl (4); R1=H, R2=NH2, R3=Cl, R4=Cl (5); R1=NH2, R2=Cl, R3=R4=H (6); R1=NH2, , R3=R4=H (7); R1=NH2, R2=Cl, R3=H, R4=Cl (8); R1=NH2, , R3=H, R4=Cl (9); R1=NH2, R3=Cl, R2=R4=H (10); R1=NH2, , R2=R4=H (11); R1=NH2, R2=H, R3=Cl, R4=Cl (12); R1=NH2, R2=H, , R4=Cl (13), whish lies in simultaneous reduction of nitro- and carbonyl groups of respective nitrobenzphenones of general formula , where: R1=R3=H, R2=NO2, R4=Cl; R1=R3=H, R2=NO2, R4=Br; R1=R3=H, R2=NO2, R4=OCH3; R1=R4=H, R2=NO2, R3=Cl; R1=H, R2=NO2, R3=Cl, R4=Cl; R,=NO2, R2=Cl, R3=R4=H; R1=NO2, , R3=R4=H; R1=NO2, R2=Cl, R3=H, R4=Cl; R1=NO2, , R3=H, R4=Cl; R1=NO2, R3=Cl, R2=R4=H; R1=NO2, , R2=R4=H; R1=NO2, R2=H, R3=Cl, R4=Cl; R1=NO2, R2=H, , R4=Cl, reducing system Zn-NaBH4 in alcohol with molar ratio of substratum : zinc: sodium tetrahydroborate equal 1 : 3.5 : 0.25.

EFFECT: reduction of synthesis cost, reduction of time and temperature for process carrying out, increase of target products output.

1 cl, 2 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: present invention concerns the salts containing bis(trifluoromethyl)imide anions and saturated, partially or completely unsaturated heterocyclic cations, method of production and application thereof as ionic liquids.

EFFECT: production of new salts to be used as ionic liquids.

19 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: inventive subject matter is compouns and their pharmaceutically acceptable salts which can be applied in prevention and treatment of diseases caused by HCV infection. Structural formulae of the compounds are presented in the claim.

EFFECT: obtaining anti-HCV medicine including the claimed compound or its pharmaceutically acceptable salt as active component.

2 cl, 100 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1,3-dicarbonyl derivatives of adamantane of general formula I where R=H, X=OH, OMe, OEt, OPri, OBus, OCH2CH(Et)Bu, OCH2CF3, OCH(CH3)CF3, OCH2CF2CF2H, OCH2CH2CH2Br, OCH2C=CH, NEt2, NC5H10 (piperdyl), NC4H8O (morpholyl), C6H5NH, C6H4OMe, C4H3O (furyl); R=Me, X-OH, Me, OMe, O-Pri, X=NC4H8O (morpholyl), C4H3O (furtyl), NEt2, C6H5NH, C6H4OMe; involving carbonylation of an adamantane compound in the presence of electrophilic catalysts, where the adamantane compound used is adamantane or 1,3-dimethyladamantane and carbonylation is carried out under the action of CO at atmospheric pressure in a solution of CH2Br2 at temperature of 0-25°C for 0.5-3 hours, and the catalyst used is a super-electrophilic CBr4·2AlBr3 complex, in molar ratio [CBr4-2AlBr3]: [adamantane compound] = (1.5-2):1, and a nucleophilic substrate - water or alcohol - is added to the carbonyl derivative formed in situ, without extraction thereof, in an atmosphere of CO, said substrate containing an alkyl or acetylene or bromoalkyl or polyfluoroalkyl group; or an amine of an aliphatic or heterocyclic or aromatic series; or an aromatic hydrocarbon or an aromatic heterocycle; and reaction with a nucleophile is carried out at temperature of 0-25°C.

EFFECT: single-step method of producing 1,3-dicarbonyl derivatives of adamantanes with two identical carbonyl-containing groups in nodal positions of the adamantane nucleus enables to use readily available adamantane compounds as starting compounds.

25 ex

FIELD: medicine.

SUBSTANCE: invention refers to a method of treating neurodegenerative disorders, neuropsychiatric disorders, as well as psychosis secondary to neurodegenerative disorders by introducing a compound of formula or its tartrate salt into a patient.

EFFECT: treating neurodegenerative disorders, neuropsychiatric disorders, psychosis secondary to neurodegenerative disorders by introducing the compound of formula representing the properties of the inverse 5-HT2A and 5-HT2C receptor agonist, or its tartrate salt.

15 cl, 3 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent having CXCR2 inhibiting properties. In formula I , X denotes -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- or -S-; R3, R4, R5 and R6 independently denote hydrogen, F, CI, Br, I; R7 denotes hydrogen; Y1, Y2, Y3 and Y4 independently denote -CR8- or nitrogen, provided that at least two of Y1, Y2, Y3 and Y4 denote -CR8-; where R8 denotes hydrogen, F, CI, Br, I; A denotes a cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; a bicyclic partially saturated 9-member cycloalkyl; a bicyclic partially saturated 9-10-member heterocycle in which two atoms in the ring are oxygen atoms; phenyl; naphthyl; a 5-6-member heteroaryl in which 1-3 atoms in the ring are oxygen, sulphur and nitrogen atoms; a 9-10-member bicyclic heteroaryl in which 1-3 atoms in the ring are nitrogen, oxygen and sulphur atoms; a 6-member heterocycle in which one atom in the ring is a nitrogen atom and which can be unsubstituted or substituted with alkyl having 1, 2, 3 or 4 carbon atoms, -C(O)CH3, -C(O)CH2CH3, -C(O)cyclopropyl, -C(O)CF3 and -C(O)OC(CH3)3; where phenyl, heterocyclic or heteroaryl radical is substituted with 1, 2 or 3 radicals selected from a group consisting of F, O, Br, I, OH, CN, NO2, SCF3, SF3, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; cycloalkyl having 3, 4, 5 or 6 carbon atoms; alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -NR9R10, C(O)R44, S(O)SR47, -(CH2)k-phenyl, 5-6-member heteroaryl, in which 1-3 atoms in the ring are nitrogen and sulphur atoms; where the phenyl radical may be substituted with F, CI, Br, I; R9 is an alkyl having 1, 2, 3 or 4 carbon atoms; R10 is an alkyl having 1, 2, 3 or 4 carbon atoms; R44 is an alkyl having 1, 2, 3 or 4 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; alkoxy having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms; R47 is an alkyl having 1, 2, 3 or 4 carbon atoms; k equals 0, 1, 2 or 3; s equals 1 or 2; B is -O-C(R11R12), -C≡C-, -CR52=CR53-, -C(R13R14)C(R15R16), -NR17-C(R18R19); R11, R12, R13, R14, R15, R16, R17, R18, R19, R52, R53 independently denote hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; D is C(O)OH, C(O)NHR21 or C(=NR58)NHR22; R21 and R22 independently denote hydrogen, -SO2-alkyl having 1, 2, 3 or 4 carbon atoms, -SO2-phenyl; R58 is OH; R1 and R2 independently denote an alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where the alkyl radicals are unsubstituted or substituted with 1 radical selected from a group consisting of F, Cl, Br, I, phenyl substituted with OH; or R1 and R2, taken together with a carbon atom with which they are bonded form a 3-, 4-, 5- or 6-member carbocycle. The invention also relates to use of formula I compounds in preparing a medicinal agent which has CXCR2 inhibiting properties, to a medicinal agent which containing an effective amount of the disclosed compound and having CXCR2 inhibiting properties, as well as to use of formula II compounds (formula and values of radicals are given in the formula of invention) in preparing a medicinal agent having CXCR2 inhibiting properties.

EFFECT: high effectiveness of application.

10 cl, 384 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the compound with formula (I) or to its tartrate salt. The invention also relates to application of the composition as well as the method of inhibiting of monoamine receptor activation to inverse agonist and anti-dyskinesia agent in the combination with inverse agonist.

EFFECT: production of the new biologically active compound having inverse agonist activity of serotonin receptor.

54 cl, 7 ex, 3 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel α-(N-sulfonamido)acetamides of the formula (I) or their optical isomers wherein values R1, R, R2 and R3 are given in the invention claim. Proposed compounds are inhibitors of production of β-amyloid peptide and can be used for inhibition of production of β-amyloid peptide. Also, invention relates to pharmaceutical composition based on these compounds and to a method for inhibition of production of β-amyloid peptide.

EFFECT: valuable medicinal property of compounds and pharmaceutical composition.

22 cl, 23 sch, 4 tbl, 501 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of (R)-2-arylpropionamide of the formula (I): , wherein Ar means aryl of the formula (IIIb): F-Arb wherein Arb means phenyl mono- or poly-substituted with the following groups: chlorine, fluorine atom; F means hydrogen atom, linear or branched (C1-C5)-alkyl residue, benzoyl, 2,6-dichlorophenylamino-, 2,6-dichloro-3-methylphenylamino-group; R means hydrogen atom, (C1-C4)-alkyl; X means linear or branched (C1-C6)-alkylene optionally substituted with the group -CO2R4 wherein R4 means hydrogen atom or linear or branched (C1-C6)-alkyl group, phenyl or phenylmethylene group; R1, R2 and R3 mean independently linear or branched (C1-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C6)-alkenyl, aryl, aryl-(C1-C3)-alkyl, or R1 and R2 in common with nitrogen atom (N) to which they are attached form nitrogen-containing 6-membered heterocyclic ring of the formula (II) , and R3 has values indicated above independently wherein in the formula (II) Y means a simple bond, methylene group, oxygen atom, nitrogen atom or sulfur atom; p means a whole number 2; Z- means a pharmaceutically acceptable counterion of quaternary ammonium salts. Also, invention relates to using compound of the formula (I) in treatment of psoriasis, pemphigus and pemphigoid, rheumatic arthritis, intestine chronic inflammatory pathology including ulcerous colitis, acute respiratory distress-syndrome, idiopathic fibrosis, mucoviscidosis, pulmonary chronic obstructive disease and glomerulonephritis, and also for prophylaxis and treatment of injure caused by ischemia and reprefusion. Also, invention relates to a pharmaceutical composition possessing the inhibitory activity with respect to chemotaxis of polymorphonuclear leukocytes and monocytes induced by complement C5a fractions and comprising compound of the formula (I) in mixture with a suitable carrier. Also, invention relates to a method for synthesis of compounds of (R)-2-arylpropionamide of the formula (I) that involves interaction of amides of the formula (IV) given in the invention description with compounds of the formula R3Zwherein Z means a leaving group, such as chloride, bromide, iodide, methanesulfonate, p-toluenesulfonate, sulfate. Invention provides synthesis of (R)-2-arylpropionic acid omega-aminoalkylamide quaternary ammonium salts used for inhibition of chemotaxis activation induced by the C5a complement component.

EFFECT: valuable properties of compounds and pharmaceutical compositions.

17 cl, 1 tbl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein Ar represents phenyl substituted with a group taken among isobutyl, benzoyl, isopropyl, styryl, pentyl, (2,6-dichlorophenyl)-amino-group, α-hydroxyethyl, α-hydroxybenzyl, α-methylbenzyl and α-hydroxy-α-methylbenzyl; R represents hydrogen atom; X means linear (C1-C6)-alkylene, (C4-C6)-alkenylene, (C4-C6)-alkynylene optionally substituted with group -CO2R3 wherein R3 means hydrogen atom, group (CH2)m-B-(CH2)n wherein B means oxygen atom; m = 0; n means a whole number 2; or B means group -CONH; m means a whole number 1; n means a whole number 2 and so on; R1 and R2 are taken independently among group comprising hydrogen atom, linear (C1-C4)-alkyl, hydroxy-(C2-C3)-alkyl and so on. Invention proposes a method for preparing compounds of the formula (I). Invention proposes inhibitors of C5-induced hemotaxis of polymorphonuclear leukocytes and monocytes representing (R)-2-arylpropionic acid omega-aminoalkylamides of the formula (I). Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to hemotaxis of polymorphonuclear leukocytes and monocytes and comprising compounds of the formula (I) in mixture with suitable carrier. Proposes (R)-2-arylpropionic acid omega-alkylamides are useful for inhibition of hemotaxic activation induced C5a and other hemotaxic proteins.

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

18 cl, 3 tbl, 23 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of nitrogen-containing heterocyclic compounds of the general formula (I'):

wherein R represents the group:

m = 0-3; R1 represents halogen atom, cyano-group and others; X represents oxygen or sulfur atom, or the group -CH2 and others; Z1 and Z2 represents the group -CH2 and others; Q represents oxygen or sulfur atom, or the group -CH2 or -NH; R2 represents substituted phenyl; n = 0-2; R3 represents (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl group and others; R4, R5, R6 and R7 represent hydrogen atom or (C1-C6)-alkyl and others; R8 represents hydrogen atom, (C1-C6)-alkyl. Compounds of the formula (I') possess of activity modulating activity of chemokine MIP-1α receptors and can be used in medicine in treatment of inflammatory diseases and respiratory ways diseases.

EFFECT: improved preparing method, improved methods for treatment, valuable medicinal properties of compounds and composition.

20 cl, 283 ex

The invention relates to a new group of individual chemical compounds - cyclic amino compounds represented by the following formula:

< / BR>
where R1represents a phenyl group which may be optionally substituted by at least one Deputy, which represents a halogen atom; R2represents a C1-C8aliphatic acyl group or (C1-C4alkoxy) carbonyl group; and R3represents a saturated cyclic amino group which has from 2 to 8 carbon atoms in one or more cycles, with the highest nitrogen cycle has from 3 to 7 atoms in the cycle, and the specified saturated cyclic amino group substituted by a group having the formula-S-S-R4where R4and X have the meanings as defined below, and the said saturated cyclic amino group attached via its cyclic nitrogen atom adjacent to the carbon atom that is attached to the substituents R2and R1; R4represents a phenyl group which may be optionally substituted by at least one Deputy, selected IGP and nitro groups; WITH1-C6alkyl group which may be optionally substituted by at least one Deputy, selected from the group consisting of amino groups, carboxyl groups, (C1-C4alkoxy)carbonyl groups, substituents having the formula-NH-A1(where a1represents an-amino acid residue), and substituents having the formula-CO-AND2(where a2represents an-amino acid residue); or (C3-C8cycloalkyl group, and X represents a sulfur atom, sulfinol group or sulfonyloxy group, and the above-mentioned cyclic aminecontaining group may be optionally additionally substituted by a group having the formula = CR5R6where R5and R6are the same or different, and each independently represents a hydrogen atom, a carboxyl group, (C1-C4alkoxy)carbonyl group, karbamoilnuyu group, (C1-C4alkyl) karbamoilnuyu group or di-(C1-C4alkyl)karbamoilnuyu group; or their pharmacologically acceptable salts, pharmaceutical composition having inhibitory action in Rel is the prevention of disease, selected from the group consisting of embolism and thrombosis in a warm-blooded animal

The invention relates to new derivatives of biphenylamine formula (I)

< / BR>
where a IS-O-CmH2m-X1-

or denotes the formula (II)

,

where X1oxygen,

or formula (III)

< / BR>
R1- cycloalkyl with 5-7 carbon atoms, Ar1, CR4R5AG2, (CH3)2R6, R2is hydrogen, alkyl, hydroxyl, halogen, O - alkyl, R3is hydrogen, alkyl, R4- alkyl, trifluoromethyl, CH2HE, R5is hydrogen, alkyl, trifluoromethyl, or R4and R5may together form alkylene, R6- CH2OH, CONR7R8CH2R7R8provided that R1means associated through alkylene unsubstituted phenyl residue, or their acid additive salts with pharmacologically acceptable acids

FIELD: chemistry.

SUBSTANCE: invention concerns novel aryl pyrrolidines of formula I:

, where X, which can be identical or different, denote halogen, halogen-C1-6alkyl, NO2, C1-6alkyl, C1-6alkoxy, CN, halogen-C1-6alkoxy, C1-6alkylthio, C1-6alkylthionyl, C1-6alkylsulphonyl, halogen- C1-6alkylthio, halogen- C1-6alkylthionyl, halogen- C1-6alkylsulphonyl, OH, mercapto groups, NH2, C1-6alkylcarbonyl amino groups, halogen- C1-6alkylcarbonyl-amino, C1-6alkoxycarbonyl amino groups, halogen-C1-6alkoxycarbonylamino; Y, which can be identical or different, denote halogen, halogen- C1-6alkyl, NO2, C1-6alkyl, C1-6alkoxy, CN, halogen- C1-6alkoxy, C1-6alkylthio, C1-6alkylthionyl, C1-6alkylsulphonyl, halogen- C1-6alkylthio, halogen- C1-6alkylthionyl, halogen- C1-6alkylsulphonyl, hydroxyl groups, mercapto groups, NH2, C1-6alkylcarbonyl amino groups, halogen- C1-6alkylcarbonyl amino, C1-6alkoxycarbonyl amino groups, halogen- C1-6alkoxycarbonyl amino; R denotes halogen- C1-6alkyl; m equals 0, 1, 2, 3, 4, 5; n equals 1, 2, 3, 4; G denotes a group: , where R1 and R2 each independently denotes H, unsubstituted C1-6alkyl, halogen- C1-6alkyl, -CH2R7;R3, R4 each independently denotes H; I equals 1, 2, 3; R5 denotes H; R6 denotes C1-6alkylcarbonyl, a group: G6 - G8:

b where k3 equals 0; k4 equals 0; R7 denotes an unsubstituted 6-member heteroaryl with one N; A denotes C, N.

EFFECT: compounds exhibit insecticidal activity, which enables use thereof in insect and/or tick control method.

7 cl, 13 tbl, 8 ex

Up!