2,4-di(aminophenyl)pyrimidines as plk-kinase inhibitors

FIELD: medicine.

SUBSTANCE: invention refers to new compounds exhibiting antiproliferative activity of formula (1) where W means N or C-R2; X means -NH-; Y means CH; Z means halogen, -NO2, C2-C3alkynyl-, halogen-C1-C3alkyl- and -C(=O)-C1-C3alkyl, A means a group of formula (i), (ii) or (iii) Q1 means phenyl; B1, B2, B3 and B4 independently mean C-RgRh, N-Ri or O; R1 means hydrogen; R2 means a residue specified from the group including hydrogen, halogen and -OR4; Ra, Rb, Rc, Rd, Re and Rf independently mean hydrogen; Rg and Rh independently mean a residue specified from the group including hydrogen, =O, -OR4 and -NR4C(=O)R5; or mean optionally a residue monosubstituted or twice-substituted with equal or different substitutes and specified from the group including C1-C6alkyl and phenyl, the substitute/substitutes is/are specified from the group including R8/, -OR4, -C(=O)R4, -C(=O)OR4 and -C(=O)NR4R5 where R8/ and other values of radicals are specified in the patent claim, optionally in the form of their pharmacologically noncontaminating acid addition salts. The invention also concerns a pharmaceutical composition.

EFFECT: new compounds have effective biological properties.

8 cl, 6 dwg, 1086 ex

 

The text descriptions are given in facsimile form.

1. Compounds of General formula (1)

where W represents N or C-R2;
X represents-NH-;
Y denotes CH;
Z denotes halogen, -NO2With2-C3quinil-, halogen-C1-C3alkyl - and
-C(=O)-C1-C3alkyl,
But denotes a group of the formula (i), (ii) or (iii)
,or,
Q1denotes phenyl;
In1In2In3and4independently of one another denote C-RgRhN-Rior;
R1denotes hydrogen;
R2denotes a residue selected from the group comprising hydrogen, halogen and
-OR4;
Ra, Rb , Rc, Rd, Reand Rfindependently of one another denote hydrogen;
Rgand Rhindependently of one another denote a residue selected from the group comprising hydrogen, =O, -OR4and-NR4C(=O)R5;
or indicate optional one-deputizing or dvuhkamernyi identical or different substituents residue selected from the group comprising C1-C6alkyl and phenyl, with the Deputy/deputies chosen/selected from the group comprising R8i, -OR4, -C(=O)R4, -C(=O)OR4and-C(=O)NR4R5where R8iselected from optionally substituted C1-C8of alkyl, C3-C10cycloalkyl, phenyl and 5-6-membered heteroaromatic residue containing one or two N atom in the cycle, and which may be condensed with a benzene ring, and Deputy/deputies may be the same or different and selected/selected from the group comprising halogen, -HE and-CN;
moreover, the residues Rgand Rhoptional, can form a saturated or partially unsaturated 3-to 5-membered alkyl bridge, attached to the adjacent C - or N-atom of one of the values In1In4with education artecontemporanea ring, or Rgand RhGeneral C-atom may form a 3-to 5-membered alkyl bridge, with the formation of pyrocondensation the frame ring;
Ridenotes a residue selected from the group comprising hydrogen and
-NR4C(=O)R5or denotes optional one-deputizing or mnogozalny identical or different substituents residue selected from the group comprising C1-C6alkyl, C2-C6quinil,3-C6cycloalkyl, phenyl, heterocyclyl, which represents a 5-6-membered saturated heterocyclic residue containing one or two heteroatoms selected from O and N, with the Deputy/deputies may be the same or different and selected/selected from the group comprising halogen, R8i, -OR4, -C(=O)NR4R5,
-NR4R5, -NR4C(=O)R5and-CN, where R8iselected from the group comprising hydrogen, C3-C6cycloalkyl, phenyl and heterocyclyl, which represents a 5-6-membered saturated heterocyclic residue containing one or two heteroatoms selected from O and N;
and Rgand Rioptional, can form a saturated or partially unsaturated 3-to 5-membered alkyl bridge, attached to the adjacent C - or
N-atom of one of the values In1In4with education artecontemporanea ring;
R3selected from groups of the formulas (iv), (v), (vii) and (x)

br/> R4and R5independently of one another denote hydrogen or a residue selected from the group including optional one-deputizing or dvuhkamernyi identical or different substituents From1-C5alkyl, C2-C5quinil,3-C10cycloalkyl and heterocyclyl representing, 5-6-membered saturated heterocyclic residue containing one or two heteroatoms N, the Deputy/deputies chosen/selected from the group comprising heterocyclyl, which represents a 5-6-membered saturated heterocyclic residue containing one or two heteroatoms selected from O, N, OR8, -NR8R9and-CN;
L represents a bond or a residue selected from the group including optional one-deputizing or mnogozalny identical or different substituents C1-C16alkyl, C3-C10cycloalkyl, phenyl, heterocyclyl, which represents a 5-6-membered saturated heterocyclic residue containing one or two heteroatoms N, the Deputy/deputies chosen/selected from the group comprising-OR8;
Q2and Q3independently of one another denote a bond or a residue selected from the group including optional one-deputizing or mnogozalny identical or different substituents From1-C16alkyl, C2 -C16alkenyl,2-C16quinil,3-C10cycloalkyl, phenyl, heterocyclyl, which represents a 5-6-membered saturated heterocyclic residue containing one or two heteroatoms N, and heteroaryl, which represents a 5-6-membered heteroaromatic residue, which contains two or three heteroatoms, selected from O and N, with the Deputy/deputies chosen/selected from the group comprising halogen, -OR8, -NR8R9and-CN;
and at least one Deputy, selected from the group L, Q2and Q3may not mean the connection;
R7denotes hydrogen or a residue selected from the group including optional one-deputizing or mnogozalny identical or different substituents C1-C16alkyl, C3-C10cycloalkyl, phenyl and heterocyclyl, which represents a 5-6-membered saturated heterocyclic residue containing one or two heteroatoms selected from O and N;
R8and R9independently of one another denote hydrogen or a residue selected from the group comprising optionally substituted C1-C8alkyl and C3-C10cycloalkyl, the Deputy, respectively, substituents which may be the same or different, selected/selected from the group comprising dimethylaminopropyl and diethylaminopropyl;
it is interesting in the form of their pharmacologically harmless acid additive salts.

2. Compounds of General formula (1) according to claim 1, in which W denotes C-R2and the remaining residues have the above values.

3. Compounds according to claim 1 or 2, in which
R3denotes a group of formula (iv) or (x)

and the remaining residues have the above values.

4. Compounds according to claim 1 or 2, in which Z denotes CF3and the remaining residues have the above values.

5. Compounds according to claim 1 or 2, or their pharmaceutically active salts, possessing inhibitory activity against PLK kinase, as an active ingredient for medicines.

6. Compounds according to claim 1 or 2, or their pharmaceutically active salts for the preparation of drugs with antiproliferative activity.

7. Compounds according to claim 1 or 2, or their pharmaceutically active salts for the preparation of drugs with antiproliferative activity with a mechanism of inhibitory effect on PLK kinase.

8. Pharmaceutical composition having anti-proliferative activity, containing as active substance one or more compounds of General formula (1) according to one of claims 1 or 2, or one or more of their physiologically compatible salts, optionally in combination with conventional excipients and/or carriers.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel compounds of formula (I), where R1 represents hydroxymethyl; R2 is selected from -C(O)NR4R5; HET-1 represents 5- or 6-member heteroaryl ring, bound by atom C; R3 represents halogeno; R4 and R5 together with nitrogen atom, to which they are bound, can form heterocyclyl ring system, as it is defined for HET-3; HET-3 represents possibly substituted azetidinyl; m equals 1; n equals 0, 1 or 2; or their pharmaceutically acceptable salt, which can be applied as glucokinase (GLK) activators or active ingredient of pharmaceutical compositions, also described are methods of obtaining them.

EFFECT: creation of novel compounds applied as glucokinase (GLK) activators in treatment of diabetes.

13 cl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: in embodiments of the invention, specific compounds are used to prepare a medicinal agent for treating, relieving and preventing conditions associated with dysfunction of monoamine transmission. The compounds have general formula (1) , where: R1 and R2 are identical or different and denote hydrogen, alkyl, alkenyl, alkynyl, aryl, thio or alkylthio, or R1 and R2 may have extra substitutes which are selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkyloxy, morpholin-4-ylalkoxy, piperidin-1-ylalkyloxy, alkylamino, dialkylamino, arylamino.

EFFECT: more efficient use of compounds in preparing medicinal agents.

8 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel 5-6-member nitrogen-containing heterocyclic compounds, selected form derivatives of pyridine, pyrimidine, imidasoline, oxadiasoline, such as, for instance , which possess inhibiting activity with respect to aspartylprotease, such as "ВАСЕ-1".

EFFECT: obtaining pharmaceutical composition, method of aspartylprotease inhibition aimed at application of compounds for preparation of medication intended for treatment of state, mediated by aspartylprotease, such as "ВАСЕ-1".

4 cl, 1 tbl, 1832 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives having FAK inhibitory activity of formula (I), where R0 is hydrogen; R1 is a 5- or 6-member heterocycle containing 1 or 2 nitrogen atoms substituted with (C1-C7)alkyl, hydroxyl group, dialkylamino group or a 6-member heterocycle containing one nitrogen atom; R2 is hydrogen; R3 is carbamoyl substituted once or twice with (C1-C7)alkyl; a 5-member heterocycle containing 4 nitrogen atoms; SO2N(R12)R13, where R12 is hydrogen or (lower)alkyl, and R13 is hydrogen, (C1-C7)alkyl, (C1-C7)alkoxy(C1-C7)alkyl, di(C1-C7)alkylamino(C1-C7)alkyl, hydroxy(C1-C7)alkyl, or R12 and R13 together a nitrogen atom with which they are bonded form a 6-member heterocycle containing two nitrogen atoms, where the said heterocycle is not substituted or substituted with (C1-C7)alkyl; R4 is hydrogen; R5 is a halide; R6 is hydrogen; R7 is hydrogen; (C1-C7)alkoxy; carbamoyl which is not substituted or substituted with (lower)alkyl; a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with di(C1-C7)alkylamino, (C1-C7)alkyl, hydroxy, 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms, unsubstituted or substituted with (C1-C7)alkyl; 6-member heterocycle-oxy containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen ring atoms which is not substituted or substituted with (C1-C7)alkyl; R8 is hydrogen; halide; (C1-C7)alkoxy, carbamoyl unsubstituted or substituted with (C1-C7)alkyl; heterocycle(C1-C7)alkyloxy, where heterocycle denotes a 5-member heterocycle containing 1 nitrogen ring atom, unsubstituted or substituted with (C1-C7)alkyl; 5- or 6-member heterocycle containing 1 or 2 nitrogen or oxygen atoms, unsubstituted or substituted with one or two substitutes independently selected from hydroxy, (C1-C7)alkyl, aminocarbonyl and (C1-C7)alkylamino; 6-member heterocycle-oxy, containing 1 nitrogen ring atom, unsubstituted or substituted 1-5 times with (C1-C7)alkyl or di(C1-C7)alkylamino; or R7 and R8 together with atoms with which they are bonded form a 6-member heterocycle containing two nitrogen or oxygen atoms, unsubstituted or substituted once or twice with (C1-C7)alkyl or oxo group; R9 is hydrogen; R10 is (C1-C7)alkoxy, as well as to their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition and synthesis method.

EFFECT: novel compounds have useful biological activity.

4 cl, 167 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry, and specifically to compounds of general formula I , where A is an oxygen atom, an alkylene, alkenyl or hetero alkylene group, in which the CH2 group is substituted with a NH group, where the said groups can be optionally substituted with OH, =O or CH2OH groups, X1, X2, X3, X4 and X5 independently represent nitrogen atoms or groups of formula CH or CR4, Cy is cycloalkylene or heterocycloalkylene group containing at least one nitrogen atom, R1 is a hydrogen atom, an alkyl or alkyloxy group, R2 is a halogen atom, a hydroxy group, an alkyl or heteroalkyl residue, where the said groups can be optionally substituted with OH, NH2 groups and/or a =O group, R3 is a group of formula -B-Y, in which B denotes an alkylene, alkenyl or heteroalkylene group, where the said groups can be optionally substituted with OH, NH2, COOH groups or a =O group, and Y is an optionally substituted phenyl, optionally substituted heteroaryl group containing 5 or 6 ring atoms, or an optionally substituted bicyclic heterocycle in which one ring is phenyl or pyridyl, and the other is a 5-, 6- or 7-member heteroaryl or heterocycloalkyl group which contains up to 3 heteroatoms selected from nitrogen, oxygen and sulphur atoms, R4 is a halogen atom, n equals 0, 1 or 2 and m equals 0 or 1, or their pharmaceutically acceptable salts, solvates and hydrates. The invention also relates to a pharmaceutical composition based on the formula I compound and use of the compound or the pharmaceutical composition to treat bacterial infections.

EFFECT: obtaining novel compounds possessing useful biological properties.

12 cl, 7 ex

Amide derivatives // 2396259

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compound of formula I where m equals 0 or 1; R1 represents halogeno, (C1-6)alkyl, (C1-6)alkoxy, amino-(C2-6)alkoxy, (C2-6)alkylamino-(C2-6)alkoxy, di-[(C1-6)alkyl]amino-(C2-6)alkoxy, (C1-6)alkoxy-(C2-6)alkoxy, carbamoyl-(C1-6)alkoxy, N-(C1-6)alkylcarbamoyl-(C1-6)alkoxy, amino-(C1-6)alkyl, (C1-6)alkylamino-(C1-6)alkyl, di(C1-6)alkyl]amino-(C1-6)alkyl, carbamoyl-(C1-6)alkyl, N-(C1-6)alkylcarbamoyl-(C1-6)alkyl, (C1-6)alkoxy-(C2-6)alkylamino, heteroaryloxy, heterocyclyl-(C1-6)alkyl, heterocyclyloxy or heterocyclyl-(C1-6)alkoxy, and where any heteroaryl or heterocyclyl group in substituent R1 probably can have 1 or 2 substituents, selected from hydroxy, halogeno, (C1-6)alkyl, (C1-6)alkoxy, (C2-6)alkanoyl, hydroxy-(C1-6)alkyl, (C1-6)alkoxy-(C1-6)alkyl, and where any of determined above R1 substituents, which contains CH2 group bound with 2 carbon atoms, or group CH3, bound with an atom of carbon or nitrogen, probably can have on each said CH2 or CH3 group one or more substituents, selected from halogeno, hydroxy, amino, oxo, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkinyl,. (C3-6)cycloalkyl, (C3-6)cycloalkoxy, (C1-6)alkoxy, (C1-6)alkoxy-(C1-6)alkyl, (C1-6)alkylsulphamoyl, heteroaryl, heteroaryl-(C1-6)alkyl and heterocyclyl, and where any heterocyclyl group in substituent R1 probably can have 1 or 2 oxo or tioxo substituents; R2 represents (C1-6)alkyl; R3 represents hydrogen; R4 represents (C3-6)cycloalkyl, (C1-6)alkyl or heteroaryl, and R4 probably can be substituted with one or more substituents, selected from halogeno, (C1-6)alkyl, (C1-6)alkoxy; and R5 represents hydrogen, halogeno or (C1-6)alkyl; or its pharmaceutically acceptable salt, to method of obtaining said compounds, to pharmaceutical composition for application in treatment of diseases mediated by based on them cytokines. Invention also relates to methods of inhibiting p38α-kinase enzymes, TNFα production and production of cytokines.

EFFECT: obtained and described are novel compounds, which can be applied in treatment of medical conditions mediated by cytokines.

14 cl, 31 ex, 9 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, pharmaceutical compositions based on the said compounds, as well as methods of using said compounds in preparing medicinal agents.

EFFECT: obtaining compounds and a composition which can inhibit phosphatase cdc25, particularly phosphatase cdc25-C and can be particularly used for treating cancer.

12 cl, 56 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 2,4-di(hetero)arylaminopyrimidine of general formula I or its pharmaceutically acceptable salt, possessing properties of ZAP-70 inhibitors. In compounds of formula I: Z stands for =CR2-; each of radicals R0 and R1 represents hydrogen; R2 represents (C1-C4)alkoxy; R3 represents -SO2NH2; or R1 and R2 form together with C-atoms, to which they are bound, 5-7-member non-aromatic carbocyclic or heterocyclic residue, where said heterocyclic residue includes 1 or 2 heteroatoms, selected from N and O, and heterocyclic residue, containing 1-2 atoms of oxygen can be substituted with fluorine atoms; R4 and R6 represent hydrogen, R5 represents hudrogen, halogen, (C1-C4)alkyl or CF3; one of R7, R8 and R9 represents NR10R11, and one or two others represent hydrogen, halogen, COOH, CF3 or (C1-C4)alkyl; R10 and R11 independently represents hydrogen or (C1-C4)alkyl. Invention also relates to methods of obtaining compounds.

EFFECT: compounds can be applied, for instance in case of acute or chronic rejection of organ or tissue, in treatment of atherosclerosis and other diseases, when inhibition of ZAP-70 is of importance.

9 cl, 7 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess properties inhibiting HIV replication, of general formula (I) , in form of E-isomer, in which -a1=a2-a3=a4- represents bivalent radical of formula -CH=CH-CH=CH- (a-1); -b1=b2-b3=b4. Represents bivalent radical of formula -CH=CH-CH=CH- (b-1); n equals 0; m equals 2; each of R1 radicals independently on each other stands for hydrogen atom; C1-6alkyl; R2a stands for cyanogroup; X1 stands for -NR1-; R3 represents C2-6alkenyl, substituted with cyanogroup; R4 stands for C1-6alkyl; R5 represents radical of formula -Y-Alk-L, -Alk'-Y-L or -Alk'-Y-Alk-L; each of radicals Alk or Alk' independently represents bivalent C1-6alkyl or C2-6 alkenyl group; L stands for aryl or Het; Y stands for NR1; -CH=N-O-; Het stands for 5- or 6-member fully saturated ring system, in which one, two or three ring elements represent heteroatoms, each of which is independently selected from group, including nitrogen, oxygen and sulphur, and in which other ring elements represent carbon atoms; and, if possible, any nitrogen ring element can be optionally substituted with C1-6alkyl; and ring system can be optionally bound with benzene ring; and in which any carbon atom of ring, including any carbon atom of optionally bound benzene ring, each independently can be substituted with substituent selected from such groups as halogen atom, C1-6alkyl, hydroxyC1-4alkyl, carboxyC1-4alkyl, C1-4 alkylcarbonyloxyC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, aryloxy, morpholinyl, aryl, Het1; Het1 stands for thienyl, isoxazolyl, thiadiazolyl, each of which can be optionally substituted with one or two C1-4alkyl radicals; Q stands for hydrogen atom; each aryl represents phenyl or phenyl, substituted with one, two substituents, each of which is independently selected from such groups as halogen atom, C1-6alkyl, C2-6alkinyl, cyano, polyhalogen C1-6alkyl or Het1, as well as to its pharmaceutically acceptable additive salts Invention also relates to pharmaceutical composition.

EFFECT: creation of novel compounds, which possess properties inhibiting HIV replication

5 cl, 7 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline, represented by formula , where R1 represents (1-6C)alkyl; R2 represents halogen, (1-4C)alcoxy; R3 represents OH, NO2, CN, fluoridated with (1-4C)alkoxy, (1-4C)alkoxy(2-4C)alkoxy. hydroxy(2-4C)alkoxy, (1-4C)alkoxycarbonyl, R7, R8-amino, R9, R10-amino, R9, R10-aminocarbonyl, R9, R10-aminosulfonyl or phenyl(1-4C)alkoxy, where phenyl ring in composition phenyl(1-4C)alkoxy is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R4 represents R11-phenyl or R11-(4-5C)heteroaryl, which represents heteroaromatic group, containing 4-5 carbon atoms and at least one heteroatom, selected from N and S, where phenyl or heteroaryl group is optionally additionally substituted with one or several substituents, selected from nitro, (1-4C)alkyl, (1-4C)alkoxy; R7 represents H, (1-4C)alkyl; R8 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy(1-4C)alkylcarbonyl, furylcarbonyl; phenyl(1-4C)alkylcarbonyl, where phenyl ring is optionally substituted with one or several substituents, selected from (1-4C)alkoxy; R9 and R10 are not necessarily selected from H, (1-6C)alkyl and (1-4C)alkoxy(2-4C)alkyl; or R9 and R10 can be bound together with formation of morpholinyl ring; R11 represents H, R12, R13-amino, R14, R15-aminocarbonyl or R14, R15-aminosulfonyl; R12 represents H; R13 represents (1-4C)alkylsulfonyl, (1-4C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyperazinyl(1-4C)alkylcarbonyl; R14 and R15 are independently selected from H, (1-6C)alkyl, (1-4C)alkoxy(2-4C)alkyl and imidazolyl(1-4C)alkyl; X represents O or R16-N; Y represents CH2 or C(O);Z represents CN; R16 represents H, (1-4C)alkyl, (1-4C)alkylcarbonyl; or their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition, as well as to application of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydrochinoline derivatives by any of i.i. 1-10.

EFFECT: obtaining novel biologically active compounds, which possess agonistic activity with respect to FSH receptor.

13 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline or quinazoline derivatives of general formula

Ib, where R1 is C1-6-alkyl or C1-6-alkoxy; X is N or CH; R3 and R4 independently denote hydrogen, C1-6-alkyl, C1-6-alkylsulphonyl or a group of formula (IIa), where A is oxygen or sulphur; D is -(CH2)t, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur, (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or a group of formula (IIb), where A is oxygen or sulphur; D is -(CH2)t-, -(CH2)tO- or -O(CH2)t, where t equals 0, 1, 2, 3 or 4; and E is C1-6-alkyl, C3-7-cycloalkyl, or a 3-7-member monocyclic aromatic ring or a 6-10-member bicyclic aromatic ring in which 1-3 carbon atoms in the ring(s) are optionally substituted with a heteroatom which is independently selected from nitrogen, oxygen and sulphur (optionally substituted with 1 or 2 substitutes independently selected from halogen, C1-6-alkyl, CF3, cyano, hydroxy and C1-6-alkoxy); or R3 and R4 together with the nitrogen atom with which they are bonded form a 3-7-member ring or a 6-10-member bicyclic ring which can be saturated, partially saturated or unsaturated and contain 1, 2 or 3 heteroatoms selected from nitrogen, sulphur and oxygen, where each group is optionally substituted with 1 or 2 substitutes selected from oxo, C1-6-alkyl, C1-6-alkoxy, aryl and aryl-C1-6-alkyl (where aryl and aryl-C1-6-alkyl are also optionally substituted with 1 or 2 with C1-6-alkyls or C1-6-alkoxy). The invention also relates to use of formula Ib compounds in preparing a medicinal agent, to a pharmaceutical composition based on formula Ib compound and preparation method thereof.

EFFECT: obtaining novel quinoline and quinazoline derivatives having high affinity to 5-HT1-receptors.

12 cl, 171 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) and their pharmaceutically acceptable addition salts having HIV replication inhibiting properties. In formula (I), R1 is halogen; R2 and R3 each independently denotes C1-6-alkyl. The invention also relates to a method for synthesis of said compounds and a pharmaceutical composition.

EFFECT: increased effectiveness of derivatives.

7 cl, 6 ex

FIELD: medicine.

SUBSTANCE: invention relates to novel pyrimidine derivatives of formula (I) or their pharmaceutically acceptable salts which possess inhibiting activity with respect to focal adhesion kinase (FAK), proteintyrosinekinase ZAP-70, receptor of insulin-like growth factor 1 (IGF-1R), tyrosinekinase activity of anaplastic lymphoma (ALK) and fusion protein NPM-ALK. In formula (I) , R0, R1 and R2 independently represent hydrogen, C1-C8 alkyl, 5- or 6-member heterocycle, containing 1,2 or 3 heteroatoms, selected from N, O and S, C1-C8alkoxy group, C1-C8alkylsulphinyl, C1-C8alkylsulphonyl, C5-C10arylsulphonyl, halogen, carbamoyl, sulphamoyl, etc.; R3 represents C1-C8alkylsulphinyl, C1-C8alkylsulphonyl, C5-C10arylsulphonyl, carbamoyl or sulphamoyl; R4 represents hydrogen or C1-C8alkyl; R5 represents chlorine or bromine; R6 represents hydrogen; R7, R8, R9 and R10 independently represent C1-C8alkyl, C5-C10aryl, possibly substituted by 5- or 6-member heterocycle, containing 1, 2 or 3 heteroatoms, selected from N, O and S, where substituents are selected from C1-C8alkyl, hydroxy, hydroxy-C1-C8alkyl, C1-C8alkoxy C1-C8alkyl, cyano, oxo, C1-C8alkylamino, diC1-C8alkylamino, carbamoyl, C1-C8alkylcaronyl, 5-10-member heterocycle, containing 1, 2 or 3 heteroatoms, selected from N and O, which is probably substituted by C1-C8alkyl; C1-C8alkoxy group, halogen- C1-C8alkoxy group, etc; A represents C. Invention also relates to pharmaceutical composition and to application of compounds of formula (I) for preparation of medication.

EFFECT: novel compounds possess useful biologic activity.

15 cl, 61 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) , where Z means where R means hydrogen, C4-C6cycloalkyl group attached either through one of ring carbon atoms, or through a lower alkylene group attached to the ring, or a linearly chained or branched lower alkyl group or a lower hydroxyalkyl group, or a lower aminoalkyl group, or a phenyl(lower alkyl) group optionally substituted with 1-2 substitutes chosen from lower alkyl, lower alkoxy, halogen and hydroxy, or heteroaryl(lower alkyl)group where heteroaryl is chosen from the group consisting from thienyl, substituted with lower alkyl group, imidazolyl, and thiazolyl substituted with the lower alkyl group; n means 0 or 1; or Z means a group where R means the lower alkyl group; X1 means methylene or NH group; and X2 means methylene; or X1 means methylene and X2 means methylene or a bond; or X1 means methylene, and X2 means O, S or a bond; Y1 means methylene, and Y2 means methylene, vinylene, ethylene, or a bond; Ar1 means unsubstituted or substituted phenyl; Ar2 means unsubstituted or substituted phenyl, unsubstituted or substituted thienyl, unsubstituted or substituted furyl, unsubstituted or substituted pyridyl; and when Ar1 and Ar2 are substituted, each Ar1 and Ar2 are independently substituted with one or more substituted chosen from lower alkyl, lower alkoxy, hydroxy, lower hydroxyalkyl, halogen, di- and trihaloalkyl, di- and trihaloalkoxy, mono- and dialkylamino, alkilthio, alkyl ester and nitro; provided that Ar1 and Ar2 do not simultaneously mean unsubstituted phenyl; W means oxygen or sulphur; or to their pharmaceutically acceptable salts; provided those specified in cl. 1 of the patent claim. Besides the invention concerns the compounds chosen from the group, to compounds of formula (I), to pharmaceutical compositions, to a method of inhibition of monoamine receptor activity, to a method of inhibition of monoamine receptor activation, to a method of treating a diseased state associated with serotonin receptor, to a method of treating schizophrenia, to a method of treating migraine, and also to a method of treating psychosis.

EFFECT: preparation of the new biologically active compounds capable to inhibit monoamine receptor activity.

65 cl, 140 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry, and specifically to compounds of general formula I , where A is an oxygen atom, an alkylene, alkenyl or hetero alkylene group, in which the CH2 group is substituted with a NH group, where the said groups can be optionally substituted with OH, =O or CH2OH groups, X1, X2, X3, X4 and X5 independently represent nitrogen atoms or groups of formula CH or CR4, Cy is cycloalkylene or heterocycloalkylene group containing at least one nitrogen atom, R1 is a hydrogen atom, an alkyl or alkyloxy group, R2 is a halogen atom, a hydroxy group, an alkyl or heteroalkyl residue, where the said groups can be optionally substituted with OH, NH2 groups and/or a =O group, R3 is a group of formula -B-Y, in which B denotes an alkylene, alkenyl or heteroalkylene group, where the said groups can be optionally substituted with OH, NH2, COOH groups or a =O group, and Y is an optionally substituted phenyl, optionally substituted heteroaryl group containing 5 or 6 ring atoms, or an optionally substituted bicyclic heterocycle in which one ring is phenyl or pyridyl, and the other is a 5-, 6- or 7-member heteroaryl or heterocycloalkyl group which contains up to 3 heteroatoms selected from nitrogen, oxygen and sulphur atoms, R4 is a halogen atom, n equals 0, 1 or 2 and m equals 0 or 1, or their pharmaceutically acceptable salts, solvates and hydrates. The invention also relates to a pharmaceutical composition based on the formula I compound and use of the compound or the pharmaceutical composition to treat bacterial infections.

EFFECT: obtaining novel compounds possessing useful biological properties.

12 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of 5-(4-[4-(5-cyano-3-indolyl)butyl]-1-piperazinyl)benzofuran-2-carboxamide and/or one of its physiologically acceptable salts, characterised by that a compound of formula (I),

, in which L is CI, Br, I, SO2F, SO2CF3, SO2C2F5, is reacted with 3-(4-piperazin-1-ylbutyl)indole-5-carbonitrile through transition metal catalysed combination through complex compounds of Pd and/or that the formed 5-(4-[4-(5-cyano-3-indolyl)butyl]-1-piperazinyl)benzofuran-2-carboxamide is converted to one of its acid addition salt through treatment with an acid, and to a second method which is characterised by that a formula (II) compound, as a base or salt HX (where X=Cl, Br), is reacted with 3-(4-oxobutyl)-1H-indole-5-carbonitrile through reductive amination, and or that 5-(4-[4-(5-cyano-3-indolyl)butyl]-1-piperazinyl)benzofuran-2-carboxamide is converted to one of its acid addition salt through treatment with an acid.

EFFECT: obtaining a compound which is a 5-HT1A receptor agonist.

4 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel thiophene derivatives of formula (I): ,

where the ring system A is characterised by formula ,

R1 denotes hydrogen, C1-C5alkyl or C1-C5alkoxy, R2 denotes hydrogen, C1-C5alkyl, C1-C5alkoxy or trifluoromethyl, R3 denotes hydrogen, hydroxy(C1-C5)alkyl, 2,3-dihydroxypropyl, di(hydroxy(C1-C5)alkyl)(C1-C5)alkyl, -CH2-(CH2)n-COOH, -CH2-(CH2)n-CONR31R32, hydroxy, C1-C5alkoxy, hydroxy(C2-C5)alkoxy, di(hydroxy(C1-C5)alkyl)(C1-C5)alkoxy, 1-glyceryl, 2-glyceryl, 2-hydroxy-3-methoxypropoxy, -OCH2-(CH2)m-NR31R32, 2-pyrrolidin-1-ylethoxy, 3-pyrrolidin-1-ylpropoxy, 3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy, 2-morpholin-4-ylethoxy, 3-morpholin-4-ylpropoxy, 3-[(pyrrolidin-3-carboxylic acid)-1-yl]propoxy, 3-[(pyrrolidin-2-carboxylic acid)-1-yl]propoxy or 2-amino-3-hydroxy-2-hydroxymethylpropoxy; R31 denotes hydrogen, methyl, ethyl, 1-propyl, 2-propyl, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethylethyl, 2-(C1-C5)alkoxyethyl, 3-(C1-C5)alkoxypropyl, 2-aminoethyl, 2-(C1-C5alkylamino)ethyl or 2-(di-(C1-C5alkyl)amino)ethyl; R32 denotes hydrogen, methyl, ethyl, m equals 1 or 2; n equals 1; and R4 denotes hydrogen, (C1-C5)alkyl or halogen, and configuration isomers thereof, such as optically pure enantiomers, mixtures of enantiomers, such as racemates, diastereomers, mixtures of diastereomers, diastereomeric racemates, and mixtures of diastereomeric racemates, as well as salts of said compounds of formula (I), synthesis thereof and use as therapeutically active compounds.

EFFECT: compounds have the effect of immunosuppressive agents.

20 cl, 2 tbl, 46 ex

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