Novel disubstituted phenylpyrrolidines as modulators of cortical catecholaminergic neurotransmission

FIELD: chemistry.

SUBSTANCE: invention relates to novel disubstituted phenylpyrrolidines of formula , any stereoisomers thereof or any mixtures of stereoisomers thereof, or N-oxides thereof, or pharmaceutically acceptable salts thereof, where Ar denotes phenyl; R1 denotes F, Cl; R2 denotes F and Cl; R3 denotes H, Me, Et, n-Pr, iso-Pr, n-Bu, iso-Bu, sec-Bu, tert-Bu, cyclopropylmethyl, CFH2CH2CH2-, CF2HCH2CH2-, CF3CH2CH2-, allyl and CH3OCH2CH2-; X denotes F, OH; under the condition that X denotes OH, R3 does not denote H.

EFFECT: compounds are capable of increasing levels of dopamine, norepinephrine and serotonin, which enables their use in treating central nervous system disorders.

16 cl, 21 dwg, 69 ex

 

The text descriptions are given in facsimile form.

1. The compound of the Formula (2):

any of its stereoisomers or any mixture of its stereoisomers, or its N-oxide, or pharmaceutically acceptable salt, where
Ar represents phenyl; R1selected from the group consisting of F and Cl; R2selected from the group consisting of F and Cl;
R3selected from the group consisting of H, Me, Et, n-Pr, ISO-Pr, n-Bu, ISO-Bu, sec-Bu, tert-Bu, cyclopropylmethyl, CFH2CH2CH2-, CF2HCH2CH2-, CF3CH2CH2-, allyl and CH3Och2CH2-; and
X is selected from the group consisting of F, or IT; provided that when X is a HE, R3is not H;

2. The compound according to claim 1 of Formula (3):

or Formula (4):

or the Formula (5):

or of the Formula (6):

where R1, R2, R3and X are such as defined in claim 1.

3. The compound according to claim 1, where R1is a F.

4. The compound according to claim 1, where R2represents F, and R3represents H or Me.

5. The compound according to claim 1, where R3is a Et or n-Pr.

6. The compound according to claim 1, where R3represents Me.

7. The compound according to claim 1 in (+)-enantiomeric form.

8. The compound according to claim 1 in the (-)-enantiomeric form.

9. The compound according to claim 1, which is a
(-)-3-(3,5-differenl)-1-ethylpyrrolidin-3-ol;
(+)-3-(3,5-differenl)-1-ethylpyrrolidin-3-ol;
3-(3-chlor-forfinal)-1-ethylpyrrolidin-3-ol;
3-(2,3-differenl)-1-ethylpyrrolidin-3-ol;
3-(3-chloro-5-forfinal)-1-ethylpyrrolidin-3-ol;
3-(3,5-dichlorophenyl)-1-ethylpyrrolidin-3-ol;
3-(3,4-differenl)-1-propylpyrrolidine-3-ol;
3-(3,5-differenl)-1-ethylpyrrolidin-3-ol;
3-(3,5-differenl)-1-propylpyrrolidine-3-ol;
3-(3,4-dichlorophenyl)-1-ethylpyrrolidin-3-ol;
3-(3,5-differenl)-3-fluoro-1-methylpyrrolidine;
3-(3,4-differenl)-1-ethylpyrrolidin-3-ol;
3-(3,5-differenl)-3-ftorpirimidinu;
3-(3,5-dichlorophenyl)-3-ftorpirimidinu;
3-(2,4-differenl)-1-methylpyrrolidine-3-ol;
3-(3,4-differenl)-1-methylpyrrolidine-3-ol;
3-(2,3-dichlorophenyl)-1-ethylpyrrolidin-3-ol;
3-(3,5-differenl)-1-methylpyrrolidine-3-ol;
3-(3-chloro-2-forfinal)-1-methylpyrrolidine-3-ol;
3-(3-chloro-2-forfinal)-1-ethylpyrrolidin-3-ol;
3-(3-chloro-4-forfinal)-1-propylpyrrolidine-3-ol;
3-(3-chloro-5-forfinal)-1-propylpyrrolidine-3-ol;
3-(2,3-differenl)-3-ftorpirimidinu;
(+)-3-(3,4-differenl)-1-ethylpyrrolidin-3-ol;
(-)-3-(3,4-differenl)-1-ethylpyrrolidin-3-ol;
3-(3-chloro-5-forfinal)-1-methylpyrrolidine-3-ol;
(+)-3-(3,4-differenl)-1-propylpyrrolidine-3-ol;
(-)-3-(3,4-differenl)-1-propylpyrrolidine-3-ol;
(+)-3-(3,5-differenl)-1-propylpyrrolidine-3-ol;
(-)-3-(3,5-differenl)-1-propylpyrrolidine-3-ol;
(-)-3-(3-chloro-5-forfinal)-1-ethylpyrrolidin-3-ol;
(-)-3-(2,3-differenl)-1-ethylpyrrolidin-3-ol;
(-)-3-(2,3-differenl)-1-propylpyrrolidine-3-ol;
(+)-3-(2,3-differenl)-1-ol is piperalin-3-ol;
(+)-3-(3-chloro-2-forfinal)-1-ethylpyrrolidin-3-ol;
(+)-3-(2,3-differenl)-1-ethylpyrrolidin-3-ol;
(-)-3-(3-chloro-2-forfinal)-1-ethylpyrrolidin-3-ol;
(-)-1-butyl-3-(2,3-differenl)pyrrolidin-3-ol;
(-)-3-(2,3-differenl)-1-isobutylpyrazine-3-ol;
(-)-3-(2,3-differenl)-1-methylpyrrolidine-3-ol;
(-)-1-allyl-3-(2,3-differenl)pyrrolidin-3-ol;
(-)-3-(2,3-differenl)-1-(2-methoxyethyl)pyrrolidin-3-ol;
(-)-1-butyl-3-(3,5-differenl)pyrrolidin-3-ol;
(-)-1-allyl-3-(3,5-differenl)pyrrolidin-3-ol;
(-)-3-(3,5-differenl)-1-(2-methoxyethyl)pyrrolidin-3-ol;
(-)-3-(3,5-differenl)-1-isobutylpyrazine-3-ol;
(-)-3-(3,5-differenl)-1-methylpyrrolidine-3-ol;
(-)-3-(2,3-differenl)-1-(3,3,3-cryptochromes)pyrrolidin-3-ol;
(-)-1-(cyclopropylmethyl)-3-(2,3-differenl)pyrrolidin-3-ol;
3-(3,4-differenl)-1-isopropylpyrimidine-3-ol;
(+)-1-butyl-3-(3,5-differenl)pyrrolidin-3-ol;
(+)-3-(3,5-differenl)-1-methylpyrrolidine-3-ol;
(+)-3-(3,5-differenl)-1-isobutylpyrazine-3-ol;
(+)-3-(3,5-differenl)-1-(2-methoxyethyl)pyrrolidin-3-ol;
(+)-1-allyl-3-(3,5-differenl)pyrrolidin-3-ol;
(+)-3-(3-chloro-2-forfinal)- 1-methylpyrrolidine-3-ol;
(-)-3-(3-chloro-2-forfinal)-1-methylpyrrolidine-3-ol;
(+)-1-butyl-3-(2,3-differenl)pyrrolidin-3-ol;
(+)-3-(2,3-differenl)-1-methylpyrrolidine-3-ol;
(+)-3-(2,3-differenl)-1-(2-methoxyethyl)pyrrolidin-3-ol;
(+)-3-(2,3-differenl)-1-isobutylpyrazine-3-ol;
(+)-1-allyl-3-(2,3-differenl)PI is Raiden-3-ol;
(+)-3-(2,3-differenl)-1-(3,3,3-cryptochromes)pyrrolidin-3-ol;
(+)-1-(cyclopropylmethyl)-3-(2,3-differenl)pyrrolidin-3-ol;
(-)-3-(3-chloro-5-forfinal)-1-methylpyrrolidine-3-ol;
(+)-3-(3-chloro-5-forfinal)-1-methylpyrrolidine-3-ol or
(+)-3-(3-chloro-5-forfinal)-1-ethylpyrrolidin-3-ol;
or its pharmaceutically acceptable salt.

10. The pharmaceutical composition is capable of increasing the levels of dopamine, norepinephrine and serotonin containing a therapeutically effective amount of a compound according to any one of claims 1 to 9, any of its stereoisomers or any mixture of its stereoisomers, or an N-oxide, or pharmaceutically acceptable salts, together with one or more pharmaceutically acceptable carriers or diluents.

11. The use of compounds according to any one of claims 1 to 9, any stereoisomer or any mixture of its stereoisomers, or an N-oxide, or its pharmaceutically acceptable salt for the manufacture of medicines that can increase the levels of dopamine, norepinephrine and serotonin.

12. The application of claim 11, where the drug is intended for the manufacture of pharmaceutical compositions that can increase the levels of dopamine, norepinephrine and serotonin, to treat, prevent or alleviate diseases or disorders of the Central nervous system of a mammal.

13. The application indicated in paragraph 12, where the disorder cent the social nervous system is a cognitive disorder, neurodegenerative disorder, dementia, age-related cognitive disturbance, developmental disorders, autism spectrum disorder, ADHD (attention deficit disorder with hyperactivity disorder), cognitive disorder, occurring in the form of part of the main symptoms of schizophrenia or schizophrenia.

14. The way to increase levels of dopamine, norepinephrine and serotonin in the treatment, prevention or alleviation of disorders of the Central nervous system of a living animal body, including a stage of introduction of such a living animal body in need, a therapeutically effective amount of a compound according to any one of claims 1 to 9, or any of its stereoisomers or any mixture of its stereoisomers, or an N-oxide, or its pharmaceutically acceptable salt.

15. The compound according to any one of claims 1 to 9, any of its stereoisomers or any mixture of its stereoisomers, or an N-oxide, or its pharmaceutically acceptable salt for use as a drug, can increase the levels of dopamine, norepinephrine and serotonin.

16. The compound according to any one of claims 1 to 9, any of its stereoisomers or any mixture of its stereoisomers, or an N-oxide, or pharmaceutically acceptable salt, can increase the levels of dopamine, norepinephrine and serotonin, for use in the treatment, prevention or alleviation of disease is, or disorder, or condition of a mammal, where the disease, disorder or condition is sensitive to increased dopaminergic function of the Central nervous system.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to indole derivatives or pharmaceutically acceptable salts thereof of general formula (1): , where values of R1, R2, m are given in claim 1.

EFFECT: compounds have inhibiting activity on IKKβ, which enables their use as a preventive or therapeutic agent for treating IKKβ mediated diseases.

26 cl, 1 tbl, 29 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition for treating diabetes, obesity or metabolic syndrome, which includes therapeutically efficient amount of (5-hydroxyadamantan-2-yl)amide of trans-2'-tret-butyl-2'H-[1,3']bipyrazolyl-4'-carboxylic acid or its pharmaceutically acceptable salts, and pharmaceutically acceptable carrier.

EFFECT: invention also relates to application of said compound for preparation of medication, intended for treatment of said diseases.

2 cl, 1 tbl, 99 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to 11-(piperazin-1-yl) dibenzo[b,f[1,4]oxazapine compounds of general formula specified below wherein the radicals are presented in the description, to their pharmaceutically acceptable salts and pharmaceutical compositions. There are also described methods for preparing said compounds.

EFFECT: compounds may be used for treating disorders, such as schizophrenia, resistant schizophrenia, bipolar disorder, psychotic depression, resistant depression, depressive conditions related to schizophrenia, treating resistant OCD, autism, senile dementia, psychotic dementia, L-DOPA-induced psychotic disorder, psychogenic polydipsia, psychotic symptoms of neurological disorders, sleeping disorders.

39 cl, 25 ex, 8 dwg

FIELD: medicine.

SUBSTANCE: invention relates to condensed bicyclic compounds, having affinity with mineralocorticoid receptor (VR) of formula [I] and formula [ii], as well as to pharmaceutical compositions on their basis. In general formula [I[ and [ii] ring A represents benzene ring, which has substituent R1, condensed with adjacent 6-membered heterocyclic ring, and said benzene ring additionally optionally is substituted with one or two substituent(s), selected from halogen atom and C1-8-alkyl group, R1 represents C1-8-alkylsulfonyl amino group or C1-8-alkyl aminosulfonyl group, R2 and R3 (a) are similar or different and represent group, selected from hydrogen atom, C1-8-alkyl group, and from 6- to 10-membered monocyclic or bicyclic aryl group (said aryl group is optionally substituted with halogen atom), (b) are combined with each other with formation of oxogroup or (c) are combined with each other on their ends together with adjacent carbon atom with formation of C3-10-cycloalkyl group, X represents the following group =N-, =C(R4)- or -CH(R4)-, R4 represents hydrogen atom, cyanogroup, halogen atom, C1-6-alkyl group, C2-6-alkenyl group, C3-10-dicloalkyl group, C1-7-alkanoyl group, carbamoyl group or C3-8cycloalkenyl group, Ar represents from 6- to 10-membered monocyclic or bicyclic aryl group, optionally containing one or several heteroatom(s), selected from sulphur atom, oxygen atom and nitrogen atom (said aryl group is optionally substituted with similar or different, one or two substituent(s), selected from halogen atom, cyanogroup, C1-8-alkyl group, trihalogen- C1-8-alkyl group and C1-8alkoxygroup), and dotted line represents presence or absence of double bond, Xa represents the following group =N- or =C(CN)-, RZ represents hydrogen atom or halogen atom, R25 and R35 represent alkyl group, and Ar3 represents phenyl group, optionally substituted with one or two group(s), which is(are) selected from halogen atom and trihalogenalkyl group.

EFFECT: compounds can be applied as antihypertensive medication.

15 cl, 18 tbl, 8 dwg, 71 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of dihydroquinone and dihydronaphthyridinone of formula (I) or to its pharmaceutically acceptable salts, in which X represents group CR11 or N; Y represents group -C(O)R3, oxazolyl or isoxazolyl; Z represents phenyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, pyridinyl, pyrimidinyl or pyrazolyl, and is substituted with groups R1 and R2; R1 and R2 each independently represents H, halogen, CN group, C1-6alkyl or group -Y1-Y2-Y3-R8, or R1 and R2 together form group -O(CH2)nO-, where n represents 1 or 2; Y1 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O), -S-, -SO2- or bond; Y2 represents heterocycloalkylene, C1-6alkylene or bond, where heterocycloalkylene stands for cycloalkylene group, in which one, two carbon atoms are substituted with heteroatoms O or N, where heterocycloalkylene group also contains, at least, two carbon atoms and cycloalkylene represents ; Y3 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O)-, -SO2- or bond; R8 represents H, C1-6alkyl, C1-6alkoxy, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, or group -NR9R10, where R8, different from H, is optionally substituted with C1-6alkyl, halogen, group -CF3 or group -OH; R9 and R10 each independently represents H or C1-6alkyl; R3 represents OH, C1-6alkyl, C1-6alkoxy, (C1-6alkoxy)-C1-6alkoxy; R4 represents C1-6alkyl, phenyl, cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, tetrahydropyranyl or tetrahydrothiophene 1,1 -dioxide, and is optionally substituted with C1-6alkyl, hydroxyl group, C1-6alkoxy, halogen, nitro group, amino group, cyano group or halo-lower alkyl; R5 and R6 each independently represents H, halogen, C1-6alkyl, group -CF3, C1-6alkoxy; R7 represents H; R11 represents H. Invention also re4lates to pharmaceutical composition based on formula (I) compound.

EFFECT: obtained are novel dihydroquinone and dihydronaphthyridinone derivatives, useful for treatment of disease mediated by JNK kinase.

9 cl, 4 tbl, 38 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula , where A, Q, R1, R2, R3, R4, R5' are represented in i.1 of the formula, as well as to its hydrates, solvates and pharmaceutically acceptable salts, Also described are application of said compound and pharmaceutical composition, including such compound, for treatment of disease condition in mammals, which is sensitive to action of antagonists of vasopressin V1a, V1b or V2 receptors.

EFFECT: increase efficiency of compound application.

20 cl, 13 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula (I), its optical isomer or pharmaceutically acceptable salt, R is specified in cl.1 of the patent claim. The compounds may be presented both as an optical isomer, and as a racemic substance, and may be used for mental disorders, such as schizophrenia.

EFFECT: higher efficacy of using the compounds.

8 cl, 4 tbl, 3 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention offers compounds presented by general formula (I): or their pharmaceutically acceptable salts wherein R1, R2, R3 and R4 are presented in the description and exhibit substantial COMT inhobotory activity. Besides, the present invention described pharmaceutical compositions inhibiting catechol-O-transferase activity which contain the compound or its pharmaceutically acceptable salt as an active ingredient, and a pharmaceutically acceptable carrier.

EFFECT: there are declared pharmaceutical combinations for treatment or prevention of Parkinson's disease which contain (1) the pharmaceutical composition containing the compound under any cl 1-8 or its pharmaceutically acceptable salt and the pharmaceutically acceptable carrier, and (2) at least one compound specified in L-dope or carbidole.

10 cl, 9 ex, 17 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (VI): or its pharmaceutically acceptable salts; wherein n is equal to 0, 1, 2 or 3; R1 means -OH, H; R2a means OH, -CH3, provided at least one of R1 and R2a means -OH;R3 means Cl, Br, cyclopropyl, branched C3-5alkyl R4a means H; R8 means H; wherein the fragment: may be one of the groups B8, B35, B36, B37, B38, B39, B40, B41, B42, B43, B45, B46, B48, B54, B56, B58, B59, B61, B62, B71, B72, B74, B75, B76, B77, B78, B79, B80, B81, B82, B84, B86, B87, B88, B89, B90, B91, B93, B94, B95, B96, B97, B98, B99, B100 and B101 wherein the values are disclosed in the patent claim 1.

EFFECT: compounds show Hsp90 inhibitory activity that enables using them for treating the diseases caused by abnormal cell growth in mammals.

26 cl, 8 dwg, 2 tbl, 82 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyridine-3-yl derivatives of formula (I)

wherein A represents *-CONH-CH2-, *-CO-CH=CH-, *-CO-CH2CH2-, or wherein asterisks specify a link which binds with a pyridine group of formula (I); R1 represents hydrogen, C1-4alkyl or chlorine; R2 represents C1-5alkyl or C1-4alkoxy group; R4 represents hydrogen or C1-4alkyl; R4 represents hydrogen, C1-4alkyl; C1-4alkoxy group or halogen; R5 represents -CH2-(CH2)n- CONR51R52, -CO-NHR51, 1-(3-carboxyazetidinyl)-2-acetyl, hydroxy group, hydroxyC2-5alkoxy group, di-(hydroxy C1-4alkyl) C1-4alkoxy group, 2,3-dihydroxypropoxy group, 2-[(azetidine-3-carboxylic acid)-1-yl]ethoxy group, -OCH2-CH(OH)-CH2-NR51R52 or -OCH2-CH(OH)-CH2-NHCOR54; R51 represents hydrogen, C1-3alkyl, 2-hydroxyetyl, 2-hydroxy-1-hydroxymethyletyl or 2,3-dihydropropyl; R52 represents hydrogen; R54 represents hydroxymethyl; n represents 0 or 1; and R6 represents hydrogen, C1-4alkyl or halogen; and a salt of said compound. Also the invention describes a pharmaceutical composition for prevention or treatment of diseases or conditions associated with activated immune system, on the basis of the compound of formula I and application of said compounds for preparing said pharmaceutical composition.

EFFECT: there are produced and described new compounds which are especially active as immunomodulatory agents.

18 cl, 92 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formulae (I) and (III), as well as isomers or pharmaceutically acceptable salts thereof: where the values of radicals are given in claim 1 and 5. The invention also relates to a pharmaceutical composition based on said compounds, which has vanilloid receptor antagonist activity, use of said compounds to produce a medicinal agent for preventing or treating a condition which is associated with aberrant expression and/or aberrant activation of the vanilloid receptor. Described also is a method of producing a compound of formula III.

EFFECT: novel compounds which can be used as vanilloid receptor antagonists, for preventing or treating diseases are obtained and described.

40 cl, 281 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: present invention refers to new compounds of formula I-9 where q is represented by 1; R11 is represented by C3-8-alkyl; C3-8-cycloalkyl or C3-8-cycloalkyl-C1-3-alkyl; A is represented by phenyl substituted by one or more substituting groups independently chosen from R12; and R12 is represented by -(CH2)-NR13R14; R13 is represented by C1-6-alkylcarbanil; and R14 is represented by hydrogen; and to the pharmaceutically acceptable salts of such compounds and to the pharmaceutical compositions based on such compounds. It has been revealed that the compounds of formula I-9 are histamine NZ-receptor antagonists and thus that they can be used in treatment of diseases connected with expression of such receptors.

EFFECT: compounds of formula I-9 can be used in treatment of diseases connected with expression of histamine NZ-receptors.

6 cl, 216 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a method of producing 1,3-oxathiolane nucleosides, which involves reaction of (5-acetyloxy-1,3-oxathiolan-2-yl)methyl butanoate with a silylated pyrimidine or purine base in the presence of TiCl3(isopropoxide). Said reaction enables to obtain a product mainly containing β anomer.

EFFECT: efficient method of producing 1,3-oxathiolane nucleosides.

13 cl, 3 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of splitting a racemic mixture of cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane to obtain an optically active mixture of cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane, involving the following steps: a) dissolving and heating said racemic mixture of cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane in a solvent in the presence of (1R)-(-)-10-camphorsulphonic acid and achiral acid to form a solution containing the following two diastereoisomeric salts: (-)-cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane• (1R)-(-)-10- camphorsulphonate and (+)-cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane•(1R)-(-)-10- camphorsulphonate; b) cooling the solution to facilitate crystallisation of diastereomeric salts; c) extraction of crystals of the optically active mixture of said two diastereomeric salts obtained at step b), which contains excess (-)-cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane• (1R)-(-)-10- camphorsulphonate over (+)-cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane•(1R)-(-)-10- camphorsulphonate, and d) treating said optically active mixture of said two diastereomeric salts to remove (1R)-(-)-10- camphorsulphonic acid in order to obtain an optically active mixture of cis-2-hydroxymethyl-4-(cytosin-1'-yl)-1,3-oxathiolane.

EFFECT: improved method.

16 cl, 3 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which have formula (1a):

, where R1 represents hydrogen, (C1-C4)alkyl or halogen; R2 represents hydrogen, halogen, amino, (C1-C4)alkyl, heterocyclyl, (C6-C10)aryl-(C1-C4)alkylheterocyclyl, (C3-C6)cycloalkylheterocyclyl, -NR11R12, NHR16; R3 represent hydrogen, NR11R12 or NHR16; R4 and R5 each are independently selected from: hydrogen, halogen, (C1-C4)alkyl; R6 and R8 are each independently selected from: hydrogen, (C1-C4)alkyl or halogen; R7 is hydroxy-(C1-C4)alkyl, formyl, -(CH2)nC(O)OR10 or CONHR16; R10 is hydrogen, (C1-C4)alkyl; R11 and R12 each are independently selected from hydrogen, (C1-C4)alkyl, hydroxy-(C1-C4)alkyl, halogen-(C1-C4)alkyl, amino-(C1-C4)alkyl; or R11 and R12, together with N atom, to which they are bound, form 6- or 7-member heterocycle, optionally having one or more additional heteroatoms N or O; R16 is formyl, (C1-C4)alkyl, halogen-(C1-C4)alkyl, hydroxy-(C1-C4)alkyl, (C1-C4)alkylcarbonyl, halogen-(C1-C4)alkylcarbonyl, hydroxy-(C1-C4)alkylcarbonyl, (C1-C4)alkylcarbonyloxy-(C1-C4)alkylcarbonyl or heterocyclyl-(C1-C4)alkylcarbonyl; n is 0, 1 or 2; where (C1-C4)alkyl is not substituted or is substituted with two similar or different groups, selected from: halogen, hydroxy-group and (C6-C10)aryl; heterocyclyl represents 6- or 7-member saturated monocyclic ring, containing one or two heteroatoms selected from nitrogen and oxygen, and which is not substituted or is substituted with one or two similar or different groups, which are selected from oxogroup, (C1-C4)alkyl, (C3-C6)cycloalkyl, (C6-C10)aryl, hydroxy-(C1-C4)alkyl, (C6-C10)aryl-(C1-C4)alkyl, formyl, (C1-C4)alkylcarbonyl, (C6-C10)aryl-(C1-C4)alkylcarbonyl, (C6-C10)arylcarbonyl, (C3-C6)cycloalkylcarbonyl, -SH, -S-(C1-C4)alkyl and -S(O)2-(C1-C4)alkyl; (C6-C10)aryl is not substituted or is substituted with (C1-C4)alkyl; W represents S(O)m; m equals 0, 1 or 2; and to their pharmaceutically acceptable salts. Invention also relates to compounds of formula (1a'), to methods of obtaining compounds of formula (1a), to methods of obtaining compounds of formula (1a'), to method of obtaining compounds of formula E2, to pharmaceutical compositions, as well as to application of compounds.

EFFECT: obtaining novel biologically active compounds which demonstrate inhibiting effect with respect to activity of tumour necrosis factor-α.

30 cl, 46 ex, 4 tbl

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for preparing 1,3-oxathiolan nucleosides or a method for preparing derivatives of 1,3-oxathiolanyl-5-one that involve effective methods for formation of 1,3-oxathiolan ring followed by condensation of 1,3-oxathiolan with pyrimidine or purine base. Using indicated methods these compounds can be synthesized as separate enantiomers with high selectivity.

EFFECT: improved preparing methods.

27 cl, 3 dwg, 16 ex

The invention relates to a method of separating a mixture of enantiomers of CIS-2-hydroxymethyl-5-(5-fertilizin-1-yl)-1,3-oxathiolane: by passing through the associated with cyclodextrin chiral column; selective hydrolysis of 5’-O-acyl derivative of the nucleoside with the help of enzymes; selective deamination of a mixture of enantiomers using titidindezaminaza

The invention relates to 1-methyl-5-alkylsulfonyl-, 1-methyl-5-alkylsulfonyl - 1-methyl-5-alkylthiomethyl pyrazolylborate and herbicide tool based on them

The invention relates to a derivative of piperazine and piperidine derivatives of General formula (a) where And denotes a heterocyclic group with 5-7 atoms in the ring containing 1-2 heteroatoms from the group O, N and S; R1denotes hydrogen or fluorine; R2denotes oxoprop or1-4alkyl and p = 0 or 1; Z represents carbon or nitrogen, and the dotted line represents a simple bond when Z is nitrogen, and simple or double bond when Z is carbon; R3and R4independently of one another denote hydrogen or C1-4alkyl; n = 1 or 2; R5stands WITH1-4alkoxy, C1-4alkyl, halogen or hydroxy, and q = 0 or 1; Y represents phenyl, substituted by 1-2 substituents from the group of hydroxy, halogen, C1-4alkoxy, cyano, aminocarbonyl, di-C1-4alkylamino-carbonyl; furyl or thienyl and their salts

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-alkyl(aryl)-2,2'-bithiophene-5-carboxylic acids and esters thereof of general formula I where R = C1-C10-alkyl or aryl; R1 = hydrogen atom or C1-C4 alkyl, involving reaction of 2-acyl thiophenes of general formula II with dimethyl formamide and phosphoryl chloride, and the formed 2-alkyl(aryl)-3-chloro-3-(2-thienyl)acrylaldehyde of general formula III reacts with thioglycolic ester in the presence of a base, and by hydrolysis of the obtained esters of general formula I, where R assumes values given above and R1=C1-C4 alkyl, 3-alkyl-2,2'-bithiophene-5-carboxylic acids are obtained, where R1 = hydrogen atom.

EFFECT: simpler method of producing compounds of formula I, which can be used in synthesis of solvatochromic and thermochromic dendrimers, oligothiophenes with adjustable electrical and optical properties.

1 cl, 4 ex

Up!