Diazepane derivatives as modulators of chemokine receptors

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of diazepane of formula , where A, X, R3, R4, R5, R6, R8, R9, R10, R11, R12, R13, n and m have values, given in description and formula of invention, as well as their physiologically acceptable salts. Said compounds are antagonists of chemokine receptors CCR-2, CCR-5 and/or CCR-3 receptor and can be used in medicine as medications.

EFFECT: obtaining novel diazepane derivatives.

20 cl, 505 ex, 4 tbl

 

The text descriptions are given in facsimile form.

1. The compounds of formula (I)

where a denotes a phenyl, naphthyl or pyridinyl, it called phenyl, naphthyl or pyridinyl optionally substituted from one to three substituents, independently selected from the group comprising halogen, benzyloxy, C1-6alkyl, C1-6alkoxygroup and Gialos1-6alkoxygroup, or the said phenyl optionally substituted C1-6alkylenedioxy;
X represents-N(R1)(R2or-N+(R1)(R2)(R7);
i) R1and R2denote, independently of one another, hydrogen, C1-6alkyl, C3-6alkenyl, C3-6quinil, hydroxys 2-6alkyl, C1-6alkoxyl2-6alkyl, C3-7cycloalkyl,3-7cycloalkyl1-6alkyl, C7-10bicycloalkyl, panels1-3alkyl, heteroaryl1-3alkyl, heterocyclyl or heterocyclyl1-6alkyl, where cycloalkyl named With the3-7cycloalkyl and named With the3-7cycloalkyl1-6of alkyl, phenyl named finals1-3of alkyl, heteroaryl named heteroaryl1-3the alkyl and heterocyclyl named heterocyclyl and named heterocyclic1-6the alkyl optionally substituted from one to three substituents, independently selected from the group comprising Rd; or
R1and R2together with the nitrogen atom to which they are attached, form heterocyclyl, optionally substituted from one to three substituents, independently selected from the group comprising Rdand one of the ring carbon atoms named heterocyclyl formed R1and R2, optionally substituted carbonyl group; and/or
one of the ring carbon atoms heterocyclyl formed R1and R2may be a ring carbon atom of another ring which is C3-7cycloalkyl or heterocyclyl, with one or two ring carbon atom called another ring optionally substituted carbonyl group, and named the other ring without having substituted C 1-6by alkyl;
R3and R4denote independently of one another, hydrogen, a hydroxy-group, C1-6alkyl, C1-6alkoxygroup, C3-7cycloalkyl, C3-7cycloalkyl1-6alkyl, C1-6alkoxycarbonyl, carboxyl group, hydroxys1-6alkyl, C1-6alkoxyl1-6-alkyl, halogen or Gialos1-6alkyl; or
ii) R1denotes hydrogen, C1-6alkyl, C3-6alkenyl, C3-6quinil, hydroxys1-6alkyl, C1-6alkoxyl1-6alkyl, C3-7cycloalkyl, C3-7cycloalkyl1-6alkyl, C7-10bicycloalkyl, panels1-3alkyl, heteroaryl1-3alkyl, heterocyclyl or heterocyclyl1-6alkyl, where cycloalkyl named C3-7cycloalkyl and named C3-7cycloalkyl1-6of alkyl, phenyl named finals1-3of alkyl, heteroaryl named heteroaryl1-3the alkyl and heterocyclyl named heterocyclyl and named heterocyclic1-6the alkyl optionally substituted from one to three substituents, independently selected from the group comprising Rd;
R3denotes hydrogen, C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkyl1-6alkyl, halogen or Gialos1-6alkyl;
R2and R4together with the nitrogen atom that is attached to R2carbon atom that is attached to R4and alkalinous group between said nitrogen atom and the said carbon atom, if it exists at all, form heterocyclyl, optionally substituted from one to three substituents, independently selected from the group comprising C1-6alkyl and fluorine;
R5and R6denote independently of one another, hydrogen or C1-6alkyl;
R7represents C1-6alkyl;
R8, R9, R10, R11, R12and R13denote independently from each other hydrogen or C1-6alkyl;
Rddenotes a hydroxy-group, cyano, NRaRb, halogen, C1-6alkyl, Gialos1-6alkyl, hydroxys1-6alkyl, C1-6alkoxygroup, C1-6alkoxyl1-6alkyl, C3-7cycloalkyl, C1-6alkoxycarbonyl, acyl, -C(O)NRaRb, -NRa-C(O)-Rb, -NRa-C(O)ORb, -NRa-C(O)-NRb-NRa-SO2-Rb, -NRa-SO2-NRbRc, -OC(O)NRaRb, -OC(O)ORaC1-6alkylsulfonyl, C1-6alkylsulfonyl, C1-6allylthiourea, phenyl, panels1-3alkyl, heteroaryl, heteroaryl1-3alkyl and heterocyclyl, and phenyl named phenyl and named finals1-3of alkyl, heteroaryl named heteroaryl and named heteroaryl1-3the alkyl and heterocyclyl optionally substituted from one to three mandated what teli, independently selected from the group comprising a hydroxy-group, cyano, NRaRb, halogen, C1-6alkyl, Gialos1-6alkyl, hydroxys1-6alkyl, C1-6alkoxycarbonyl, acyl, -C(O)NRaRb, -NRa-C(O)-Rb, -NRa-C(O)-ORb, nra-C(O)-nrb, -NRa-SO2-Rb, -NRa-SO2-NRbRc, -OC(O)NRaRb, -OC(O)ORaC1-6alkylsulfonyl, C1-6alkylsulfonyl and C1-6allylthiourea, and one or two ring carbon atom heterocyclyl optionally substituted carbonyl group;
Ra, Rband Rcindependently represent hydrogen or C1-6alkyl;
n denotes an integer from 0 to 3;
m denotes an integer from 0 to 3;
m+n denotes an integer from 1 to 5;
or their pharmaceutically acceptable salts;
where, if not specified,
the term "aryl" denotes phenyl or naphthyl;
the term "heterocyclyl" means non-aromatic, mono - or bicyclic radicals containing from four to nine ring atoms in which one to three ring atoms are heteroatoms independently selected from N, O or S(O)n(where n denotes an integer from 0 to 2), while the remaining atoms are carbon atoms;
the term "heteroaryl" denotes monocyclic or bicyclic radicals containing 5 cm to 10 ring atoms, and that includes from one to three ring heteroatoms independently selected from N, O and S with the remaining atoms are carbon atoms;
the term "acyl" refers to R-C(O)-, where R is a C1-6alkyl, Gialos1-6alkyl, C3-7cycloalkyl or3-7cycloalkyl1-6alkyl.

2. Compounds according to claim 1, where
R3and R4denote independently from each other hydrogen, C1-6alkyl, C3-7cycloalkyl,3-7cycloalkyl1-6alkyl, halogen or Gialos1-6alkyl;
R8, R9, R10, R11, R12and R13represent hydrogen;
Rddenotes a hydroxy-group, cyano, NRaRb, halogen, C1-6alkyl, Gialos1-6alkyl, hydroxys1-6alkyl, C1-6alkoxygroup, C1-6alkoxyl1-6alkyl, C1-6alkoxycarbonyl, acyl, -C(O)NRaRb, -NRaC(O)-Rb, -NRa-C(O)-ORb, -NRa-C(O)-NRb, NRa-SO2-Rb, -NRa-SO2-NRbRc, -OC(O)NRaRb, -OC(O)ORaC1-6alkylsulfonyl, C1-6alkylsulfonyl, C1-6allylthiourea, phenyl, panels1-3alkyl, heteroaryl, heteroaryl1-3alkyl and heterocyclyl, and phenyl named phenyl and named finals1-3of alkyl, heteroaryl named heteroaryl and named heteroaryl1-3the alkyl and heterocyclyl the optional is tion substituted from one to three substituents, independently selected from the group comprising a hydroxy-group, cyano, NRaRb, halogen, C1-6alkyl, Gialos1-6alkyl, hydroxys1-6alkyl, C1-6alkoxycarbonyl, acyl, -C(O)NRaRb, -NRa-C(O)-Rb, -NRa-C(O)-ORb, -NRa-C(O)-NRb, -NRa-SO2-Rb, -NRa-SO2-NRbRc, -OC(O)NRaRb, -OC(O)ORaC1-6alkylsulfonyl, C1-6alkylsulfonyl and C1-6allylthiourea, and one or two ring carbon atom heterocyclyl optionally substituted carbonyl group.

3. Compounds according to claim 1, where a denotes a phenyl, optionally substituted from one to three substituents, independently selected from the group comprising halogen, benzyloxy, C1-6alkyl, C1-6alkoxygroup and Gialos1-6alkoxygroup, And or denotes phenyl, optionally substituted C1-6alkylenedioxy.

4. Compounds according to claim 1, where a denotes a phenyl, substituted by one or two halogen atoms, independently selected from the group comprising chlorine and fluorine.

5. Compounds according to claim 1, where a denotes a phenyl, substituted with two halogen atoms, independently selected from the group comprising chlorine and fluorine at position 3, 4 or 3, 5.

6. Compounds according to claim 1, where X represents-N(R1)(R2).

7. Compounds according to claim 6, where at the very the least one of R 1and R2is other than hydrogen.

8. Compounds according to claim 6, where R1denotes hydrogen, C1-6alkyl or hydraxis2-6alkyl, and R2represents C3-7cycloalkyl, heterocyclyl, heterocyclyl1-6alkyl, C7-10bicycloalkyl, hydroxys2-6alkyl or C1-6alkoxyl2-6alkyl, where cycloalkyl and heterocyclyl named heterocyclyl and named heterocyclic1-6the alkyl optional substituted with one or two substituents, independently selected from the group comprising C1-6alkyl, hydroxy-group, heteroaryl and C1-6alkoxygroup.

9. Compounds according to claim 6, where R1denotes hydrogen and R2means heterocyclyl.

10. Compounds according to claim 6, where m+n denotes an integer of 1 or 2.

11. Compounds according to claim 6, where R3, R4, R5and R6denote hydrogen.

12. Compounds according to claim 6, where R1and R2together with the nitrogen atom to which they are attached, form heterocyclyl, optionally substituted from one to three substituents, independently selected from the group comprising Rdand one of the ring carbon atoms named heterocyclyl formed R1and R2, optionally substituted carbonyl group; and/or
one of the ring carbon atoms heterocyclyl formed R1and R2, can the be ring carbon atom of another ring, which is3-7cycloalkyl or heterocyclyl, with one or two ring carbon atom called another ring optionally substituted carbonyl group, and named another ring without having substituted C1-6the alkyl.

13. The connection section 12, where heterocyclyl formed R1and R2together with the nitrogen atom to which they are attached, is a monocyclic radical, containing five or six carbon atoms, in which one or more ring atoms in addition to nitrogen atom may be heteroatoms independently selected from N, O and S(O)n(where n denotes an integer from 0 to 2).

14. The connection section 12, where heterocyclyl formed R1and R2together with the nitrogen atom to which they are attached, represents piperidyl, pyrrolidinyl, piperazinil, morpholinyl, thiomorpholine or 1,1-dioxothiazolidine.

15. The connection section 12, where heterocyclyl formed R1and R2together with the nitrogen atom to which they are attached, represents piperidyl or pyrrolidinyl.

16. The connection section 12, where heterocyclyl formed R1and R2together with the nitrogen atom to which they are attached, optionally substituted by one or two substituents, independently selected from the group comprising a hydroxy-group, phenyl and GI is roxis 1-6alkyl, and/or
one of the ring carbon atoms heterocyclyl formed R1and R2can enter another ring which is a 5 - or 6-membered monocyclic heterocyclyl, with one or two ring carbon atom called another ring optionally substituted carbonyl group.

17. The connection section 12, where m+n denotes an integer from 1 to 3.

18. The connection section 12, where R3, R4, R5and R6denote hydrogen.

19. Compounds according to claim 1, including:
1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-(4-piperidine-1-libutil)-[1,4]diazepan-5-he,
1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-(3-piperidine-1-ylpropyl)-[1,4]diazepan-5-he,
1-[(E)-3-(4-Chloro-3-forfinal)acryloyl]-4-(3-piperidine-1-ylpropyl)-[1,4]diazepan-5-he,
8-(3-{4-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-7-oxo-[1,4]diazepan-1-yl}propyl)--1,3,8-triaza-Spiro[4.5]decane-2,4-dione,
1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-[3-(4-hydroxy-4-phenylpiperidine-1-yl)propyl]-[1,4]diazepan-5-he,
(+/-)-1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-[3-(3-hydroxypiperidine-1-yl)propyl]-[1,4]diazepan-5-he,
8-(3-{4-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-7-oxo-[1,4]diazepan-1-yl}propyl)-1-oxa-3,8-diaza-Spiro[4.5]decane-2-it,
1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-[3-(tetrahydropyran-4-ylamino)ethyl]-[1,4]diazepan-5-he,
(S)-1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-[3-(2-hydroxyethylpyrrolidine-1-yl)ethyl]-[1,4]diazepan-5-he, or
1-[(E)-3-(3,4-Dichlorophen the l)acryloyl]-4-(2-pyrrolidin-1-retil)-[1,4]diazepan-5-he.

20. Compounds according to claim 1, including:
1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-[3-((-,CIS)-3-hydroxy-4-methylpiperidin-1-yl)propyl]-[1,4]diazepan-5-he,
1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-[3-(3-hydroxy-4,4-dimethylpiperidin-1-yl)propyl]-[1,4]diazepan-5-he,
(CIS)-1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-[3-(3-hydroxy-5-methylpiperidin-1-yl)propyl]-[1,4]diazepan-5-he,
1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-[2-hydroxy-3-(3-hydroxy-4-methylpiperidin-1-yl)propyl]-[1,4]diazepan-5-he,
1-[(E)-3-(3,4-Dichlorophenyl)acryloyl]-4-[(S)-2-hydroxy-3-((-)-4-hydroxy-6-Aza-Spiro[2.5]Oct-6-yl)propyl]-[1,4]diazepan-5-he,
1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-[(S)-2-hydroxy-3-(3-hydroxy-4,4-dimethylpiperidin-1-yl)propyl]-[1,4]diazepan-5-he,
1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-[(S)-2-hydroxy-3-(CIS-3-hydroxy-5-methylpiperidin-1-yl)propyl]-[1,4]diazepan-5-he,
1-[(E)-3-(4-Chloro-3-forfinal)acryloyl]-4-[4-((-)-4-hydroxy-6-Aza-Spiro[2.5]Oct-6-yl)butyl]-[1,4]diazepan-5-he,
(CIS)-1-[(E)-3-(3-Chloro-4-forfinal)acryloyl]-4-[4-(3-hydroxy-5-methylpiperidin-1-yl)butyl]-[1,4]diazepan-5-he,
1-[(E)-3-(3-Chlorophenyl)acryloyl]-4-[3-((-)-4-hydroxy-6-Aza-Spiro[2.5]Oct-6-yl)propyl]-[1,4]diazepan-5-he or
1-[(E)-3-(5,6-Dichloropyridine-3-yl)acryloyl]-4-[3-((-)-4-hydroxy-6-Aza-Spiro[2.5]Oct-6-yl)propyl]-[1,4]diazepan-5-it.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula in which R1 denotes a) adamantyl, hydroxyadamantyl or trifluoromethylphenyl; R2 denotes hydrogen, methyl, ethyl or cyclopropyl; one of R3 and R4 denotes alkyl, cycloalkyl, haloalkyl or is absent, and the other denotes a) hydrogen, alkyl, pyridinyl, cycloalkyl, cycloalkylalkyl or haloalkyl; b) phenyl or phenyl substituted with one to three substitutes independently selected from fluorine, chlorine, bromine, haloalkyl and alkoxy group; c) phenylalkyl, where the phenylalkyl is optionally substituted with one to three halogens; e) naphthyl or tetrahydronaphthyl; f) phenylalkoxyalkyl; g) hydroxyalkyl; or h) pyridinyloxyalkyl or pyridinyloxyalkyl substituted with an cyano group; or R3 and R4 together with a carbon atom with which they are bonded form a cycloalkane or piperdine, where the cycloalkyl and piperidine are optionally substituted with one to three substitutes independently selected from aryl and arylalkyl; one of R5 and R6 denotes hydrogen, isopropyl, isobutyl or haloalkyl, and the other denotes hydrogen or is absent; and to pharmaceutically acceptable salts thereof, under the condition that 1,3-dihydro-4-phenyl-1-(3-(trifluoromethyl)phenyl)-2H-imidazol-2-one is excluded, and if one of R3 and R4 denotes methyl, ethyl, n-propyl or n-butyl, and the other denotes hydrogen or is absent, then R2 denote hydrogen or methyl. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds, having 11-beta-hydroxysteroid dehydrogenase 1 (11-beta-HSDI) inhibiting activity.

15 cl, 257 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: where X is selected from a group consisting of hydrogen, halogen, cyano, nitro, ethenyl, cyclopropyl, methyl, ethyl, isopropyl, methoxy and vinyl; Y denotes hydrogen or fluorine; R4 and R5 denote hydrogen or lower alkyl; one of R1 and R8 is selected from a group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl, and the other denotes hydrogen; one of R6 and R7 is selected from a group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl, and the other denotes hydrogen, cyano group or lower alkyl; R2 is selected from a group consisting of hydrogen, lower alkyl and substituted lower alkyl; R3 is selected from a group consisting of oxygen, sulphur and NNH(C=O)OR9; R9 denotes lower alkyl or substituted lower alkyl; where the term "substituted" denotes substitution with 1-5 substitutes independently selected from a group consisting of lower alkyl, lower alkenyl, lower alkynyl, dioxo-lower alkenyl, halogen, hydroxy, -CN, -CF3, -NH2, -N(H, lower alkyl), N(lower alkyl)2, aminocarbonyl, carboxy, -NO2, lower alkoxy, thio-lower alkoxy, lower alkylsulphonyl, aminosulphonyl, lower alkylcarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyl, lower alkylcarbonyl-NH, fluoro-lower alkyl, fluoro-lower alkoxy, lower alkoxy-carbonyl-lower alkoxy, carboxy-lower alkoxy, carbamoyl-lower alkoxy, hydroxy-lower alkoxy, -NH2-lower alkoxy, -N(H, lower alkyl)-lower alkoxy, -N(lower alkyl)2-lower alkoxy, benzyloxy-lower alkoxy, mono or di-lower alkyl, substituted with aminosulphonyl or lower alkyl, which can optionally be substituted with a halogen, hydroxy, -NH2, -N(H, lower alkyl) or -N(lower alkyl)2; the term "heteroaryl" denotes an aromatic heterocyclic ring system containing up to two rings; and the term "heterocycle" denotes a substituted or unsubstituted 5-8-member mono- or bicyclic, aromatic or non-aromatic hydrocarbon, where 1-3 carbon atoms are replaced with a heteroatom selected from a nitrogen, oxygen or sulphur atom; and pharmaceutically acceptable salts thereof or esters. The invention also relates to a pharmaceutical composition, use of compounds in claims 1-31, as well as to methods of producing compounds of formulae II and III.

EFFECT: obtaining novel biologically active compounds which inhibit interaction of MDM2 protein with a p53-like peptide.

38 cl, 186 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel cyclic N,N'-diarylthioureas or N,N'-diarylureas of general formula (1), their optic (R)- and (S)-isomers and their pharmaceutically acceptable salts - antagonists of androgenic receptors. In formula (1), where: X represents oxygen or sulfur atom; m=0 or 1, mR1 represents C1-C3alkyl; R2 and R3 represent hydrogen atom; or R2 and R3 together with carbon atom, to which they are bound, form group C=O; or represents group NH; R4 and R5 represent hydrogen atom; or R4 represents hydrogen atom, and R5 represents methyl; or R4 represents hydrogen atom, methyl, and R5 represents group Zn-Y-R6, in which n=1 or 2, Z represents CH2 or C=0 and Y- oxygen atom or N-CH3, or Y represents C=O, and Z represents CH2; R6 represents hydrogen atom, methyl, benzyl, hydroxygroup or R5 and R4 together with atoms, to which they are bound, form five or sic-member heterocycle, including, at least, oxygen or nitrogen atom, which can be substituted by methyl. Invention also relates to method of obtaining compounds.

EFFECT: invention relates to anti-cancer substance, pharmaceutical composition, medication and method of treating prostate cancer with application of invention compounds.

12 cl, 6 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to novel derivatives of quinolone or one pharmaceutically acceptable salts thereof, solvates thereof or solvates of salts thereof, having general formula I , in which R1 denotes fluorine, R3 denotes halogen, a hydroxy group or a C1-C4-alkoxy group, R4 denotes C1-C6-alkyl or C3-C8-cycloalkyl, where the alkyl can contain 1-3 substitutes, and the substitutes are independently selected from a group comprising halogen or trifluoromethyl, and where the cycloalkyl can contain 1-3 halogen atoms as substitutes, or R3 and R4 together with atoms to which they are bonded form a ring with a group of formula , in which * indicates a site for bonding with a carbon atom, and # indicates a site for bonding with a nitrogen atom, R7 and R8 independently denote halogen, trifluoromethyl, a monofluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, C1-C3-alkyl or C1-C3-alkoxy group, and R9 denotes hydrogen, halogen or C1-C3-alkyl, or R8 denotes a trifluoromethoxy group, and R7 and R9 denote hydrogen, R10 denotes a group of formula or , in which * indicates a site for bonding with a carbon atom, R2 is bonded in position 3 or 4 and denotes a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkyl, C1-C4-alkoxycarbonyl, C3-C6-cycloalkylcarbonyl or optionally hydroxy-substituted C1-C6-alkylaminocarbonyl, where the alkyl is substituted with one substitute and the substitute is selected from a group comprising a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkoxycarbonyl and 2-oxopyrrolidin-1-yl, R5 and R6 are independently bonded in positions 3, 4 or 5 and independently denote hydrogen, hydroxy group, methyl or ethyl, and Y denotes a methylene group or an oxygen atom. The invention also relates to methods of producing a compound of formula I, a medicinal agent based on the compound of formula I, use of the compound of formula I and a method of fighting viral infections.

EFFECT: novel substituted quinolone derivatives which are useful in treating viral diseases are obtained.

11 cl, 1 tbl, 69 ex

FIELD: medicine.

SUBSTANCE: invention refers to indole-3-yl-carbonyl-spiro-piperidine derivatives which have an effect of Vla-receptor antagonists and are presented by Formula I: where a tail spiropiperidine group A and residual R1, R2 and R3 are such as specified in the patent claim.

EFFECT: higher efficiency of applying the compounds in drugs effective in dysmenorrhea, hypertension, chronic heart failure, inadequate vasopressin secretion, hepatic cirrhosis, nephrotic syndrome, obsessive-compulsive disorder, anxious and depressive disorders.

22 cl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel indol-3-yl-carbonyl-asaspiro-derivatives of formula I: where R1 represents H,-(CH2)m-Ra, where Ra represents NRiRii, phenyl, possibly substituted by one or more than one B, -(CH2)n-(CO)-Rb , where Rb represents NRiRii; there exists one or more than one R2 , where each R2 is the same or different and represents one or more than one H, in halogen way; R3 represents H, C1-6-alkyl; B represents in halogen way; Ri and Rii each independently represents H, C1-6-alkyl, C1-6alkyl-NRiiiRiv; Riii and Riv each independently represents C1-6alkyl; m equals 1-6; n equals 1-4; A represents group : where R4 represents H or C1-6alkyl; R5 represents phenyl, possibly substituted in halogen way; or its pharmaceutically acceptable salt; on condition that 1-(1H-indol-3-yl-carbonyl)-4-(1,3-dioxolan-2-yl)pyperidine is excluded.

EFFECT: compounds demonstrate antagonistic activity with respect to Via vasopressin receptor, which makes it possible to apply them for obtaining pharmaceutical composition.

22 cl, 4 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof where R1 and R2 together denote a group selected form groups of formula (III-1): , where R9 denotes 1) a lower alkyl group, optionally substituted with a halogen atom or lower alkoxy group, 2) an aryl group, 3) an aralkyl group, 4) a heteroarylalkyl group, 5) a heteroaryl group, where the aryl, aralkyl, heteroarylalkyl and heteroaryl groups can be substituted with a halogen atom, lower alkyl group, optionally substituted with a lower alkoxy group or 1-3 halogen atoms, lower alkoxy group, optionally substituted with 1-3 halogen atoms, cyano group, hydroxy group, alkylsulphonyl group, cycloalkylsulphonyl group, aryl group, heteroaryl group, alkylaminocarbonyl group, alkanoyl amino group, alkyl amino group or dialkylamino group; R10 denotes a lower alkyl group, optionally substituted with 1-3 halogen atoms, or a lower alkylsulphonyl group; X9-X12 denotes a carbon atom or a nitrogen atom, where the carbon atom can be independently substituted with a lower alkyl group, optionally substituted with a halogen atom or a lower alkoxy group, lower alkoxy group, optionally substituted with a halogen atom, or a cyano group or a halogen atom; R3 denotes a) a group of formula (II-1): (ii-U where R4 and R5, taken together with a nitrogen atom, form a 5- or 6-member monocyclic ring, where the monocyclic ring may contain a substitute in form of a lower alkyl group, m1 equals 3; or b) a group of formula (II-2): , where R6 denotes a lower alkyl group or cycloalkyl group; m2 equals 1 or 2; X1-X4 all denote carbon atoms, or one of X1-X4 denotes a nitrogen atom and the rest denote carbon atoms; and where "heteroaryl" in each case relates to a 5- or 6-member aromatic ring containing 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and a sulphur atom. The invention also relates to a histamine H3 receptor antagonist or inverse agonist, as well as a preventive or medicinal agent.

EFFECT: obtaining novel biologically active compounds, having histamine H3 receptor antagonist or inverse agonist activity.

11 cl, 8 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to indol-3-yl-carbonyl-spiro-piperadine derivatives used as V1a receptor antagonists and which have formula I: , where the spiro-piperadine A head group and residues R1, R2 and R3 are as defined in claim 1 of the invention. The invention also pertains to pharmaceutical compositions which contain such compounds and use thereof in preparing medicines with V1a receptor antagonist activity.

EFFECT: high activity of derivatives.

37 cl, 1 tbl, 285 ex

FIELD: chemistry.

SUBSTANCE: described are spirocyclic derivatives of cyclohexane of general formula . Values of radicals are given in the formula of invention. The compounds have affinity to the ORL1 receptor and can be used for treating abstinence syndrome (withdrawal syndrome) and pain. Also described is a medicinal agent and use of formula (I) compounds for preparing respective medicinal agents.

EFFECT: increased effectiveness of using the compounds.

13 cl, 17 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), their enatiomers, racemates and pharmaceutically acceptable salts, as well as a pharmaceutical composition based on said inhibitors and method of treating, preventing or suppressing inflammation and other conditions which are mediated by activity of leukotriene A4-hydrolase. In general formula (II) , X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is O; Z is chosen from a group which consists of O and a bond; W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to the nitrogen atom which is bonded to the said W; R4 is chosen from a group which consists of H, OCH3 and Cl; R6 is H or F; and R2' and R3' are each independently chosen from a group which consists of: A) H, C1-7alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-7alkyl, where each of substitutes (A) is independently substituted with 0 or 1 RQ, where each of said RQ is a carbon atom substitute, which is at least one carbon atom, separate from nitrogen atom; B) HetRa substitute; C) -C1-7alkyl-C(O)Rx; H) -C0-4alkyl-Ar5, where Ar5 is a 5-member heteroaryl, which has one heteroatom, chosen from a group >NRY, and 0 or 1 additional heteroatom -N=, and optionally contains two carbonyl groups, and optionally benzo-condensed; I) -C0-4alkyl-Ar5' , where Ar5' is a 5-member heteroaryl, which contains 3 or 4 nitrogen atoms; M) SO2C1-4alkyl; alternatively, R2' and R3', taken together with a nitrogen atom with which they are bonded, form a heterocyclic ring which contains at least one heteroatom, which is the said bonded nitrogen atom, where the said heterocyclic ring is chosen from a group which consists of i) 4-7-member heterocyclic ring HetRb, where the said 4-7-member heterocyclic ring HetRb has one heteroatom, which is the said bonded nitrogen atom, and is substituted with 0, 1 or 2 identical or different substitutes, where the said substitutes are chosen from a group which consists of -RY, -CN, -C(O)RY, -C0-4alkyl-CO2RY, -C0-4alkyl-C(O)CO2RY, -C0-4alkyl-ORY, -C0-4alkyl-C(O)NRYRZ-, -C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY, -C0-4alkyl-NRYCO2RY, -C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4alkyl-NRWSO2RY, 1,3-dihydrobenzoimidazol-2-on-1-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol- 5-yl, -C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY, -C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, , ,; ii) 5-7-member heterocyclic ring HetRC which has one additional heteroatom separated from the said bonded nitrogen atom by at least one carbon atom, where the said additional heteroatom is chosen from a group which consists of O, S(=O)2 and >NRM, where the said 5-7-member heterocyclic ring HetRC has 0 or 1 carbonyl group and is substituted with 0, 1 or 2 substitutes at identical or different substituted carbon atoms, where the said substitutes are chosen from a group which consists of -C(O)RY and RZ; iii) one of 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl is substituted at the carbon atom by 0 or 1 substitute such as -C0-4alkyl-RZ, -C0-4alkyl-CO2RY; and iv) one of benzimidazol-1-yl, 2,8-diazospiro[4.5]decan-1-on-8-yl, 4-{[(2-tert-butoxycarbonylaminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 4-{[(2-aminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 9-yl-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid, 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl, and where substitute HetRa is a 6-member heterocyclic ring, with a carbon atom at the bonding site and contains a >NRM group as a heteroatom, where the said heteroatom is separated from the said carbon atom at the bonding site with at least 1 additional carbon atom; Rk is chosen from a group which consists of H and -C1-4alkyl; RL is chosen from a group which consists of -CO2RS; RS is hydrogen; RM is chosen from a group which consists of RZ, -C(O)RY; RN is chosen from a group which consists of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3 and NO2; RQ is chosen from a group which consists of -CN, -C0-4alkyl-ORY, -C0-4alkyl-CO2RY, -C0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY; RW is chosen from a group which consists of RY; RX is chosen from a group which consists of -ORY, -NRYRZ, -C1-4alkyl and -C1-4alkyl-RAr; RY is chosen from a group which consists of H, C1-4alkyl, -C0-4alkyl-RAr and -C0-4alkyl-RAr', each of which is substituted with 1 or 2 RN substitutes; RZ is chosen from a group which consists of RY, -C1-2alkyl-CO2RY ; RAr is a radical with a carbon atom at the bonding position, where the said radical is chosen from a group which consists of phenyl, pyridyl and pyrazinyl, where each carbon atom with permissible valence in each of the said groups is independently substituted with at least 0, 1 or 2 RN or 0 or 1 RL; RAr' is a 5-6-member ring which has 1 or 2 heteroatoms, chosen from a group which consists of O, S, N and >NRY, and has 0 or 2 unsaturated bonds and 0 or 1 carbonyl group, where each member with permissible valence in each of the said rings is independently substituted with 0 or 1 or 2 RK; Description is given of inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), a composition which contains these inhibitions, and their use for inhibiting activity of the LTA4H enzyme, as well as for treating, preventing or suppressing inflammation and/or conditions which are associated with such inflammation. In the said formula (I): X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is chosen from a group which consists of CH2 and O, W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to a nitrogen atom; R4 is chosen from a group which consist of H, OCH3, CI, F, Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently chosen from different groups.

EFFECT: new compounds have useful biological activity.

43 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel organic compounds of formula where R1 denotes H; halogen; -C0-C7-alkyl-O-R3; -NR4R5; R2 denotes phenyl, substituted with one or two substitutes selected from a group consisting of C1-7alkyl, halogen-C1-7alkyl, C1-7alkoxy, halogen-C1-7alkoxy, phenoxy, halogen, C1-7alkylpiperazinyl-C1-7alkyl, C3-C8-cyclalkyl, C1-7alkylpiperidinyl-C1-7alkyl and C1-7alkylimidazolyl; R3 denotes H or phenyl-lower alkyl; R4 and R5 are independently selected from a group consisting of H; lower alkyl; lower alkoxy-carbonyl and amino; A, B and X are independently selected from C(R7) or N, provided that not more than one or A, B and X denotes N; R7 denotes H; R8 denotes hydrogen; n equals 0; Y denotes O; Z denotes C; W is absent; K denotes N or C, and either a) if K denotes C, the bond shown by a wavy line () is a double bond, Q is selected from O-N, S-N, O-CH and S-CH, where in each case, the left-hand O or S atom is bonded through a bond shown in formula I to K, the right-hand N or carbon (CH) atom is bonded to C through a bond shown by a dotted line () in formula I, provided that said bond, which is shown by the dotted line, is a double bond with C; and the bond shown by a thick line () is a single bond; or b) if K denotes N, the bond shown by a wavy line () is a single bond; Q denotes N=CH, where the left-hand N atom is bonded through a bond shown in formula I to K, the right-hand carbon (CH) atom is bonded to C through a bond shown by a dotted line () in formula I, provided that said bond, which is shown by a dotted line, is a single bond with C; and the bond shown by thick line () is a double bond; or salt thereof (preferably pharmaceutically acceptable salt). The invention also relates to a pharmaceutical composition, having inhibiting action on protein kinase, containing a compound of formula I or salt thereof in an effective amount and at least one pharmaceutically acceptable carrier material.

EFFECT: heterocyclic carboxamides as kinase inhibitors.

12 cl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), in which (i) R1 denotes C1-C6-alkyl or hydrogen; and R2 denotes hydrogen or a -R7, -Z-Y-R7, -Z-NR9R10, -Z-CO-NR9R10, -Z-NR9-C(O)O-R7 or -Z-C(O)-R7 group; and R3 denotes an undefined pair or C1-C6-alkyl; or (ii) R1 and R3 together with a nitrogen atom with which they are bonded form a 5-6-member heterocycloalkyl ring; and R2 denotes an undefined pair or a -R7 , -Z-Y-R7 group; or (iii) R1 and R2 together with a nitrogen atom with which they are bonded form a 6-member heterocycloalkyl ring, where said ring is substituted with a -Y-R7 group, and R3 denotes an undefined pair or C1-C6-alkyl; R4 and R5 are independently selected from a group consisting of phenyl, C3-C6-cycloalkyl; R6 denotes -OH, C1-C6-alkyl, C1-C6-alkoxy or a hydrogen atom; A denotes an oxygen or sulphur atom; X denotes a C1-C6-alkylene group; R7 denotes C1-C6-alkyl, phenyl, phenyl(C1-C6-alkyl)-, dihydrobenzofuran or pyridine, where any phenyl in group R7 can be optionally substituted with one or two groups independently selected from halogen, aminoacyl, C1-C6-alkoxycarbonyl, aminosulphonyl, C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, -COOH; and any pyridine in group R7 can be optionaly substituted with C1-C6-alkyl; R8 denotes C1-C6-alkyl or a hydrogen atom; Z denotes a C1-C10-alkylene or C2-C10-alkenylene group; Y denotes a bond or an oxygen atom; R9 and R10 independently denote a hydrogen atom, C1-C6-alkyl group, isoxazole or 8-hydroxy-1H-quinolin-2-one-(C1-C6-hydroxyalkyl); and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition having activity with respect to M3 muscarinic receptor; use of the compounds of formula (I) to produce a medicinal agent for treating and a method of treating diseases or conditions in which M3 muscarinic receptor activity is involved.

EFFECT: compounds of given formula have activity with respect to M3 muscarinic receptor.

26 cl, 8 dwg, 91 ex

7FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a combination of a co-drug (an auxiliary) and a compound o formula (IV) in which radicals and symbols have the values defined in cl. 1 of the patent claim, or salts, or tautomers, or N-oxides, or solvates of this compound; where the specified auxiliary is specified from a monoclonal antibody, an alkylating agent, a malignant growth agent, other cycline-dependent kinase (CDK) inhibitor and a hormone, a hormone agonist, a hormone antagonist or a hormone-modulating agent specified in cl. 1 of the patent claim. The offered combination is used for tumour cell growth inhibition.

EFFECT: invention also refers to a pharmaceutical composition based on the offered combination, application of the combination and its separate ingredients and methods of treating, preventing and relieving the cancer symptoms in a patient.

77 cl, 2 dwg, 8 tbl, 257 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an isoxazoline-substituted benzamide derivative of formula or salt thereof, where A1 denotes a carbon or nitrogen atom, A2 and A3 independently denote a carbon atom, G denotes a benzene ring, W denotes an oxygen or sulphur atom, X denotes a halogen atom or C1-C6alkyl, arbitrarily substituted with a radical R4, Y denotes a halogen atom, cyano, nitro, C1-C6alkyl, C1-C6alkyl arbitrarily substituted with radical R4, -OR5, -N(R7)R6, phenyl, D-41, when n equals 2, each Y can be identical or different from each other, R1 denotes -C(R1b)=NOR1a, M-5, -C(O)OR1c, -C(O)SR1c, -C(S)OR1c, -C(S)SR1c, -C(O)N(R1e)R1d, -C(S)N(R1e)R1d, -C(R1d)=NN(R1e)R1lf, phenyl, phehnyl substituted with (Z)p1, or D-3, D-8, D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59, R2 denotes C1-C6alkyl, -CH2R14a, E-5, C3-C6alkynyl, -C(O)R15, -C(O)OR15, -C(O)C(O)OR15 or -SR15, where, when R1 denotes -C(R1b)=NOR1a, M-5, or -C(R1b)=NN(R1e)R1f, R2 can denote a hydrogen atom, when R1 denotes -C(O)OR1c, -C(O)SR1c, -C(S)OR1c or -C(S)SR1c, R2 can denote hydrogen, when R denotes -C(O)N(R1e)R1d or -C(S)N(R1c)R1d, R2 can denote a hydrogen atom, when R1 denotes phenyl, phenyl substituted with (Z)p1, or D-3, D-8, -D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59 R2 can denote C1-C6halogenalkyl, C1-C6alkyl arbitrarily substituted with a radical R14a, C3-C6alkenyl, -C(O)NH2, -C(O)N(R16)R15, or R2 together with R1 can form =C(R2b)R2a, R3 denotes C1-C6alkyl arbitrarily substituted with radical R4, D-1, D-3, D-8, D-13-D-15, D-21, D-35, D-41, D-52-D-55, D-57-D-59 denote aromatic heterocyclic rings, m equals an integer from 2 to 3, n equals an integer from 0 to 2.

EFFECT: isoxazoline-substituted benzamide derivative and salt thereof are used in pest control, against harmful arthropods in agriculture and horticulture or in livestock farming and in the field of hygiene.

12 cl, 18 tbl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I, where R1 denotes H; R6, R7, R8, R9, R10 independently denote H, F, Cl, Br, CF3, OCH3, OCF3, OCHF2, SCH3, SCF3, phenyl, (C1-C6)-alkyl, O-(C1-C6)-alkyl or NR3R4, where the alkyl and phenyl can be substituted with R2 once or many times, and where any two residues from R6, R7, R8, R9, R10 in neighbouring positions of the phenyl ring can form a -CH=CH-CH-CH- residue together; m equal 0, 1, 2 or 3; X denotes -(CH2)2-; R2 denotes F, Cl, Br, CN, OCH3, OCF3, CH3, CF3, (C1-C6)-alkyl or O-(C1-C6)-alkyl, where the alkyl can be substituted once or many times with OH, F, Cl, Br or CN; R3, R4 independently denote H or (C1-C6)-alkyl; or physiologically acceptable salts thereof, provided that the compound 3-(2-o- tolylamino-benzoxazol-6-yl)-propionic acid is excluded. The invention also relates to use of compounds of formula (I) to prepare a medicinal agent which activates GPR40 receptors and use of said compounds to prepare a medicinal agent for lowering blood sugar level, for treating diabetes and for increasing insulin secretion.

EFFECT: compounds of formula I which activate GPR40 receptors are obtained.

6 cl, 2 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (1), where A1, A2, A3, A4, A5 ad A6 are independently selected from a group comprising CR3 and N; provided that the biggest one of A1, A2, A , A4, A5 and A6 denotes N; B1, B2 and B3 are independently selected from a group comprising CR2 and N; each R3 independently denotes H or C1-C6 alkyl; and R1, R2, R4, R5, W and n are as given in the description, or salts thereof which are suitable for use in agriculture. The invention also relates to compositions containing compounds of formula (1), and insect-pest control methods which involve contact between the pest or habitat thereof with a biologically effective amount of the compound or composition according to the present invention, as well as to methods of protecting seeds and animals from insects-pests.

EFFECT: high effectiveness of the obtained compounds in insect-pest control.

29 cl, 12 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of formula I: or salt thereof, where: y equals 0; R1 and R2 are taken together to form a 3-tetrahydrofuran ring; R9 is hydrogen; R10 is 5-oxazolyl; R11 is a methoxy-, ethoxy- or isopropoxy group; each V1 is independently selected from halogen, NO2, CN, OR12, OC(O)R13, OC(O)R12, OC(O)OR13, OC(O)OR12, OC(O)N(R13)2, OP(O)(OR13)2, SR13, SR12, S(O)R13, S(O)R12, SO2R13, SO2R12, SO2N(R13)2, SO2NR12R13, SO3R13, C(O)R12, C(O)OR12, C(O)R13, C(O)OR13, NC(O)C(O)R13, NC(O)C(O)R12, NC(O)C(O)OR13, NC(O)C(O)N(R13)2, C(O)N(R13)2, C(O)N(OR13)R13, C(O)N(OR13)R12, C(NOR13)R13, C(NOR13)R12, N(R13)2, NR13C(O)R12, NR13C(O)R13, NR13C(O)OR13, NR13C(O)OR12, NR13C(O)N(R13)2, NR13C(O)NR12R13, NR13SO2R13, NR13SO2R12, NR13SO2N(R13)2, NR13SO2NR12R13, N(OR13)R13, N(OR13)R12, P(O)(OR13)N(R13)2 and P(O)(OR13)2; where each R12 is a monocyclic or bicyclic ring system consisting of 5-6 members in each ring, where said ring system optionally contains up to 4 heteroatoms selected from N, O or S, and where CH2 lying next to said N, O or S can be substituted with C(O); and each R12 optionally contains up to 3 substitutes selected from R11; where each R13 is independently selected from H, (C1-C4)-straight or branched alkyl or (C2-C4)-straight or branched alkenyl; and where each R13 optionally contains a substitute which is R14; where R14 is a monocyclic or bicyclic ring system consisting of 5-6 members in each ring, where said ring system optionally contains up to 4 heteroatoms selected from N, O or S, and where CH2 lying next to said N, O or S can be substituted with C(O); and each R14 optionally contains up to 2 substitutes independently selected from H, (C1-C4)-straight or branched alkyl or (C2-C4)-straight or branched alkenyl, 1,2-methylenedioxy-, 1,2-ethylenedioxy group or (CH2)n-Z; where Z is selected from halogen, CN, NO2, CF3, OCF3, OH, S(C1-C4)alkyl, SO(C1-C4)alkyl, SO2(C1-C4)alkyl, NH2, NH(C1-C4)-alkyl, M((C1-C4)alkyl)2, COOH, C(O)O(C1-C4)alkyl or O(C1-C4)-alkyl; and where any carbon atom in any R13 is optionally substituted with O, S, SO, SO2, NH or N(C1-C4)alkyl; where said method includes a step for reacting a compound of formula II with a compound of formula III in a polar or nonpolar aprotic, virtually anhydrous solvent or mixture thereof, and optionally in an acceptable base selected from an organic base, inorganic base or a combination of an organic base and an inorganic base; and while heating the reaction mixture to temperature ranging from approximately 30°C to approximately 180°C for approximately 1 to 48 hours in a virtually inert atmosphere: where: LG is -OR16; where R16 is -(C1-C6)-straight or branched alkyl; -(C2-C6)-straight or branched alkenyl or alkynyl; or a monocyclic ring system consisting of 5-6 members in each ring, where said ring system optionally contains up to 3 heteroatoms selected from N, O or S, and each R16 optionally contains up to 5 substitutes independently selected from (C1-C4)-straight or branched alkyl, (C2-C4)-straight or branched alkenyl or (CH2)n-Z; n equals 0, 1, 2, 3 or 4; V1, y, Z, R1, R2, R9, R10 and R11 are as indicated above; and provided that R16 is not a halogen-substituted (C2-C3)-straight alkyl.

EFFECT: improved method.

19 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where: X is a nitrogen or carbon atom; Ar is phenyl or a heteroaromatic ring selected from pyrazolyl, furanyl, thiophenyl and isoxazolyl; R1 is hydrogen, halogen, CN or (C1-C4)alkyl; R2 is halogen or (C1-C3)alkoxy optionally fluorinated with 1-3 fluorine atoms; R3 and R5 independently denote hydrogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkenyl or hydroxymethyl; R4 is hydrogen, halogen, optionally fluorinated (C1-C4)alkoxy or aryl(C1-C4)alkoxy; R6 is hydrogen, optionally fluorinated (C1-C4)alkyl; each R7 independenlty denotes hydrogen, halogen, optionally fluorinated (C1-C4)alkyl or (C1-C4)alkoxy optionally fluorinated with 1-3 fluorine atoms; or pharmaceutically acceptable acid addition salts thereof. The invention also relates to use of compounds of formula (I) in a pharmaceutical composition and when preparing a medicinal agent meant for treatment, the aim of which is to change the secondary signal activity level after activation of glucocorticoid receptors.

EFFECT: compounds of formula I for changing the secondary signal activity level after activation of glucocorticoid receptors.

7 cl, 5 dwg, 49 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically acceptable salts thereof, which have receptor tyrosine kinase type I inhibiting properties and can be used in treating hyperproliferative disorders in mammals. In general formula

,

A is O or S; G is N; B is a 6-member aryl or 5-6-member heteroaryl ring containing a sulphur atom as a heteroatom; E is

, , , , , X is N or CH; D1, D2 and D3 independently denote N or CR19; D4 and D5 independently denote N or CR19 and D6 is O, S or NR20, where at least one of D4 and D5 is CR19; D7, D8, D9 and D10 independently denote N or CR19, where at least one of D7, D8, D9 and D10 is N; R1 is H or C1-C6 alkyl; each R2 independently denotes halogen, cyano, nitro etc, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, -SR18, -OR15, -C(O)R15, -C(O)OR15, -NR14C(O)OR18, -OC(O)R15, -NR14SO2R18, -SO2NR15R14, -NR14C(O)R15, -C(O)NR15R14, -NR15C(O)NR15R14, -NR13C(NCN)NR15R14, -NR15R14, C1-C12alkyl, C2-C12 alkenyl, alkynyl, saturated or partially unsaturated C3-C10cycloalkyl, C3-C10cycloalkyl-C1-C12alkyl, -S(O)p(C1-C6alkyl), -S(O)p(CR13R14)q-phenyl, phenyl, phenyl-C1-3-alkyl, 5-6-member heteroaryl, 5-6-member heteroaryl-C1-C3-alkyl, saturated or partially unsaturated 3-8-member heterocyclyl, 5-6-member heterocyclyl-C1-C3-alkyl, -O(CR13R14)q-phenyl, NR15(CR13R14)q-phenyl, O(CR13R14)q-(5-6-member heteroaryl), NR13(CR13R14)q-(5-6-member heteroaryl, -O(CR13R14)q-(3-8-member heterocyclyl) or -NR15(CR13R14)q-3-8-member heterocyclyl), each R3 denotes Z, where Z is selected from and , W is O or S; W2 is O or S;V is CR8R9, R8b is H or C1-C6alkyl; each of R6, R8, R8a and R9 independently denotes hydrogen, trifluoromethyl, C1-C12alkyl etc.

EFFECT: improved properties and high efficiency of using the compounds.

25 cl, 13 dwg, 1 tbl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to method of obtaining derivatives of 2-aryl(hetaryl)-1H-indoles of general formula I:

IndexR1R2IaClIbОСН3IcHIdHIeНIfClIgCl

which is characterised by the fact that derivatives of 4-(1H-indol-3-yl)-but-3-en-2-ons II and phenylhydrazine hydrochloride are boiled in dimethylformamide for 2 min. Method ensures obtaining target products with output to 83%.

EFFECT: compounds can be used for synthesis of novel preparations of pharmaceutical purpose.

2 tbl, 10 ex

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