2-amino-4-phenylazoline derivatives and use thereof as hsp90 modulators

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I, which are HSP90 (heat-shock proteins) inhibitors and can be used to prepare a medicinal agent for treating tumorous diseases affected by HSP90 inhibition. In formula I R1 denotes Hal, H, OA or A, R2, R3 each independently denotes -O-(X)s-Q, -NHCO-(X)s-Q, -CONH-(X)s-Q, -NH(CO)NH-(X)s-Q, -NH(CO)O-(X)s-Q, -NHSOr(X)s-Q, NHCOA, Hal, Het or H, where, if R2=H, then R3≠H, or if R3=H, then R2≠H, R4 denotes H, R5 denotes H, Hal, A, OA, (CH2)nCOOH, (CH2)nCOOA, O(CH2)oCONH2, NHCOOA, NHCO(CH2)nNH2, NHCONHA or O(CH2)oHet1, A denotes a straight or branched alkyl containing 1-10 carbon atoms, in which 1-5 hydrogen atoms may be substituted with F, Cl and/or Br, X denotes a straight or branched C1-C10 alkylene which is unsubstituted or substituted once, twice or thrice by A, O A, OH, Hal, CN, COOH, COOA, CONH2, NH2, NHCOA, NHCOOA, Q denotes H, Ar or Het, Ar denotes phenyl which is unsubstituted or substituted once, twice or thrice with A, OA, OH, NO2, Hal, CN, (CH2)nCOOH, (CH2)nCOOA and/or tetrazole, Het denotes a cyclic saturated or aromatic 5-6-member heterocycle containing 1-2 N and/or O atoms, optionally condensed with a benzene ring which may be substituted once, twice or thrice with A, OA, OH and/or =O (carbonyl oxygen), Het1 denotes a monocyclic saturated, unsaturated or aromatic heterocycle containing 1-2 N and/or O atoms, which may be mono- or disubstituted with A, OA, OH, Hal and/or =O (carbonyl oxygen), Hal denotes F, Cl, Br or I, n equals , 1, 2, 3 or 4, o equals 1, 2 or 3, s equals 0, 1 or 2.

EFFECT: high efficiency of using said derivatives.

4 cl, 4 dwg, 1 tbl, 29 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula I

in which R1represents Hal, N, OA, or And,
R2, R3each independently from each other represents-O-(X)s-Q, -NHCO-(X)s-Q, -CONH-(X)s-Q, -NH(CO)NH-(X)s-Q, -NH(CO)O-(X)s-Q, -NHSO2(X)s-Q, NHCOA, Hal, Het or N,
where, if R2=H, R3≠N, or
if R3=H, R2≠H,
R4represents H,
R5is the Wallpaper H Hal, A, OA, (CH2)nCOOH, (CH2)nCooa, O(CH2)oCONH2, NHCOOA, NHCO(CH2)nNH2, NHCONHA or O(CH2)oHet1,
And represents an unbranched or branched alkyl containing 1-10 carbon atoms, in which 1-5 h atoms may be replaced by F, Cl and/or Br,
X represents an unbranched or branched C1-C10alkylene, unsubstituted or one, two or three times substituted by A, OA, HE, Hal, CN, COOH, cooa, CONH2, NH2, NHCOA, NHCOOA,
Q represents H, AG or Het,
AG represents a phenyl, unsubstituted or one, two or three times substituted by A, OA, HE, NO2Hal, CN, (CH2)nCOOH, (CH2)nCooa and/or tetrazole,
Het represents a cyclic saturated or aromatic 5 to 6 membered heterocycle containing 1-2 atoms N and/or O, optionally condensed with a benzene ring, which may be one, two or three times substituted by A, OA, HE and/or=O (carbonyl oxygen),
Het1represents a monocyclic saturated, unsaturated or aromatic heterocycle containing 1-2 atoms N and/or O, which may be single - or Duhalde A, OA, HE, Hal and/or=O (carbonyl oxygen),
Hal represents F, Cl, Br or I,
n represents 0, 1, 2, 3,or 4
o represents 1, 2 or 3,
s submitted is a 0, 1 or 2
and their pharmaceutically usable salts and stereoisomers,
provided that if s=0, then Q does not mean hydrogen.

2. Compounds according to claim 1, selected from the group including
2-amino-6-chloro-4-[3-(3-methoxycarbonylpropionyl)phenyl]hinzelin ("A1"),
2-amino-6-chloro-4-[3-(3-aminocarbonylmethyl)phenyl]hinzelin ("A3"),
2-amino-6-chloro-4-[2-(indazol-7-ylcarbonyl)phenyl]hinzelin ("AA"),
2-amino-6-chloro-4-[2-(2-hydroxypyridine-4-ylcarbonyl)phenyl]hinzelin ("AA"),
2-amino-6-chloro-4-[3-(3-aminodiphenylamine)phenyl]hinzelin ("A13"),
2-amino-6-chloro-4-[3-(4-aminoethylamino)phenyl]hinzelin ("A15"),
(S)-2-amino-6-chloro-4-[3-(2-aminodiphenylamine)phenyl]hinzelin ("A25"),
(R)-2-amino-6-chloro-4-[3-(2-aminodiphenylamine)phenyl]hinzelin ("A27"),
(S)-2-amino-6-chloro-4-[3-(2-amino-3-hydroxypropylamino)phenyl]hinzelin ("A33"),
(R)-2-amino-6-chloro-4-[3-(2-amino-3-hydroxypropylamino)phenyl]hinzelin ("AA"),
(2S)-2-amino-6-chloro-4-[3-(2-amino-3-hydroxyethylamino)phenyl]hinzelin ("A35"),
(2R)-2-amino-6-chloro-4-[3-(2-amino-3-hydroxyethylamino)phenyl]hinzelin ("AA"),
(S)-2-amino-6-chloro-4-[3-(2-amino-3-aminocarbonylmethyl)phenyl]hinzelin ("A37"),
(R)-2-amino-6-chloro-4-[3-(2-amino-3-aminocarbonylmethyl)phenyl]hinzelin ("A39"),
(R)-2-amino-6-chloro-4-[3-(2-amino-3-(1H-imidazol-4-yl)propionamido)phenyl]hinzelin ("A41"),
2-amino-6-chloro-4-[5-fluoro-4-methoxy-2-benzoylamino the phenyl]hinzelin ("A44"),
2-amino-6-chloro-4-(4-chloro-3-{2-[(tert-butyloxycarbonyl)amino]-2-(1H-imidazol-4-yl)acetamido}phenyl)hinzelin ("A45"),
2-amino-6-chloro-4-{4-chloro-3-[2-amino-2-(1H-imidazol-4-yl)acetamido]phenyl}hinzelin ("A46"),
2-amino-6-chloro-4-{4-chloro-2-[2-amino-2-(1H-imidazol-4-yl)acetamido]phenyl}hinzelin ("A"),
4-{3-[3-(2-amino-7-methylpyrazole-4-yl)-5-chlorophenyl]ureido}benzoic acid ("A48 motorway"),
4-{3-[2-(2-amino-7-methylpyrazole-4-yl)-5-chlorophenyl]ureido}benzoic acid (A"),
2-amino-6-methoxy-4-[4-methoxy-3-(3-torpedoshaped)phenyl]hinzelin ("A50"),
2-amino-6-methoxy-4-[4-methoxy-2-(3-torpedoshaped)phenyl]hinzelin ("A51 motorway"),
2-amino-6-chloro-4-[3-(3-triftormetilfosfinov)phenyl]hinzelin ("A56"),
2-amino-6-chloro-4-[2-(3-triftormetilfosfinov)phenyl]hinzelin ("A57"),
2-amino-6-aminocarbonylmethyl-4-(4-methoxy-3-acetamidophenyl)hinzelin ("A52"),
2-amino-6-aminocarbonylmethyl-4-(4-methoxy-2-acetamidophenyl)hinzelin ("A53"),
2-amino-4-[4-ethoxy-3-(2-hydroxyethoxy)phenyl]-6-[2-(4-methylpiperazin-1-yl)ethoxy]hinzelin ("A54"),
2-amino-4-[4-ethoxy-2-(2-hydroxyethoxy)phenyl]-6-[2-(4-methylpiperazin-1-yl)ethoxy]hinzelin ("A55"),
2-amino-6-chloro-4-[3-(3-methoxycarbonylpropionyl)-4-methoxyphenyl]hinzelin,
2-amino-6-chloro-4-[3-(3-carboxypropyl)-4-methoxyphenyl]hinzelin ("A58 motorway"),
2-amino-6-chloro-4-[2-(3-carboxypropyl)-4-methoxyphenyl]hinzelin ("A59"),
2-amino-6-chloro-4-[3-(3-carboxypropyl)-5-methoxy who enyl]hinzelin ("A66"),
2-amino-6-chloro-4-[2-(3-carboxypropyl)-5-methoxyphenyl]hinzelin ("A67"),
2-amino-6-aminoethylethanolamine-4-[3-(3-aminocarbonylmethyl)phenyl]hinzelin ("A60"),
2-amino-6-aminoethylethanolamine-4-[2-(3-aminocarbonylmethyl)phenyl]hinzelin ("A61"),
2-amino-6-chloro-4-{3-[2-(tert-butyloxycarbonyl)ethoxy]phenyl}hinzelin,
2-amino-6-chloro-4-[3-(2-aminoethoxy)phenyl]hinzelin,
2-amino-6-chloro-4-(3-{2-[3-(2-forfinal)ureido]ethoxy}phenyl)quinoline ("A62"),
2-amino-7-methoxy-4-[3-(2-hydroxyethoxy)phenyl]hinzelin,
2-amino-7-methoxy-4-{3-[2-(2-carbamoylphenoxy)ethoxy]phenyl]hinzelin ("A63"),
methyl {[3-(2-aminoquinazolin-4-yl)-2,4-dichlorophenylamino]methoxy}acetate,
{[3-(2-aminoquinazolin-4-yl)-2,4-dichlorophenylamino]methoxy}acetic acid ("A"),
{[2-(2-aminoquinazolin-4-yl)-4-chlorpheniramol]methoxy}acetic acid ("A65"),
2-{2-[3-(2-amino-6-chlorination-4-yl)phenoxy]acetylamino}-3-phenylpropionate acid ("A68"),
2-{2-[2-(2-amino-6-chlorination-4-yl)-5,6-dichlorphenoxy]acetylamino}-3-phenylpropionate acid (A"),
2-amino-6-fluoro-4-[3-(4-methylpiperazin-1-yl)phenyl]hinzelin ("A70"),
2-amino-6-fluoro-4-[2-(4-methylpiperazin-1-yl)-6-forfinal]hinzelin ("A71"),
2-amino-6-fluoro-4-[3-(1H-indol-7-enaminocarbonyl)-4-methoxyphenyl]hinzelin ("A72"),
2-amino-6-fluoro-4-[2-(1H-indol-7-enaminocarbonyl)-4-methoxyphenyl]hinzelin ("A73 motorway"),
2-amino-6-chloro-4-[3-(2-methylbenzylamino)phenyl]Chinas the Lin ("A74"),
2-amino-6-chloro-4-[3-(3-methylbenzylamino)phenyl]hinzelin ("A75"),
2-amino-6-chloro-4-[3-(4-methylbenzylamino)phenyl]hinzelin ("A76"),
2-amino-6-chloro-4-[3-(2-forbindelse)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-forbindelse)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(4-forbindelse)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(2-chlorobenzoyloxy)phenyl]hinzelin ("A80"),
2-amino-6-chloro-4-[3-(3-chlorobenzoyloxy)phenyl]hinzelin ("A81"),
2-amino-6-chloro-4-[3-(4-chlorobenzoyloxy)phenyl]hinzelin ("A82"),
2-amino-6-chloro-4-[3-(2-triftormetilfosfinov)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(4-triftormetilfosfinov)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(4-methoxycarbonylbenzyl)phenyl]hinzelin ("A85"),
2-amino-6-chloro-4-[3-(3-methoxycarbonylbenzyl)phenyl]hinzelin ("A86"),
2-amino-6-chloro-4-[3-(3-cryptomaterial)phenyl]hinzelin ("87 Motorway"),
2-amino-6-chloro-4-[3-(4-cryptomaterial)phenyl]hinzelin ("A88"),
2-amino-6-chloro-4-[3-(3-nitrobenzyloxy)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(4-cyanobenzyl)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-cyanobenzyl)phenyl]hinzelin ("A"),
2-amino-4-[3-(3-triphtalocyaninine)phenyl]hinzelin ("A92"),
2-amino-6-chloro-4-[3-(3-carboxymethylamino)phenyl]hinzelin ("93"),
2-amino-6-chloro-4-[3-(4-carboxyphenoxy)phenyl]hinzelin ("A94"),
2-amino-6-chloro-4-[3-(3-carboxyphenoxy)phenyl]hinzelin ("A95"),
2-AMI is about-6-chloro-4-[3-(3-ethoxycarbonylmethoxy)-4-methoxyphenyl]hinzelin ("a"),
2-amino-6-chloro-4-[3-(2-forbindelse)-4-methoxyphenyl]hinzelin ("A99 motorway"),
2-amino-6-chloro-4-[3-(3-forbindelse)-4-methoxyphenyl]hinzelin ("A100"),
2-amino-6-chloro-4-[3-(4-forbindelse)-4-methoxyphenyl]hinzelin ("A101"),
2-amino-6-chloro-4-[3-(2-triftormetilfosfinov)-4-methoxyphenyl]hinzelin ("A102"),
2-amino-6-chloro-4-[3-(3-triftormetilfosfinov)-4-methoxyphenyl]hinzelin ("A103"),
2-amino-6-chloro-4-[3-(4-triftormetilfosfinov)-4-methoxyphenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-diversitybusiness)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-cryptomaterial)phenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(2-phenylethane)-4-methoxyphenyl]hinzelin ("A107"),
2-amino-6-chloro-4-[3-(3-methoxycarbonylbenzyl)-4-methoxyphenyl]hinzelin ("A108"),
2-amino-6-chloro-4-[3-(4-methoxycarbonylbenzyl)-4-methoxyphenyl]hinzelin ("a"),
2-amino-6-fluoro-4-[3-(1H-indol-7-enaminocarbonyl)phenyl]hinzelin ("A"),
sodium salt of 2-amino-6-chloro-4-[3-(3-carboxypropyl)-4-methoxyphenyl]hintline ("A111"),
sodium salt of 2-amino-6-chloro-4-[3-(3-carboxyphenoxy)-4-methoxyphenyl]hintline ("A112"),
sodium salt of 2-amino-6-chloro-4-[3-(4-carboxyphenoxy)-4-methoxyphenyl]hintline ("A113"),
2-amino-6-fluoro-4-[3-(1H-indazol-7-enaminocarbonyl)phenyl]hinzelin ("A"),
2-amino-6-fluoro-4-[3-(2-etoxycarbonyl-1H-indole-7-ylamino-carbonyl)phenyl]hinzelin ("A115"),
2-amino-6-chloro-4-[3-(4-cyanobenzyl)--methoxyphenyl]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-cyanobenzyl)-4-methoxyphenyl]hinzelin("A"),
2-amino-6-chloro-4-[3-(4-methoxycarbonylbenzyl)-4-were]hinzelin ("A120"),
2-amino-6-chloro-4-[3-(3-methoxycarbonylmethylene)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(4-cyanobenzylidene)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-cyanobenzylidene)-4-were]hinzelin ("a"),
2-amino-6-chloro-4-[3-(1-oxypyridine-4-ylcarbonyl)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(pyridine-4-ylcarbonyl)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(1-oxypyridine-3-ylcarbonyl)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(pyridine-3-ylcarbonyl)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-methoxycarbonylpropionyl)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-cyanopropyl)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(2-cyanoacetamide)-4-were]hinzelin ("A130"),
2-amino-6-chloro-4-[3-(Gex-5-anolamine)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(4-carboxymethylamino)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-[3-(3-carboxymethylamino)-4-were]hinzelin ("A"),
2-amino-6-chloro-4-(3,4-acid)hinzelin ("A"),
2-amino-6-methoxycarbonyl-4-(3,4-acid)hinzelin ("A"),
2-amino-6-chloro-4-{3-[3-(1H-tetrazol-5-yl)benzyloxy]-4-methoxyphenyl}hinzelin ("A"),
2-amino-7-the ENT-4-(3,4-acid)hinzelin ("A"),
2-amino-6-chloro-4-{3-[4-(1H-tetrazol-5-yl)benzyloxy]-4-methoxyphenyl} hinzelin ("A"),
(S)-2-amino-N-[3-(2-amino-6-chlorination-4-yl)phenyl]-3-cyanopropionic("A"),
(R)-2-amino-N-[3-(2-amino-6-chlorination-4-yl)phenyl]-3-cyanopropionic ("A140"),
2-amino-6-chloro-4-[3-(5-amino-pentyloxy)phenyl]hinzelin ("A141"),
and their pharmaceutically usable salts and stereoisomers.

3. Drugs having inhibitory activity against HSP90 containing an effective amount of at least one compound of formula I according to claim 1 and/or pharmaceutically usable salts and stereoisomers, and fillers and/or auxiliaries.

4. The use of compounds of the formula I and their pharmaceutically usable salts and stereoisomers according to claim 1 for the preparation of drugs for the treatment and/or prevention of diseases which are influenced by inhibition of HSP90.



 

Same patents:

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula , where R1 represents aryl, heteroaryl or (C5-C6)-cycloalkyl, each of which has an optional substitute halogen or (C1-C6)-alkyl; R2 represents hydrogen or (C1-C4)-alkyl; R3 represents -P(=O)-(alkoxy)2 or Y1Y2N-SO2-, cycloalkyl, aryl, heteroaryl, heterocyclyl, cycloalkenyl, each of which has an optional substitute: halogen, hydroxy, carboxy, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2N-SO2, R7-SO2-NR6-, R7-C(=O)-NR6-, or alkyl, alkoxy, alkoxycarbonyl, each of which has an optional substitute halogen, -P(=O)-(alkoxy)2, Y1Y2NC(=O)-, Y1Y2N-SO2-, R7 -SO2-NR6 -, aryl or heteroaryl and when R3 is cycloalkyl, cycloalkenyl, heterocyclyl, it also optionally substituted by oxo; L1 represents a bond or (C1-C6)-alkylene, which is optionally substituted by -P(=O)-(alkoxy)2; R4, R5 and R6 are hydrogen, R7 represents alkyl; both Y1 and Y2 independently is hydrogen, alkyl which has an optional substitute: hydroxy, amino, alkylamino, dialkylamino, alkoxy, cycloalkyl, or Y1 and Y2 together with nitrogen atom whereto attached form heterocyclyl which optionally contains one more heteroatoms selected from oxygen, nitrogen or sulphur where heterocyclyl has an optional substitute alkyl or oxo; provided when L1 represents a bond, R3 is not optionally substituted by phenyl, optionally substituted by naphthyl, optionally substituted by benzoimidazolyl, optionally substituted by benzothiazolyl or optionally substituted by tetrazolyl; or to its pharmaceutically acceptable salt, and also to a pharmaceutical composition including a compound of formula I.

EFFECT: there are produced and described new compounds which can be effective in treating allergic or inflammatory disorders, particularly such disorders, as allergic rhinitis, asthma or chronic obstructive pulmonary disease.

25 cl, 118 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

where there are R3/R3', R4/R4' and R5/R5' where at least one of either R4/R4' or R5/R5' always represents a fluorine atom, and the other radical values are disclosed in the description.

EFFECT: making the compounds which are γ-secretase inhibitors, and can be effective in treating Alzheimer's disease or advanced cancers, including but not limited to carcinoma of uterine cervix and breast carcinoma and malignant tumours of hematopoietic system.

15 cl, 3 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are novel azole compounds, which contain carbamoyl group, of general formula IX: where A stands for azole group of general structural formula or G stands for ring, selected from group, consisting of piperonyl, indanyl, naphtyl, possibly substituted phenyl, benzodioxole and phenoxymethyl, (values of radicals are given in the invention formula), their pharmaceutically acceptable salts and pharmaceutical compositions, containing them, which can be applied for treatment of various central nervous system disorders, especially such as anxiety, depression, convulsions, epilepsy, migraine, bipolar disorder, medication abuse, smoking, ADHD, obesity, sleep disorder, neurogenic pain, stroke, cognitive impairment, neurodegeneration and muscle spasm.

EFFECT: obtaining novel azole compounds and their pharmaceutically acceptable salts and pharmaceutical compositions, containing them, which can be applied for treatment of various central nervous system disorders.

71 cl, 3 tbl, 199 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of compounds, characterised by formulae (I) and (IB), or pharmaceutically acceptable salts thereof, isomers or hydrates to prepare a medicinal agent for treating or preventing diseases or conditions mediated by the sigma-receptor, selected from psychosis, neuropathic pain or inflammatory pain and movement disorder, such as dystonia or tardive dyskinesia, motor defects, including allodynia/or hyperalgesia. Radicals and symbols in compounds of formulae (I) and (IB) are described in claims 1 and 2. The invention also relates to novel compounds of formulae (I') and (IB'), in which radicals and symbols are described in claims 4 and 5, having pharmacological activity on the sigma-receptor, methods of producing such compounds, a pharmaceutical composition containing said compounds and use of said compounds in preparing a medicinal agent for treating and/or preventing diseases or conditions whose development involves the sigma-receptor. (I), (IB) (I') and (IB').

EFFECT: high effectiveness of the inhibitors.

22 cl, 1 tbl, 3 dwg, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (3-trifluromethylphenyl)amide 6-(6-hydroxymethylpyrimidin-4-yloxy)naphthalene-1-carboxylic acid or tautomer or salt thereof. The invention also relates to a pharmaceutical composition which has protein kinase inhibiting activity, based on the said compound and use of the said compound to prepare pharmaceutical compositions for use in treating protein kinase dependent diseases, preferably proliferative diseases, particularly tumorous diseases.

EFFECT: improved properties of compounds.

6 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I, where R1 -OH, R2- CONAA', SO2NAA', SO2NA-benzyl, SO2NHAr, SO2NAHet, SO2NHA or S(O)mHet, R3, R5, R6 - H, R4 - H, Hal or A, Y - OH, A, A' denotes a straight or branched C1-C10 alkyl, in which one CH2 group can be substituted with NR8, where R8 denotes a straight or branched C1-C6 alkyl or cycloalkyl, Ar denotes phenyl, Het denotes a saturated C5-C6-heterocyclic ring containing 1-2 nitrogen atoms, which can be substituted with A, m equals 1 or 2, and pharmaceutically suitable salts or tautomers thereof. The invention also relates to a method of producing said compounds and pharmaceutically suitable salts or tautomers thereof. The invention also relates to use of said compounds, salts or tautomers to prepare a medicinal agent for treating and/or preventing diseases affected by HSPS90 inhibition, as well as a medicinal agent based on said active ingredients, having HSP90 inhibiting activity. The invention also relates to an intermediate compound of formula I-1, where Z denotes A, Y - OH, R1 - OCH3, R2 - SO2Het, SO2NHAr or SO2NAA', R3 - H, R4 - Hal or A, R5, R6 - H, Ar - phenyl, Het - saturated C5-C6-heterocyclic ring, containing 1-2 nitrogen atoms which can be substituted with A, A, A' - straight or branched C1-C10 alkyl.

EFFECT: high efficiency of the composition.

6 cl, 1 tbl, 23 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: present invention presents new compounds which are modulators of cannabinoid receptors, particularly modulators of cannabinoid receptors 1 (CB1) or cannabinoid receptors 2 (CB2), and an application thereof for treating diseases, conditions and/or disorders regulated by a cannabinoid receptor (such as painful sensations, neurodegenerative disorders, ingestion disorders, weight loss or weight control and obesity), as well as based pharmaceutical compositions. New compounds are characterised by graphic formulas

in which radicals and groups have the values specified in the patent claim.

EFFECT: higher efficiency of applying the composition.

55 cl, 13 tbl, 3 dwg, 802 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described new macrocyclic compound of general formula 1-c:

and its pharmaceutically acceptable acid or base addition salts or its stereoisomers (the radical values are presented in the patent claim).

EFFECT: producing the compounds which are hepatitis type C virus inhibitors and can find application in medicine.

9 cl, 1 tbl, 95 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

where there are R3/R3', R4/R4' and R5/R5' where at least one of either R4/R4' or R5/R5' always represents a fluorine atom, and the other radical values are disclosed in the description.

EFFECT: making the compounds which are γ-secretase inhibitors, and can be effective in treating Alzheimer's disease or advanced cancers, including but not limited to carcinoma of uterine cervix and breast carcinoma and malignant tumours of hematopoietic system.

15 cl, 3 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula

where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula

in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.

EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.

39 cl, 7 tbl, 180 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of formula I in which cycle A represents unsaturated carbocycle with double bonds, which is selected from phenyl or naphtyl; 1 can take value from 1 to 3; m can take value 0, 2 or 3; n can take value 0 or 2; R1 represents a hydrogen atom, (C1-3)alkyl group; R2 represents(C1-6)alkyl group, which is possibly substituted with substituent, selected from C6-cycloalkyl, monocyclic heteroaryl, selected from thiophene, aryl group, selected from phenyl, in form of base or salt of bonding with an acid. Invention also relates to pharmaceutical composition, based on formula I compound, to application of formula I compound for obtaining medication, to method of obtaining formula I compound and to application of formula compound for obtaining formula 1 compound.

EFFECT: obtained are novel isoquinoline and benzo[h]isoquinoline derivatives, possessing properties of antagonists of histamine type H3 receptor.

9 cl, 1 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of compounds, characterised by formulae (I) and (IB), or pharmaceutically acceptable salts thereof, isomers or hydrates to prepare a medicinal agent for treating or preventing diseases or conditions mediated by the sigma-receptor, selected from psychosis, neuropathic pain or inflammatory pain and movement disorder, such as dystonia or tardive dyskinesia, motor defects, including allodynia/or hyperalgesia. Radicals and symbols in compounds of formulae (I) and (IB) are described in claims 1 and 2. The invention also relates to novel compounds of formulae (I') and (IB'), in which radicals and symbols are described in claims 4 and 5, having pharmacological activity on the sigma-receptor, methods of producing such compounds, a pharmaceutical composition containing said compounds and use of said compounds in preparing a medicinal agent for treating and/or preventing diseases or conditions whose development involves the sigma-receptor. (I), (IB) (I') and (IB').

EFFECT: high effectiveness of the inhibitors.

22 cl, 1 tbl, 3 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

wherein Q together with carbon and nitrogen atoms whereto attached forms a 5-6-members monocyclic heteroaromatic ring; or Q together with carbon and nitrogen atoms whereto attached forms a 9-10-members bicyclic heterocycle; R1 and R2 independently mean hydrogen, halogen, alkyl, alkyl substituted by one or more halogen, alkoxygroup, alkoxygroup substituted by alkoxygroup, alkylthiogroup, sulphonyl, free or etherified carboxygroup, carbamoyl, sulohamoyl, morpholinyl or pyridinyl; or R2 is absent; R3 means (C3-C6)cycloalkyl; R4 means hydrogen, halogen, lower alkyl or lowest alkyl substituted by one or more halogen; R5 means (C3-C6cycloalkyl, (C6-C10) aryl, (C3-C10)heterocyclyl or (C1-C6)alkyl optionally substituted by (C1-C6)alkoxygroup, (C3-C7)cycloalkyl, (C6-C10)aryl or (C3-C10)heterocyclyl; R6 means free or etherified carboxygroup; and n is an integer equal to 1-6; or to its enanthiomer, or a mixture of its enanthiomers, or its pharmaceutically acceptable salt. Besides, the invention refers to a method of glucokinase activation in mammals, to a method of treating pathological conditions associated with glucokinase activation in mammals and impaired glucose tolerance, as well as to a pharmaceutical composition based on these compounds and to application of said compositions for preparing a drug.

EFFECT: there are produced and described new compounds which are activators and can be used as therapeutic agents for treating the glucokinase mediated pathological conditions.

31 cl, 4 ex

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