Derived arylpyrimidine, the methods of its production and pharmaceutical composition

 

The invention relates to new derivatives of arylpiperazines General formula I, where X Is O or S1- C1-C4alkoxy, CF3, R2- C1-C6alkyl, saturated With3-C6cycloalkyl; heteroseksualci of 3-6 ring atoms, heteroatom of which is O, S or N, optionally N-substituted With1-C6by alkyl; phenyl, optionally substituted by F, Cl, Br, NH2CH3CF3or OCH3; 5-6-membered heteroaryl, the heteroatom of which is O, S or N, possibly substituted, or condensed heteroaromatic system containing 9 atoms. The compounds I are active in the Central nervous system and is suitable for the treatment of sleep disorders, neurodegenerative diseases. 5 C. and 10 C.p. f-crystals, 6 tab., 1 Il.

Description text in facsimile form (see graphic part). T

Claims

1. Derived arylpyrimidine General formula Iwhere X represents an oxygen atom or sulfur; R1is1-C4alkoxy or triptorelin radical; R2is1-CRotom of which is oxygen, sulfur or nitrogen, optionally N-substituted With1-C6by alkyl; phenyl, optionally substituted by a Deputy selected from fluorine, chlorine, bromine, amino, methyl, trifloromethyl or methoxy; heteroaryl consisting of 5 - or 6-membered heteroaromatic ring heteroatoms selected from oxygen, sulphur or nitrogen, optionally substituted by substituents selected from chlorine, fluorine, methyl or methoxy; or heteroaryl consisting of condensed heteroaromatic systems, optionally substituted and containing 9 atoms, one of which is a heteroatom selected from sulfur or nitrogen, and the Deputy is a chlorine atom; heteroallyl, consisting of C1-C3alkyl groups and substituted 5-6-membered heteroaromatic ring, possibly substituted by a chlorine atom or a condensed 9-membered heteroaromatic system with 1-2 heteroatoms selected from sulfur or nitrogen, or its physiologically acceptable salt.

2. Connection on p. 1, where R1represents methoxy or ethoxy.

3. Connection on p. 1, where R2represents methyl.

4. Connection on p. 1, where R2is cyclopropyl or cyclohexyl.

5. Connection on p. 1, where R2of t is l, 3-chlorophenyl, 4-chlorophenyl, 2-AMINOPHENYL, 2-were, 2-(trifluoromethyl)phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl.

7. Connection on p. 1, where R2represents 2-furyl, 2-thienyl, 3-thienyl, 3-methyl-2-thienyl, 3-chloro-2-thienyl, 5-chloro-2-thienyl, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-indolyl, 2-benzo[b] thienyl, pyrazolyl, imidazolyl, thiazolyl.

8. Connection on p. 1, where R2is 2-thienylmethyl, 2-benzo[b]thienylmethyl.

9. Connection on p. 1, selected from the following group: 2-[4-(2-fullcarbon)-1-piperazinil]-4-methoxypyridine, hydrochloride 2-[4-(2-fullcarbon)-1-piperazinil]-4-methoxypyridine, 4-methoxy-2-[4-(2-thienylboronic)-1-piperazinil]pyrimidine,
hydrochloride 4-methoxy-2-[4-(2-thienylboronic)-1-piperazinil] pyrimidine,
2-(4-acetyl-1-piperazinil)-4-methoxypyridine,
2-{4-[4-(4-chloropyrazole)butanoyl]-1-piperazinil}-4-methoxypyridine,
hydrochloride 2-{4-[4-(4-chloropyrazole)butanoyl]-1-piperazinil}-4-methoxypyridine,
2-(4-benzoyl-1-piperazinil)-4-methoxypyridine,
2-(4-cyclopropanecarbonyl-1-piperazinil)-4-methoxypyridine,
2-[4-(2-fullcarbon)-1-piperazinil]-4-(trifluoromethyl)pyrimidine,
2-[4-(2-thienylboronic)-1-piperazinil]-4-(trifluoromethyl) pyrimidine,
4-methoxy-2-[4-(3-thienylboronic)-1-Pipeliner)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(5-methyl-2-thienylboronic)-1-piperazinil] -4-methoxypyridine,
4-methoxy-2-[4-(3-methoxy-2-thienylboronic)-1-piperazinil] pyrimidine,
hydrochloride 4-methoxy-2-[4-(3-methoxy-2-thienylboronic)-1-piperazinil] pyrimidine,
2-[4-(2-benzo[b]thienylboronic)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(2-benzo[b] thienylboronic)-1-piperazinil] 4-methoxypyridine,
2-[4-(2-indolocarbazole)-1-piperazinil]-4-methoxypyridine,
2-[4-(3-chloro-2-benzo[b]thienylboronic)-1-piperazinil]-methoxypyridine,
hydrochloride of 2-[4-(3-chloro-2-benzo[b]thienylboronic)-1-piperazinil]-4-methoxypyridine,
4-methoxy-2-[4-(2-pyrrolidinone)-1-piperazinil]pyrimidine,
hydrochloride 4-methoxy-2-[4-(2-pyrrolidinone]-1-piperazinil)pyrimidine
4-methoxy-2-[4-(2-titilate)-1-piperazinil]pyrimidine,
hydrochloride 4-methoxy-2-[4-(2-titilate)-1-piperazinil] pyrimidine,
2-[4-(3-methyl-2-thienylboronic)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(3-methyl-2-thienylboronic)-1-piperazinil] -4-methoxypyridine,
2-[4-(3-chloro-2-thienylboronic)-1-piperazinil]-4-methoxy-pyrimidine,
hydrochloride of 2-[4-(3-chloro-2-thienylboronic)-1-piperazinil] 4-methoxypyridine,
2-[4-(3-indolocarbazole)-1-piperazinil]-4-methoxypyridine,
2-[4-(3-benzo is Dean,
hydrochloride of 2-[4-(5-chloro-2-thienylboronic)-1-piperazinil] 4-methoxypyridine,
4-methoxy-2-[4-(4-chlorobenzoyl)-1-piperazinil]-4-methoxypyridine,
hydrochloride 4-methoxy-2-[4-(4-chlorobenzoyl)-1-piperazinil] 4-methoxypyridine,
2-[4-(4-perbenzoic)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(4-perbenzoic)-1-piperazinil]-4-methoxypyridine,
2-[4-(4-chlorobenzoyl)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(4-chlorobenzoyl)-1-piperazinil]-4-methoxypyridine,
4-methoxy-2-[4-(3-labels-Dibenzoyl)-1-piperazinil] pyrimidine,
hydrochloride 4-methoxy-2-[4-(3-methoxybenzoyl)-1-piperazinil] pyrimidine,
2-[4-(3-perbenzoic)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(3-perbenzoic)-1-piperazinil]-4-methoxypyridine,
2-[4-(3-chlorobenzoyl)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(3-chlorobenzoyl)-1-piperazinil]-4-methoxypyridine,
4-methoxy-2-[4-(2-methoxybenzoyl)-1-piperazinil]pyrimidine,
hydrochloride 4-methoxy-2-[4-(2-methoxybenzoyl)-1-piperazinil]pyrimidine,
2-[4-(2-(tormentil)-1-piperazinil]-4-methoxylamine,
hydrochloride of 2-[4-(2-(tormentil)-1-piperazinil]-4-methoxypyridine,
2-[4-(2-(chlorobenzoyl)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(2-(chlorobenzoyl)-1-piperazinil]-4-marks the 1-piperazinil)pyrimidine,
hydrochloride 4-methoxy-2-[4-(2-tetrahydrofuranyl)-1-piperazinil]pyrimidine,
hydrochloride 4-methoxy-2-(4-thiobenzoyl-1-piperazinil)pyrimidine,
2-(4-benzoyl-1-piperazinil)-4-methoxypyridine,
4-methoxy-2-{4-[4-(trifluoromethyl)benzoyl]-1-piperazinil)pyrimidine,
hydrochloride 4-methoxy-2-{4-[4-(trifluoromethyl)benzoyl]-1-piperazinil}pyrimidine,
4-methoxy-2-{4-[3-(trifluoromethyl)benzoyl]-1-piperazinil} pyrimidine,
hydrochloride 4-methoxy-2-{4-[3-(trifluoromethyl)benzoyl]-1-piperazinil}pyrimidine,
4-methoxy-2-{4-[2-(trifluoromethyl)benzoyl]-1-piperazinil} pyrimidine,
hydrochloride 4-methoxy-2-{4-[2-(trifluoromethyl)benzoyl]-1-piperazinil}pyrimidine,
4-methoxy-2-(4-nicotinoyl-1-piperazinil)pyrimidine,
dichlorhydrate 4-methoxy-2-(4-nicotinoyl-1-piperazinil)pyrimidine,
2-(4-isonicotinoyl-1-piperazinil)-4-methoxypyridine,
dichlorhydrate 2-(4-isonicotinoyl-1-piperazinil)-4-methoxypyridine,
2-[4-(1-imidazolidinyl)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(1-imidazolidinyl)-1-piperazinil] -4-methoxypyridine,
2-(4-nicotinoyl-1-piperazinil)-4-(trifluoromethyl)pyrimidine,
hydrochloride of 2-(4-nicotinoyl-1-piperazinil)-4-(trifluoromethyl)pyrimidine,
4-methoxy-2-[4-(2-pyridylcarbonyl)-1-piperazinil]pyrimidine,
chloroimide,
hydrochloride 4-ethoxy-2-[4-(2-thienylboronic)-1-piperazinil]pyrimidine,
2-[4-(3-chloro-2-thienylboronic)-1-piperazinil]-4-ethoxypyridine,
hydrochloride of 2-[4-(3-chloro-2-thienylboronic)-1-piperazinil] -4-ethoxypyridine,
4 ethoxy-2-{4-[2-(trifluoromethyl)benzoyl]-1-piperazinil}pyrimidine,
hydrochloride 4-ethoxy-2-{ 4-[2-(trifluoromethyl)benzoyl]-1-piperazinil}pyrimidine,
2-[4-(2-methylbenzoyl)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(2-methylbenzoyl)-1-piperazinil]-4-methoxypyridine,
2-[4-(4-perbenzoic)-1-piperazinil]-4-isopropoxypyridine,
hydrochloride of 2-[4-(4-perbenzoic)-1-piperazinil]-4-isopropoxypyridine,
4 isopropoxy-2-{4-[2-(trifluoromethyl)benzoyl]-1-piperazinil}pyrimidine,
hydrochloride 4-isopropoxy-2-(4-[2-(trifluoromethyl)benzoyl] -1-piperazinil} pyrimidine,
2-[4-(3-chloro-2-tinkerbel)-1-piperazinil]-4-isopropoxypyridine,
hydrochloride of 2-[4-(3-chloro-2-tinkerbel)-1-piperazinil] -4-isopropoxypyridine,
2-[4-(cyclohexylcarbonyl)-1-piperazinil]-4-methoxypyridazine
hydrochloride of 2-[4-(cyclohexylcarbonyl)-1-piperazinil] -4-methoxypyridine,
4 ethoxy-2-[4-(4-perbenzoic)-1-piperazinil]pyrimidine,
hydrochloride 4-ethoxy-2-[4-(4-perbenzoic)-1-piperazinil] pyrimidine,
2-[4-(2-thiazolidinone) -1-piperazinyl)-1-piperazinil]-4-methoxypyridine,
2-[4-(3-fluoro-2-thienylboronic)-1-piperazinil]-4-methoxypyridine,
hydrochloride of 2-[4-(3-fluoro-2-thienylboronic)-1-piperazinil]-4-methoxypyridine,
2-[4-(4-methoxy-2-pyrimidinyl)-1-piperazinylcarbonyl]benzoic acid,
2-[4-(2-acetoxybenzoic)-1-piperazinil]-4-methoxypyridine,
2-[4-(2-hydroxybenzoyl)-1-piperazinil]-4-methoxypyridine,
2-[4-(4-methoxy-2-pyrimidinyl) -1-piperazinylcarbonyl] sodium benzoate,
hydrochlorot 2-[4-(2-hydroxybenzoyl)-1-piperazinil]-4-methoxypyridine,
4-methoxy-2-[4-(2-methoxybenzoyl)-1-piperazinil]-4-methoxypyridazine and
4 ethoxy-2-[4- (2-pyridylcarbonyl)-1-piperazinil]pyrimidine.

10. The method of obtaining compounds of General formula I on p. 1, characterized in that the derived chloropyrimidine General formula III

where R1matter specified in paragraph 1,
subjected to interaction with piperazine derivatives of General formula IV

where R2matter specified in paragraph 1;
X represents an oxygen atom,
and if necessary, the resulting compound of formula I, where X represents the oxygen atom, is subjected to the action of the reagent Laussane (2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiophosphate-2,4-disulfide) or pentasulfide compounds of General formula I is transformed into its physiologically acceptable salt by reaction with a mineral acid in a suitable solvent.

11. The method of obtaining compounds of General formula I on p. 1, wherein interact amine of General formula V

where R1matter specified in paragraph 1,
with a carboxylic acid of General formula
R2COOH VI
or with a salt of the specified acid,
where R2matter specified in paragraph 1,
and if necessary, the resulting compound of General formula I, where X represents an oxygen atom, transform the action of the reagent Laussane (2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiophosphate-2,4-disulfide) or pentasulfide phosphorus compound of General formula I, where X represents a sulfur atom, and optionally any of the obtained compounds of General formula I is transformed into its physiologically acceptable salt by reaction with a mineral acid in a suitable solvent.

12. The method of obtaining compounds of General formula I on p. 1, wherein interact amine of General formula (V)

where R1matter specified in paragraph 1,
with a reagent of General formula
R2SDA, (VII),
where R2matter specified in paragraph 1;
Y represents a halogen atom, 1-imidazolidinyl group,
and if necessary, PROXIFIER)-1,3,2,4-dithiophosphate-2,4-disulfide) or pentasulfide phosphorus is converted into a compound of General formula I, where X represents a sulfur atom, and optionally any of the obtained compounds of General formula I is transformed into its physiologically acceptable salt of a mineral acid in a suitable solvent.

13. The pharmaceutical composition active against the Central nervous system of mammals, including humans, characterized in that it contains as active ingredient an effective amount of at least one of the compounds of General formula I or one of its physiologically acceptable salts according to any one of paragraphs.1-10, the combination of a pharmaceutically acceptable filler.

14. The compound of General formula I or its pharmaceutically acceptable salt according to any one of paragraphs.1-10 for the manufacture of drugs active in the Central nervous system of mammals, including humans.

15. The compound of General formula I or its pharmaceutically acceptable salt according to any one of paragraphs.1-10 for the manufacture of drugs with sedative, anticonvulsant, analgesic, anaesthetic, miorelaksantnoe and inducing sleep activity for the manufacture of a medicinal product for the treatment of sleep disorders, neurodegenerative diseases, disorders poznavat the ESA.

 

Same patents:

Arylalkylamine // 2201923
The invention relates to arylalkylamines formula I, where B - A, OA, NH2, CF3, aromatic heterocycle selected from pyridine, pyrazine and pyrimidine; Q is absent or denotes alkylene with 1-6 carbon atoms; R1and R2independently from each other represent OR5where R5- Or cycloalkyl with 3-7 carbon atoms; And the alkyl with 1-10 carbon atoms, and their physiologically acceptable salts

The invention relates to the derivatives of hintline formula I, where m is an integer from 1 to 2; R1represents hydrogen, nitro or1-3alkoxy; R2represents hydrogen or nitro; R3represents hydroxy, halogen, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy or cyano; X1represents-O-, -S-, -SO - or-SO2-; R4is one of 13 groups described in paragraph 1 of the claims

The invention relates to the derivatives of hintline formula I in which Z denotes-O-, -NH - or-S-; m = 1-5, integer, provided that when Z represents-NH-, m = 3 - 5; R1is hydrogen, C1-3alkoxy; R2is hydrogen; R3hydroxy, halogen, C1-3alkyl, C1-3-alkoxy, C1-3alkanoyloxy, trifluoromethyl or cyano; X1denotes-O-, -NR7, -NR8CO-, where R7and R8each is hydrogen, C1-3alkyl; R4choose one of the listed in paragraph 1 of the claims of the seven groups, except 4-(3,4,5-trimethoxyphenyl)-6,7-dimethoxyquinazoline, 4-(3-methoxybenzylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenylthio)-6,7-dimethoxyquinazoline, 4-(3-chlorophenoxy)-6,7-dimethoxyquinazolin and 4-(3,4,5-trimethoxyaniline)-6,7-dimethoxyquinazolin, or their salts

The invention relates to substituted 1-phenylpyrazol-3-carboxamide formula (Ia) in which R1xis in position 4 or 5 and denotes the group-T-CONRaRbin which T represents a direct bond or (C1-C7-alkylen; NRaRbdenotes a group selected from (a), (b), (C); R5and R6denote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8)-alkenyl or R5and R6together with the nitrogen atom to which they are linked, represent a heterocycle selected from pyrrolidine, piperidine, research, piperazine, substituted in position 4 by Deputy R9; R7denotes hydrogen, (C1-C4)-alkyl or benzyl; R8denotes hydrogen, (C1-C4)-alkyl, or R7and R8together with the carbon atom to which they are attached, form a (C3-C5-cycloalkyl; R9denotes hydrogen, (C1-C4)-alkyl, benzyl or a group-X-NR'5R'6in which R'5and R'6represent, independently from each other, (C1-C6)-alkyl; R10denotes hydrogen, (C1-C4)-alkyl; s= 0-3; t=0-3, provided that (s+t) in the same group greater than or equal to 1; the divalent radicals a and E together with the atom is which in addition, may be substituted by one or more (C1-C4-alkilani; R2xand R3xdenote, independently of one another, hydrogen, (C1-C6)-alkyl, (C3-C8-cycloalkyl, (C3-C8-cyclooctylmethyl provided that R2xand R3xdo not simultaneously denote hydrogen or R2xand R3xtogether form tetramethylene group; and their pharmaceutically acceptable salts

The invention relates to the derivatives of hintline formula (I), where Y1represents-O-, -S-, -NR5CO-, where R5is hydrogen; R1represents hydrogen or C1-3alkoxy; R2represents hydrogen; m is an integer from 1 to 5; R3represents hydroxy, halogen, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl or cyano; R4is one of five groups, which is optionally substituted by Spiridonova, phenyl or aromatic heterocyclic group with 1-3 heteroatoms selected from O, N and S, or contains such a group; and their salts, to processes for their preparation and to pharmaceutical compositions containing a compound of the formula (I) or its pharmaceutically acceptable salt as an active ingredient

The invention relates to sulphonilecarbomide acids of the formula

< / BR>
and/or their stereoisomeric forms and/or physiologically acceptable salts, where R1means phenyl, phenyl, one or twice substituted by a group WITH1-C6-alkyl-Oh, halogen, trifluoromethyl, a group WITH1-C6-alkyl-O-C(O)-, methylenedioxy-, R4-(R5)N-; triazole, thiophene, pyridine; R2means H, C1-C6alkyl; R4and R5are adnikowymi or different and denote H, C1-C6-alkyl; R3means H, C1-C10-alkyl, where alkyl unsubstituted and/or one hydrogen atom of the alkyl residue substituted by hydroxyl,2-C10alkenyl, R2-S(O)n-C1-C6-alkyl, where n means 0, 1, 2; R2-S(O)(=NH)-(C1-C6)-alkyl and the other, or R2and R3together form a cycle with a carboxyl group as a substituent cycle of partial formula II:

< / BR>
where r is 0, 1, 2, 3 and/or one of the carbon atoms in the cycle replaced by-O-, and/or the carbon atom in the cycle part of the formula II substituted once by phenyl; a represents a covalent bond, -O-;

The invention relates to acylaminocinnamic derivative of the formula (I), where R denotes phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, R1is hydrogen, alkyl, R2is hydrogen, alkyl or phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, R3is phenyl which is not substituted or may be substituted with halogen, alkyl, trifluoromethyl, hydroxy and alkoxygroup, or represents naphthyl, lH-indol-3-yl or 1-alcheringa-3-yl, R4' and R4"is hydrogen, alkyl, and one of the radicals R4' and R4"is hydrogen, and R5- cycloalkyl, D-azacycloheptan-2-he-3-yl or L-azacycloheptan-2-he-3-yl, or its salt

The invention relates to new arylpyrimidines compounds of formula I having the effect of antagonist 5HT2B-receptor, and pharmaceutical compositions

The invention relates to a new method of production (its variants) aminophenylalanine formula I, having the properties of plant growth regulators or herbicides, as well as intermediate products for their production

The invention relates to novel acylated to aminophenylacetylene General formula I which possess herbicide action and selectivity of action in comparison with the previously known compounds of this series

The invention relates to new substituted pyrimidinediamine or alkylating compounds, their pharmaceutically acceptable salts, hydrates, N-oxides and method for inhibition of reverse transcriptase of the virus

The invention relates to the technical field of herbicides and plant growth regulators, in particular of herbicides for selective control of weeds in cultivated plants

The invention relates to heterocyclic compounds having angiotensin II antagonistic activity

The invention relates to a method for producing 5-[3(4)-R-1-substituted]pyrimidines of General formula:

< / BR>
where R1, R2= H, lower alkyl, phenyl, substituted SN3, CF3, Cl-group; R3, R4, R5= N, hydroxyalkyl - or amino-group;

which can find wide application in the synthesis of biological active substances in medicine

The invention relates to the field of chemistry and technology of heterocyclic compounds, in particular 2,4,6-triamino-5-nitrosopyrimidine (TAP), which is used as intermediate in obtaining triamterena [1]

The number of known ways to get TARP, which can be divided into two groups

The invention relates to new arylpyrimidines compounds of formula I having the effect of antagonist 5HT2B-receptor, and pharmaceutical compositions
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