Derivatives chromane, intermediate compounds, pharmaceutical composition and methods of treatment.

 

The invention relates to new derivatives chromane General formula I,where R means hydrogen, halide or NR1R1group; R1means hydrogen or alkyl group with 1-10 carbon atoms; R2means R1or NR1R1; R3means hydrogen or CO2R1; Ar1means a phenyl group or a 5-or 6-membered heterocyclic ring containing as the heteroatom atom N; m = 1, 2, or 3; n = 1, when this symbol is the group -(CO)nand n is 0, 1 or 2, when this symbol is the group (X); X is alkyl group with 1-4 carbon atoms; R4means hydroxyl or CNS group with 1-10 carbon atoms; and their pharmaceutically acceptable salts, having agonistic activity against beta-3-adrenergic receptor. The invention also relates to intermediate products for preparing compounds of formula I, pharmaceutical compositions based on compounds of the formula I and methods for treating diabetes and obesity. The technical result - the new derivatives chromane of valuable bioactive properties. 9 C. and 5 C.p. f-crystals, 3 tables.

Tex is Derived chromane General formula I

where R is hydrogen, halide or NR1R1group;

R1means hydrogen or alkyl group with 1-10 carbon atoms;

R2means R1or NR1R1;

R3means hydrogen or CO2R1;

Ar1means phenyl group or ili 6-membered heterocyclic ring containing as the heteroatom atom N;

m is 1, 2 or 3;

n is 1 when this symbol is the group -(CO)nand n is 0, 1 or 2 when this symbol is the group (X);

X means an alkyl group with 1-4 carbon atoms;

R4means hydroxyl or CNS group with 1-10 carbon atoms.

and their pharmaceutically acceptable salts.

2. Connection on p. 1, characterized in that AG1can contain as substituents of phenyl, pyridyloxy, pyramidalnou or pirronello group.

3. Connection on p. 2, wherein R3means hydrogen and m=1.

4. Connection on p. 3, characterized in that (X)n-(CO)nR4attached to Romanova segment in position 6 and n=0 for (X)n, a (CO)nR4is the CO2R1.

5. Connection on p. 1, characterized in that the _data/72/728827.gif">

where R3, R4, X, m and n have the above meaning,

as an intermediate product to obtain the compounds of formula I.

7. Connection on p. 6, characterized in that (X)n-(CO)nR4attached to Romanova segment in position 6 and n=0 for (X)n, a (CO)nR4means CO2R1.

8. Method of providing agonistic effects on beta-3-adrenergic receptor in need of such effects to the patient by introducing effective from the pharmaceutical point of view the number of connections on p. 1.

9. Pharmaceutical composition having agonistic activity against beta-3-adrenergic receptor containing an effective amount of the compounds under item 1 in combination with a pharmaceutically acceptable carrier.

10. The composition having agonistic activity against beta-3-adrenergic receptor containing an effective amount of the compounds under item 1 in combination with an inert carrier.

11. A method of treating obesity in a mammal, which consists in the introduction in need of such treatment, the patient is effective from the pharmaceutical point of view the number of connections on p. 1.

12. The method of treatment ozerinina point of view the number of connections on p. 9 or its salts.

13. A method of treating diabetes in a mammal, which consists in the introduction in need of such treatment, the patient is effective from the pharmaceutical point of view the number of connections on p. 1.

A method of treating diabetes in a mammal, which consists in the introduction in need of such treatment, the patient is effective from the pharmaceutical point of view the number of connections on p. 9 or its salts.

 

Same patents:

The invention relates to 4-oxocyclohexyl the urea compounds of General formula (I), where X, Y, R, R1, R2, R3, R4, R5And L, such as defined in the claims

The invention relates to 4-hydroxy-3-chinainternational and hydrazides of General formula (I), where a represents a-CH2- or-NH-, a R1, R2, R3and R4such as defined in the claims

The invention relates to new optically active proizvodnim of benzopyran formula

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where R and R are independently selected from the group consisting of hydroxyl and a moiety that can be converted in vivo in hydroxyl, such as acyloxy, -OR4, -OC(O)R7or-OC(O)OR4(where R4represents alkyl, alkenyl, quinil or aryl; and R7represents amino, alkylamino, aminoalkyl and alkylsulfonyl); and R3represents-CH2- or-CH2CH2-; or its pharmaceutically acceptable salt, where the specified compound or salt is optically active because they contain more than 50% (by weight relative to all stereoisomers) 2S stereoisomers

The invention relates to compounds of formula (I)

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in which Ar1denotes a heterocyclic group, which represents a pyrazole which may be substituted by one or more radicals R1, R2or R3; Ar2denotes phenyl, naphthyl or tetrahydronaphthyl, each of which optionally is substituted by one to three groups R2; L denotes a saturated or unsaturated, branched or unbranched carbon C1-C10chain; in which one or more methylene groups are optionally independently replaced by O, NH or S, and in which the linking group is optionally substituted by 0-2 of doxography; Q has a value selected from a range of: a) phenyl, naphthyl, pyridine, imidazole, Piran, etc. b) tetrahydropyran, morpholine, thiomorpholine, thiomorpholine and t

The invention relates to amide derivative of the formula I

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where R3represents (1-6C)alkyl or halogen; m is 0, 1, 2 or 3; R1represents hydroxy, halogen, trifluoromethyl, nitro, amino, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl] amino, amino-(2-6C)alkylamino, (1-6C)alkylamino-(2-6C)alkylamino etc

The invention relates to derivatives of cyclic amines and their use as pharmaceuticals, particularly to a compound represented by the General formula (I), its pharmaceutically acceptable acid additive salts or its pharmaceutically acceptable C1-C6alcaldicios salt, R1-phenyl, C3-8-cycloalkyl, aromatic heterocycle with 1-3 heteroatoms selected from O, S, N, or combinations thereof, and these groups may be condensed with benzene ring or an aromatic heterocyclic group with heteroatoms, selected from O, S or N, or combinations thereof, and may also have different substituents

The invention relates to new salts of pyridinium General formula (I) or their pharmaceutically acceptable salts, where R1is-R4- R5or-N(R7)N(R7R9, R4choose from the group of-N(R7R6O-, N(R7R6N(R7), -OR6O-,

-OR SIG6N(R7)-, where R6- alkyl, R5choose from the group of alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7Is H, alkyl or aryl, including heteroaryl, R2Is F, Cl, Br, J, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10or C(O)or SIG7, m = 0, 1, or 2, R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8, R8is R7OR7and NR7R10, R9is hydrogen, alkyl, aryl, including heteroaryl, -C(O)R10, -SO2R10, -C(S)OTHER10, -C(NH)NH(R10), -C(O)OTHER10, R10- H, alkyl, or aryl, including heteroaryl, and in each case, it is not necessarily different from R7X represents an ion halogen provided that 1) when two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (2) nitrogen heteroaryl ring R1

The invention relates to new N-phenylamine and N-pyridylamine derivative of the formula I

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in which X denotes O or S;

R1and R2which may be identical or different, denote hydrogen, (C1-C6)alkyl or (C3-C8)cycloalkyl or R1and R2together with the carbon atom to which they are attached, form a (C3-C8)cycloalkyl;

R3means (C6-C12)aryl, optionally substituted by one or more radicals Y, which may be the same or different;

Y represents halogen;

R4and R5represent hydrogen;

Ar denotes one of the following groups or WITH:

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T represents hydrogen or (C1-C6)alkyl;

T3and T4which may be identical or different, denote (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)allylthiourea;

R6and R7each denotes hydrogen or R6and R7together represent a bond;

Z denotes either (I) the divalent group-CHR9- in which the R11-, in which R10and R11together they form a bond that Z represents the group-CH=CH-, or R10and R11that may be the same or different, have the meanings indicated above for R9or (III) a divalent group-CHR12-CHR13-CH2-, in which R12and R13together they form a bond, Z represents-CH=CH-CH2-, or R12and R13that may be the same or different, have the meanings indicated above for R9,

as well as their additive salts with pharmaceutically acceptable acids or bases, and method of production thereof, pharmaceutical compositions and drug manifesting gipolipedimecescoe and antiatherosclerotic action based on them

The invention relates to new N-phenylamine and N-pyridylamine derivative of the formula I

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in which X denotes O or S;

R1and R2which may be identical or different, denote hydrogen, (C1-C6)alkyl or (C3-C8)cycloalkyl or R1and R2together with the carbon atom to which they are attached, form a (C3-C8)cycloalkyl;

R3means (C6-C12)aryl, optionally substituted by one or more radicals Y, which may be the same or different;

Y represents halogen;

R4and R5represent hydrogen;

Ar denotes one of the following groups or WITH:

< / BR>
T represents hydrogen or (C1-C6)alkyl;

T3and T4which may be identical or different, denote (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)allylthiourea;

R6and R7each denotes hydrogen or R6and R7together represent a bond;

Z denotes either (I) the divalent group-CHR9- in which the R11-, in which R10and R11together they form a bond that Z represents the group-CH=CH-, or R10and R11that may be the same or different, have the meanings indicated above for R9or (III) a divalent group-CHR12-CHR13-CH2-, in which R12and R13together they form a bond, Z represents-CH=CH-CH2-, or R12and R13that may be the same or different, have the meanings indicated above for R9,

as well as their additive salts with pharmaceutically acceptable acids or bases, and method of production thereof, pharmaceutical compositions and drug manifesting gipolipedimecescoe and antiatherosclerotic action based on them

New salt // 2193560
The invention relates to a new salt - acid tartrate (R)-3-N,N-dicycloverine-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide, in particular its (2R, 3R)-tartrate and especially acid monohydrate (2R,3R)-tartrate of (R)-3-N,N-dicycloverine-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide, as well as to a method for the specified tartrate salts and pharmaceutical compositions based on it for the treatment and prevention of disorders of the Central nervous system and related medical abuses associated with the activity of the antagonist 5-HT1A-receptor

The invention relates to new compounds 2,4-xylidide and m-phenetidine 2-acetylaminofluorene-3-carboxylic acid of General formula 1

,

where Ia) R=2,4-(CH3)2WITH6H3; IB) R=m-C2H5OS6H4that possess anticoagulant activity and can be used in medicine

The invention relates to a new method for the preparation of 3-N,N-dicycloverine-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide in the form of racemic compounds or R - or S-enantiomers of the formula

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and their pharmaceutically acceptable salts, as well as intermediate products received and used in the specified way of formulae V-X:

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The technical result is to simplify the process by eliminating the stage of fluorination, and also due to the fact that this method allows to exclude the receipt of byproduct

The invention relates to a new crystalline (-)-3R,4R-TRANS-7-methoxy-2,2-dimethyl-3-phenyl-4-{ 4-[2-(pyrrolidin-1-yl)ethoxy] phenyl} chromane hydrofolate, method thereof, pharmaceutical compositions on the basis and method of reducing or preventing the rarefaction of bone, including the introduction to the patient an effective amount of the specified new connection

The invention relates to new Bermatingen compounds, the United propylenebis communication, General formula I where Ar represents a radical of formula (a) or (b), R1is-OR6or-COR7, R2represents a polyether radical, comprising 1 to 6 carbon atoms and 1 to 3 atoms of oxygen or sulfur, and if in the latter case, R4represents a linear or branched C1-C20alkyl, he is in ortho - or meta-position relative to X-Ar connection, R3represents lower alkyl, or R2or R3taken together form a 6-membered ring, optionally substituted by at least one of the stands and/or optional split the atom of oxygen or sulfur, R4represents H, linear or branched C1-C20alkyl or aryl, R5represents H or-OR8, R6represents H, R7represents H, -OR10or-N(r)r (r) r are H, lower alkyl or taken together with the nitrogen atom form a ring of morpholino, R8represents H or lower alkyl, R10represents H, linear or branched C1-C20alkyl, X represents a divalent radical, which is from right to left or Vice versa has the formula (d), R11Fri carboxylic acid and the optical and geometrical isomers of the above compounds of formula (I)

The invention relates to substituted chromalusion (thio)ureas of the formula (I):

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where R (1) denotes hydrogen, alkyl with 1-4 C-atoms, alkoxy with 1-4 C-atoms, fluorine, chlorine, bromine, iodine, CF3, NH2, NH-alkyl with 1-4 C-atoms, N(alkyl)2with 1-4 C-atoms in the same or different alkyl residues, or S-alkyl with 1-4 C-atoms;

R (2a) denotes hydrogen or alkyl with 1 or 2 C-atoms;

R (2b) and R (2d), which are identical or different, denote hydrogen, alkyl with 1 or 2 C-atoms not substituted phenyl, substituted phenyl, unsubstituted benzyl or substituted phenyl residue, benzyl, and as the substituents in the phenyl residues are up to three identical or different substituents selected from the group consisting of hydrogen, halogen, alkyl with 1 or 2 C-atoms, alkoxyl with 1 or 2 C-atoms;

R (2c) and R (2e), which are identical or different, denote hydrogen or alkyl with 1 or 2 C-atoms;

R (3) denotes hydrogen, alkyl with 1,2,3 or 4 C-atoms, cycloalkyl with 3, 4, 5 or 6 C-atoms in the ring, CH2-cycloalkyl with 3, 4, 5 or 6 C-atoms in the ring, or CF3;

Q represents (CH2)n;

where n = 1 or 2;

Z denotes serousily, selected from the group consisting of hydrogen, halogen, alkyl with 1 or 2 C-atoms, alkoxyl with 1 or 2 C-atoms;

or

A denotes the residue of a saturated or unsaturated lactam of the formula:

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where B denotes albaniles or alkylene with 3, 4, 5 or 6 C-atoms, which is unsubstituted or substituted by up to three identical or different alkyl groups with 1, 2, 3 or 4 C-atoms;

or

A denotes the residue of a bicyclic system of the formula:

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and their physiologically acceptable salts

The invention relates to bicyclic compounds useful as drugs, the neutralizing effect of glycoprotein IIb/IIIa, to prevent thrombosis

The invention relates to non-steroidal anti-inflammatory drugs, particularly to substituted dihydrobenzofuran and related compounds

The invention relates to new derivatives of amino(thio)ethers of the formula I

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where X represents oxygen, sulfur, sulfinil, sulfonyl or, if R0and R1together are not alkalinous chain with 1 to 3 atoms, CH2:

Z represents -(CH2)n1-(CHA)n2-(CH2)n3and

n1 = 0, 1, 2 or 3,

n2 = 0 or 1,

n3 = 0, 1, 3 or 3, provided that

n1 + n2 + n3 < 4;

R0represents hydrogen or A;

R1represents hydrogen, A, OA, phenoxy, Ph, OH, F, Cl, Br, CN, CF3, COOH, COOA, acyloxy with 1-4 carbon atoms, carboxamido, -CHNH2, -CH2NHA, -CH2NA2,

-CH2NHAc, -CH2NHSO2CH3,

or

R0and R1together represent alkylenes chain with 1 to 3 carbon atoms or alkenylamine chain with 2 to 3 carbon atoms;

R2represents hydrogen, A, Ac, or-CH2-R4;

R3represents-CH2-R4or-CHA-R4;

R4is a Ph, 2-, 3 - or 4-pyridyl (unsubstituted or monosubstituted R5) or thiophene (unsubstituted, mono - or disubstituted by A, OA, OH, F, Cl, Br, CN and/or CF3or the other what it is, di-, tri-, Tetra-, or pentamidine F, CF3partially or fully fluorinated A, A and/or OA;

R6, R7, R8and R9each independently represents H, A, OA, phenoxy, OH, F, Cl, Br, I, CN, CF3, NO2, NH2, NHA, NA2, Ac, Ph, cycloalkyl c 3-7 carbon atoms, -CH2NH2, -CH2NHA, -CH2NA2, -CH2N HAC or-CH2NHSO2CH3or two coming together constitute the remainder alkylenes chain with 3-4 carbon atoms, and/or R1and R6together predstavljaet a chain with 3 or 4 carbon atoms;

A represents alkyl with 1-6 carbon atoms;

Ac is alkanoyl with 1-10 carbon atoms or aroyl with 7 to 11 carbon atoms;

Ph represents phenyl (unsubstituted or substituted R5, 2-, 3 - or 4-pyridium or phenoxyl group);

and physiologically acceptable salts, their derivatives

The invention relates to N-acylated to pseudodipeptides corresponding to General formula I

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in which R1and R2denote each acyl group of the carboxylic acid having from 2 to 24 carbon atoms, which may be saturated or unsaturated, linear or branched, unsubstituted or having one or more substituents selected from hydroxyl, alkyl, alkoxy groups, acyloxy, amino, acylamino, atillio and C1-C24alkylthio; handles m, p and q can take values from 1 to 10; descriptor n can take values from 0 to 10; X and Y each represent hydrogen or an acid group selected from the following groups: carboxy-C1-C5-alkyl, -CH-[(CH2)mCOOH][(CH2)nCOOH], where m = 0-5 and n = 0-5, phosphono-C1-C5-alkyl, dihydroxystearic-C1-C5-alkyl, dimethoxyphosphoryl, phosphono, hydroxysulfonic, hydroxysulfonic-C1-C5-alkyl, hydroxysulfonic C1-C5-alkyl in neutral or charged form, provided that at least one of the substituents X and Y designates defined above acid group in neutral or charged Faure is memlimit salts, the method of production thereof and pharmaceutical composition having immunomodulatory properties, containing as active ingredient at least one compound of General formula I
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