Hepatitis c virus replication inhibitor

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and their pharmaceutically acceptable salts of formula (I) where n equals 0, 1 or 2, A is a five- or six-member aromatic ring which optionally contains one or two heteroatoms independently selected from nitrogen, oxygen or sulphur, B is a 5-9-member ring containing 0 or 1 double bonds and optionally contains an additional heteroatom selected from nitrogen and oxygen; where the ring optionally contains one or two substitutes independently selected from a group comprising C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkyl, carboxy, cyano, hydroxy, hydroxy-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, (NR4R5)-carbonyl or oxo; R1 is selected from -C(O)NR4R5 - CO2R4, 5-tetrazolyl, cyano; each R2 is independently selected from a group comprising C1-C6-alkyl, amino, benzyloxy, halogen, hydroxyl; R3 is a 5-7-member cycloalkyl ring; values of the rest of the radicals are given in the formula of invention. The invention also relates to a method for synthesis of the said compounds, a method of inhibiting HCV replicon function and a method of inhibiting functioning of the HCV NS5B protein.

EFFECT: wider field of use of the compounds.

16 cl, 4 tbl, 29 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where n is 0, 1 or 2,
Rather it represents a five - or six-membered aromatic ring, optionally containing one or two heteroatoms independently selected from nitrogen, oxygen or sulfur,
Represents a 5 to 9 membered ring containing 0 or 1 double bond, and optionally containing one additional heteroatom selected from and the PTA and oxygen;
moreover, the ring optionally has one or two substituent independently selected from the group comprising C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkyl, carboxy, cyano, hydroxy, hydroxy-C1-C6-alkyl, di-C1-C6-alkylamino-C1-C6-alkyl, (NR4R5)-carbonyl and oxo;
R1selected from -(C(O)NR4R5- CO2R4A 5-tetrazolyl, cyano,
each R2independently selected from the group comprising C1-C6-alkyl, amino, benzyloxy, halo, hydroxy;
R3is a 5-7-membered cycloalkyl ring;
R4selected from the group comprising hydrogen, C1-C6-alkyl, (di-C1-C6-alkylamino)-C1-C6-alkyl;
R5selected from the group comprising hydrogen, C1-C6-alkyl, hydroxy-C1-C6-alkyl, (di-C1-C6-alkylamino)-C1-C6-alkyl, phenyl, phenyl-C1-C6-alkyl, substituted by 2 substituents selected from C1-C6-alkoxy, hydroxy, (NR6R7)carbonyl, -S(O)2R8, -S(O)2NR6R7,
,,and
or NR4R5together they are pyrrolidinyl, piperidinyl, piperazinil. homopiperazine, morpholinyl, which is substituted by 1-2 substituents selected from the group consisting of C1-C6-alkyl, hydroxy, di-C1-C6-alkylamino, pyrrolidinyl and pyridinyl;
R6and R7independently selected from hydrogen and C1-is 6-alkyl;
R8selected from C1-C6-alkyl, C3-C7-cycloalkyl, phenyl and a five-membered heteroaryl containing 2 heteroatoms selected from nitrogen, with the specified heteroaryl contains one Deputy, is selected from C1-C6-alkyl;
R9and R10together with the carbon atom to which they are attached, form a 4-7-membered saturated ring, optionally containing 1 heteroatom selected from nitrogen;
R11represents C3-C7-cycloalkyl, phenyl, a five-membered saturated ring containing 1 heteroatom selected from nitrogen; a five - or six-membered aromatic ring containing 2 or 3 heteroatoms selected from nitrogen, oxygen and sulfur, and these rings optionally contain one Deputy, is selected from C1-C6-alkoxycarbonyl-C2-C6-alkenyl, phenyl, carboxy-C2-C6-alkenyl, carboxy-C1-C6-alkyl and five-membered aromatic ring containing 2 heteroatoms selected from nitrogen and sulfur, and phenyl and heteroaryl substituted by one Deputy, is independently selected from C1-C6-alkoxycarbonyl-C2-C7-alkenyl, carboxy, carboxy-C2-C6-alkenyl, carboxyethyl and hydroxy,
or its pharmaceutically acceptable salt.

2. The compound according to claim 1, where a represents a furyl, phenyl or pyridinyl.

3. The compound according to claim 1, where In is a 5-9-membered ring containing 0 or 1 double bond, and optionally containing od the n additional heteroatom, selected from nitrogen and oxygen, and the ring optionally has one or two substituent independently selected from C1-C6-alkoxy, C1-C6-alkoxycarbonyl, carboxy, hydroxy, (NR4R5)-carbonyl and oxo.

4. The compound according to claim 1, where In is semiline ring containing 0 or 1 double bond, and optionally containing one additional heteroatom selected from nitrogen and oxygen, and the ring optionally has one or two substituent independently selected from C1-C6-alkoxy, C1-C6-alkoxycarbonyl, carboxy, hydroxy, (NR4R5)-carbonyl and oxo.

5. The compound according to claim 4, where R4selected from the group comprising C1-C6-alkyl, (di-C1-C6-alkylamino)-C1-C6-alkyl, R5selected from the group comprising hydrogen, C1-C6-alkyl, hydroxy-C1-C6-alkyl, (di-C1-C6-alkylamino)-C1-C6-alkyl, (NR6R7)-carbonyl, -S(O)2R8, S(O)2NR6R7or NR4R5together they are pyrrolidinyl, piperidinyl, piperazinil, homopiperazine, morpholinyl, which is substituted by 1-2 substituents selected from the group consisting of C1-C6-alkyl, hydroxy, di-C1-C6-alkylamino, pyrrolidinyl and pyridinyl.

6. The compound according to claim 1, where R1selected from-C(O)NR4R5and-CO2R4.

7. The compound according to claim 1, where R1represents-C(O)NR4R5, R4is vodor the house, and R5represents-S(O)2R8or-S(O)2NR6R7.

8. The compound according to claim 1, in which R1is-C(O)NR4R5, R4is hydrogen, R5is
selected from the group consisting of
,,,,,,,,,.

9. The compound according to claim 1, where each R2independently selected from halo and hydroxy.

10. The compound according to claim 1, where n is 0 or n is 1, a R2is a halo.

11. The compound according to claim 1 of formula (II)
or its pharmaceutically acceptable salt, where
And selected from Furie, phenyl or pyridinyl,
Represents a 5 to 9 membered ring containing 0 or 1 double bond, and optionally containing one additional heteroatom selected from nitrogen and oxygen, and the ring optionally has one or two substituent independently selected from the group comprising Cl-C6-alkoxy, C1-C6-alkoxycarbonyl, carboxy, hydroxy, (NR4R5)-carbonyl and oxo;
R1selected from-C(O)NR4R5and-CO2Rsup> 4;
R2selected from benzyloxy, hydroxy;
R4selected from the group comprising hydrogen, C1-C6-alkyl, (di-C1-C6-alkylamino)-C1-C6-alkyl;
R5selected from the group comprising hydrogen, C1-C6-alkyl, hydroxy-C1-C6-alkyl, (di-C1-C6-alkylamino)-C1-C6-alkyl, -S(O)2R8, -S(O)2R6R7,and
or NR4R5together they are pyrrolidinyl, piperidinyl, piperazinil, homopiperazine, morpholinyl, which is substituted by 1-2 substituents selected from the group consisting of C1-C6-alkyl, hydroxy, di-C1-C6-alkylamino, pyrrolidinyl and pyridinyl;
R6and R7independently selected from hydrogen and C1-C6-alkyl;
R8selected from C3-C7-cycloalkyl, phenyl and a five-membered heteroaryl containing 2 heteroatoms selected from nitrogen, with the specified heteroaryl contains one Deputy, is selected from C1-C6-alkyl;
R9and R10together with the carbon atom to which they are attached, form a 4-7-membered saturated ring, optionally containing 1 heteroatom selected from nitrogen; and
R11represents phenyl, five - or six-membered aromatic ring containing 2 or 3 heteroatoms selected from nitrogen, oxygen and sulfur, and these rings optionally contain one Deputy, is selected from C1-C6-alkoxycarbonyl-C2-C6-Ala the Nile, phenyl, carboxy-C2-C6-alkenyl and carboxy-C1-C6-alkyl, and phenyl and heteroaryl substituted by one Deputy, is independently selected from carboxy, carboxy-C2-C6-alkenyl.

12. The compound according to claim 1, selected from the group consisting of
;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; ;;;;;;;;;;;;;;;;;;and.

13. The compound according to claim 1, selected from the group consisting of
;;;;;
;;;
;;;;;
;;;;;
;;;;;and
or what about the pharmaceutically acceptable salt.

14. The method of obtaining

where Rarepresents C1-C6-alkyl, a R2absent or represents C1-C6-alkoxy or halo, including interaction


under alkaline conditions in aprotonin solvent.

15. A method of inhibiting the function of the HCV replicon comprising contacting the HCV replicon with a compound of formula I or its pharmaceutically acceptable salt.

16. A method of inhibiting the function of the HCV NS5B protein, comprising contacting the HCV NS5B protein with the compound of the formula I or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (1a), formula (1b), formula (1c) and formula (1d), as well as pharmaceutical composition based on them and their application in medicine obtainment. R1-R4, G, W, X, X1, U, V, a, b are defined in the invention claim.

EFFECT: compound with antagonistic effect on vasopressin V1A receptor.

73 cl, 133 ex

Quinolone analogues // 2349586

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula (1): and to their pharmaceutical salts, where B, X, A or V are not present, if Z1, Z2, Z3 or Z4 respectively represent N, and independently H, halogen atom, azido, R2, CH2R2, SR2, OR2 or NR1R2, when Z1, Z2, Z3 or Z4 represent C. In each NR1R2, R1 and R2 together with N there can be formation of an optionally substituted piperidine, pyrrolidine, piperazine or morpholine ring. Z1 represents N and Z2, Z3 and Z4 represent C, or Z1 and Z3 represent N and Z2 and Z4 represent C. W together with N and Z form an optionally substituted thiazole, imidazole or pyrimidine ring, which is condensed with an optionally substituted ring, chosen from a group consisting of: or . U represents NR1R2, NR1-(CR12)n-NR3R4, where in NR3R4, R3 and R4 together with N there can be formation of an optionally substituted piperidine, pyrrolidine, piperazine or morpholine ring. R1 and R3 independently represent H or C1-6alkyl. Each R2 represents H or C1-10alkyl, each optionally substituted with a halogen atom, or C3-6cycloalkyl, aryl, heteroaryl or pyridine, pyrrolidine, piperazine or morpholine ring, where each ring is optionally substituted; or R2 is optionally substituted with piperidine, pyrrolidine, pyridine, piperazine, pyrazine, morpholine or benzimidazole. R2 represents H or C1-10alkyl. Each R5 represents a substitute in any position in ring W, and is H, OR2, amino, alkoxy, amido, halogen atom or cyano; or R5 represents C1-6alkyl, -CONHR1-, each optionally substituted with a halogen atom; or two adjacent R5 are linked with formation of a 5-6-member ring, an optionally substituted heterocyclic ring, chosen piperidine, pyrrolidine, piperazine or morpholine ring. n equals 1-6, and each optionally substituted part can be substituted with one or more halogens, OR2, NR1R2 , carbamate, C1-10alkyl, each optionally substituted with a halogen atom, C=O, cyano, nitro, COR2, NR2COR2, sulphonyl amides, NR2SOOR2; SR2, SOR2, COOR2, CONR22, OCOR2, OCOOR2 or OCONR22. The invention also relates to pharmaceutical compositions, to the method of suppressing proliferation of cells and/or weakening cell proliferative breakdown, to the method of reducing microbe titre and/or weakening microbe infection, to the method of inducing death of cells and/or inducing apoptosis, to compounds, chosen from a group, to pharmaceutical compositions, as well as to the method of producing compounds with formula (1).

EFFECT: obtaining new biologically active compounds, which can suppress proliferation of cells and/or induce apoptosis.

41 cl, 113 ex, 12 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using phenylethenyl- or phenylethynyl-derivatives as antagonists of glutamates receptors. Invention describes using compound of the general formula (I):

wherein each among R1, R2, R3, R4 and R5 means independently of one another hydrogen atom, (C1-C6)-alkyl, -(CH2)n-halogen, (C1-C6)-alkoxy-group, -(CH2)n-NRR', -(CH2)n-N(R)-C(O)-C1-C6)-alkyl, phenyl or pyrrolyl that can be unsubstituted or substituted with one or more (C1-C6)-alkyl; each among R, R' and R'' means independently of one another hydrogen atom or (C1-C6)-alkyl; A means -CH=CH- or C≡C; B means ,, , , or wherein R6 means hydrogen atom, (C1-C)-alkyl, -(CH2)n-C(O)OR, or halogen atom; R7 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-C(O)OR', halogen atom, nitro-group or oxodiazolyl group that can be unsubstituted or substituted with (C1-C6)-alkyl or cycloalkyl; R8 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-OH, -(CH2)n-C(O)OR'' or phenyl; R9 means (C1-C6)-alkyl; R10 and R11 mean hydrogen atom; R12 means -(CH2)n-N(R)-C(O)-(C1-C6)-alkyl; R13 means hydrogen atom; each R14, R15, R16 and R17 independently of one another means hydrogen atom or (C1-C6)-alkoxy-group; each R18, R19 and R20 independently of one another means hydrogen atom; R21 means hydrogen atom or (C1-C6)-alkyl; R22 means hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkyl comprising one or more substitutes chosen from groups hydroxy- or halogen atom; R23 means hydrogen atom, (C1-C6)-alkanoyl or nitro-group; each among R24, R25 and R26 independently of one another means hydrogen atom or (C1-C6)-alkyl; n = 0, 1, 2, 3, 4, 5 or 6; X means -O- or -S-; Y means -CH= or -N=, and its pharmaceutically acceptable salts used in preparing medicinal agents designates for treatment or prophylaxis of disorders mediated by mGluR5-receptors. Also, invention describes compounds of the formula (I-A), compound of the formula (I-B-1) given in the invention description, and a medicinal agent used in treatment or prophylaxis of disorders mediated by mGluR5-receptors.

EFFECT: valuable medicinal properties of compounds.

44 cl, 1 tbl, 44 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel heterocyclic compounds comprising 2-aminopyridin-3-sulfonic fragment of the general formula (1) or their pharmaceutically acceptable salts, N-oxides or hydrates possessing properties of antagonists of glutamate-induced calcium ions transport, in particular, neuroprotective effect. Also, invention relates to the focused library for the search of biologically active leader-compounds comprising at least one heterocyclic compound of the general formula (1) and to pharmaceutical composition if form of tablets, capsules or injections placed into pharmaceutically acceptable package containing compounds of invention as an active substance. In compound of the general formula (1) R1 represents hydrogen atom; R2 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; or R1 and R2 in common with nitrogen and sulfur atoms to which they are bound form optionally substituted and optionally condensed with other cycles 1,1-dioxo-4H-pyrido[2,3-e][1,2,4]thiadiazine or optionally substituted and optionally condensed with other cycles 5,5-dioxo-5,6,7,9-tetrahydro-5-thia-1,6,9-triazabenzocyclohepten-8-one. Also, invention discloses methods for preparing different compounds of the general formula (1).

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

10 cl, 4 sch, 4 tbl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

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

20 cl, 6 tbl, 192 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to oxazolo- and thiazolo-[4,5-c]-quinoline-4-amines of the general formula (I)

wherein R1 is taken among group consisting of oxygen and sulfur atoms; R2 is taken among hydrogen atom, alkyl, alkyl-OH (hydroxyalkyl), alkyl-X-alkyl, alkyl-O-C(O)-N(R5)2, morpholinyl, pyrrolidinyl, alkyl-X-aryl radical, alkenyl-X-aryl radical; each substitute R3 and R4 represents hydrogen atom or substitutes R3 and R4 taken in common form the condensed aromatic or [1,5]-naphthiridine system; X represents -O- or a single bond; R5 represents hydrogen atom. Also, invention describes intermediate compounds, pharmaceutical composition and a method for stimulating biosynthesis of cytokinins (cytokines) based on these compounds. Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable properties of compounds.

21 cl, 2 tbl, 64 ex

The invention relates to organic chemistry and can find application in medicine

The invention relates to an improved process for the preparation of 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-f] xanthine of the formula I, causing the induction of microsomal liver enzymes

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (1a), formula (1b), formula (1c) and formula (1d), as well as pharmaceutical composition based on them and their application in medicine obtainment. R1-R4, G, W, X, X1, U, V, a, b are defined in the invention claim.

EFFECT: compound with antagonistic effect on vasopressin V1A receptor.

73 cl, 133 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to D-proline derivatives of formula I or IA wherein R1 and R2 are independently lower alcoxy, lower alkenyloxy, hydroxy, -OCH(CH3)OC(O)-lower alkyl or -OCH2C(O)N(R3)N(R4), with the proviso, that only one from R1 and R2 represent hydroxy; R3 and R4 are independently hydrogen, lower alkyl? Lower alkenyl, or cycloalkyl; or R1 and R2 together with carbon atom to which they are attached form linkage group X, wherein X represents -O(CH2)nCH=CH(CH2)nO- or -O(CH2)mO-; n = 1, 2 or 3; m = 4-8.

EFFECT: new prodrugs.

14 cl, 1 tbl, 25(29) ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to derivatives of general formula I , wherein R1, R2 and R3 are independently H or C1-C4-alkyl; Ar is condensed thiophene or pyridine ring optionally substituted with one or more substituents selected from C1-C4-alkyl, C1-C4-alkyloxy, C1-C4-alkyloxy(C1-C4)-alkyl, CF3, halogen, nitro, cyano, NR4R5 NR4COR6 and CONR4R5 (R4 and R5 are independently H or C1-C4-alkyl; or R4 and R5 together with adjacent nitrogen atom form 5- or 6-membered saturated heterocyclic ring; R6 is C1-C4-alkyl): A is residue of 4-7-membered saturated heterocyclic ring optionally containing nictogen atom and optiomally substituted with 1-3 substituents selected from C1-C4-alkyl, C1-C4-alkyloxy, hydroxyl, halogen, and alkoxy; and pharmaceutical composition based on the same; with the proviso, that compound of formula I wherein A represents condensed [3,2-f]pyridine ring; each R1, R2 and R3 represents H, and A represents (CH2)3. Also described are application of abovementioned derivatives, pharmaceutical composition enhancing of synaptic response mediated with AMPA receptors in CNS based on the same, and method for treatment of neurological diseases or mental disorders.

EFFECT: new compounds with value biological properties.

7 cl, 1 tbl, 12 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates in particular to derivatives of acylbenzoxazine of the formula: wherein radicals X1 and X2 are taken independently among hydrogen atom, -OR3, -CH2OR3, or taken in common they represent -OCR

42
O-, -OC2R44
O-, -OC2R42
O- wherein in each case R in residue (CR2) represents hydrogen atom, oxy-group, (C1-C6)-alkoxy; R3 represents hydrogen atom, (C1-C6)-alkyl; in each case radical R1 represents hydrogen atom or (C1-C6)-alkyl; in each case radical R4 represents hydrogen atom or (C1-C6)-alkyl; n = 1, 2, 3 or 4. Compounds elicit the higher effect as compared with corresponding benzoylpiperidines for enhancing the synaptic responses mediated by AMPA-receptors. Also, invention relates to methods for their using for treatment of patients suffering with disorders in nervous and intellectual activity as result of insufficiency in function of some excitement synapses or in some AMPA-receptors. Compounds of the present invention can be used for treatment of patients without indicated disorders for enhancing activity associated with sensomotor and cognitive tasks that depend on the brain reticular structure using AMPA-receptors and for improving the memory encoding.

EFFECT: valuable biological and medicinal properties of compounds.

13 cl, 1 tbl, 5 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new biologically active benzoxazine compounds and describes derivatives of benzoxazine of the following structure: wherein X1 and X2 are taken independently among hydrogen atom (H), -OR4, -CH2OR4; or X1 and X2 taken in common represent -O-CR

52
O- or -O-CR52
CR52
O-, or -O-CR52
=CR52
O-; Z represents oxygen atom (O) or sulfur atom (S); each R1 represents independently hydrogen atom (H) or (C1-C6)-alkyl; each R2 represents independently hydrogen atom (H) or (C1-C6)-alkyl, (C1-C3)-fluoroalkyl; each R4 represents independently hydrogen atom (H) or (C1-C6)-alkyl; each R5 represents hydrogen atom (H) or (C1-C6)-alkyl; n = 2, 3 or 4. Also, invention describes a method for preparing compound by cl. 1 with enantiomeric excess above 80% and relates to pharmaceutical composition for enhancing the synaptic response mediated by AMPA-receptors based on compounds by cl. 1. Pharmaceutical composition is useful for treatment of schizophrenia, schizophrenia-like behavior or depression in humans in necessary for carrying out such treatment based on compounds by cl. 1 wherein this pharmaceutical composition is useful for the memory improvement and comprising compound by cl. 1. Invention provides preparing new compounds eliciting useful biological properties.

EFFECT: valuable medicinal properties of compounds.

107 cl, 2 dwg, 2 tbl, 10 ex

--carboline" target="_blank">

The invention relates to bellrowan-carbolines, formula I, where R3denotes-CO-R1or group (a); R1- C1-C6alkoxy; R2- N2C1-C4alkyl, C1-C4alkoxy - C1-C2alkyl; And -- 5-6-membered unsaturated cycle, in which 1-2 carbon atoms may be replaced by N, O and/or S, which may be substituted with one R5or R6; R5and R6identical or different, denote H, C1-C6alkyl, NR7R8C1-C6alkyl which may be substituted by hydroxyl or C1-C4alkoxyl, phenyl, 5-6-membered heteroaryl residue, which contains one or two atoms of N, O or S, and phenyl and heteroaryl residue may be substituted C1-C4the alkyl, C1-C4alkoxyl, halogen, or R5and R6together,- CH2)nwhere n = 4; R7and R8- H, C1-C4alkyl, acyl, as well as their isomers, tautomers and salts

-lactams" target="_blank">

-lactams // 2143435
The invention relates to new derivatives-lactam of General formula I given in the description, in which Z denotes a methylene, oxygen or sulfur and R represents hydrogen, optionally substituted, lower alkoxycarbonyl, carbamoyl, lower (cyclo)allylcarbamate, phenylcarbamoyl or hydroxyphenylarsonic lower alkyl, lower alkenylacyl, formyl, optionally substituted with halogen, CYANOGEN, carbarnoyl-lowest alkylthiol, lower alkanoyl, respectively alkylsulfonyl, optionally substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxycarbonyl lower alkyl or carboxy-lower alkyl carbarnoyl or ring structure of a General formula

Q-X-CO- (A1),

Q-X-SO2(A2),

where is a five - or six-digit, optionally containing nitrogen, sulfur and/or oxygen ring;

X denotes one of the groups-CH2, -CH2CH2-, -NH-, NHCH2-, -CH2NH-, -CH(NH2)--CH2CH2NH-, -C(=NOCH3)-, -OCH2-, -SCH2-;

A represents lower alkyl, hydroxy-(lower alkyl, vinyl, cianfrini, lower alkoxy, optionally phenylselenenyl lower alkylsulfonate, the remainder is-S-Het or-S- 2-L, where L is a lower alkanoyloxy, respectively carbamoylated, low-alkoxycarbonyl, carboxy, azido, lower alkanolamine, lower alkylsulfonyl, six-membered ring attached to the nitrogen atom, or a residue - or-S-CH2-Het, where Het has the above significance,

and pharmaceutically acceptable, readily hydrolyzable esters and salts of these compounds

FIELD: chemistry.

SUBSTANCE: invention relates to novel 3,11b-cys-dihydrotetrabenazene of general formula (1) or to its antipode . Invention also relates to composition, to pharmaceutical composition, to application of 3,11b-cys-dihydrotetrabenazene, to method of obtaining 3,11b-cys-dihydrotetrabenazene by i. 1, to compounds of formula (II), (III), as well as to ester of Mosher's acid and 3,11b-cys-dihydrotetrabenazene.

EFFECT: obtaining novel biologically active compounds possessing activity as inhibitor of vesicular carrier of monoamines VMAT2.

23 cl, 12 ex, 8 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: new annelated asaheterocycles include pyrimidine fragment of general formula I in the form of free bases or pharmaceutically acceptable salts. Compounds of this invention possess properties of PI3 kinase inhibitors. In general formula I X represents oxygen atom or sulphur atom; Z represents oxygen atom, R1 represents hydrogen atom or optionally substituted C1-C6alkyl, or Z represents nitrogen atom together with bound carbon atom forming through Z and R1 optionally substituted annelated imidazoline cycle; R2 represents optionally substituted C1-C6alkyl, optionally substituted C3-C8cycloalkyl, optionally substituted phenyl, possibly annelated with 5-6-term heterocyclyl containing heteroatoms chosen from oxygen and nitrogen, optionally substituted 5-6-term heterocyclyl containing heteroatoms chosen from nitrogen, oxygen and/or sulphur, possibly annelated with phenyl ring. Invention also concerns method of production of compounds, pharmaceutical compositions and medical products.

EFFECT: effective application for preparation of medical products for oncologic therapy.

14 cl, 3 dwg, 1 tbl, 4 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel polycyclic compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7, cycle A, cycles B, X, Y and Z have values given in the invention claims and in description of the claim, and to their pharmaceutically acceptable salts also. Proposed compound possess an antitumor activity and can be used in treatment of oncological diseases. Also, invention relates to a pharmaceutical composition based on these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

23 cl, 1 tbl, 57 ex

FIELD: organic synthesis.

SUBSTANCE: invention relates to synthesis of camptotecin analogues from 2'-amino-5'-hydroxypropiophnone corresponding to AB ring portion of camptotecin structure and tricyclic ketone converted into CDE ring portion in camptotecin structure. Preparation of 2'-amino-5'-hydroxypropiophnone comprises following steps: (1) preparing compound (b) by mixing compound (a), benzylation agent, and a base followed by stirring mixture obtained in solvent on heating under reflux; (2) preparing compound (c) by dropwise adding Grignard reagent to compound (b) under an inert gas atmosphere; (3) preparing compound (d) by mixing compound (c) with an oxidant and stirring resulting mixture; and (4) preparing compound (e) via catalytic reduction of compound (d) (see scheme 1 below). Intermediate compounds (c') and (d') are described. Also described is a method for preparing tricyclic ketone to provide efficient complete synthesis of camptotecin serving as starting compound for irinotecan hydrochloride and a various types of camptotecin derivatives as well as for stable preparation of camptotecin and its derivatives. Scheme 1: .

EFFECT: expanded synthetic possibilities in camptotecin derivatives series.

5 cl, 17 tbl, 33 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to triheterocyclic compound of the formula (I): wherein X represents carbon atom; Y represents carbon or nitrogen atom; W represents carbon or nitrogen atom; U represents -CR2, and Z represents -CR2 or nitrogen atom; ring A represents (C5-C6)-cycloalkyl ring or 5-membered heterocyclic ring comprising one nitrogen, oxygen or sulfur atom; R1 represents alkyl, alkenyl, alkynyl, -NR4R5, -OR6 and others; R3 represents phenyl ring substituted with 1-3 substitutes or pyridyl or 1,3-dioxoindanyl ring substituted with 1-2 substitutes, and its pharmaceutically acceptable salts and pharmaceutical composition containing thereof as an active component. Also, invention relates to derivatives of pyrazolopyrimidine and derivatives of pyrrolopyrimidine. Compounds of the formula (I) show antagonistic activity with respect to corticotropin-releasing factor receptors. The compound can be used in treatment and/or prophylaxis of depression, anxiety state, disorders in food intake, post-traumatic stress, ulcerous disease, irritable bowel syndrome, Alzheimer's disease, abuse in drugs using or alcoholic syndrome dependence.

EFFECT: valuable medicinal properties of compounds and pharmaceutical agent.

7 cl, 1 dwg, 24 ex

Up!