Indeno-, naphtho-, and benzocycloheptadihydrothiazole derivatives, production thereof and uses as anorexia pharmaceuticals

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to polycyclic dihydrothiazoles of formula I , containing in substituted alkyl residues in 2-posiiton, as well as physiologically accepted salts thereos, having anorexia action. In formula Y is direct bond; X is CH2; R1 and R1' are independently H, Cl; R2 and R3 are H; R4 is (C8-C16-cycloalkyl, (CH2)n-A-R8, wherein n = 1-6, excepted group of formula -CH2-O-CH2-phenyl with unsubstituted phenyl; A is O, S; R8 is methyl or (CH2)m-aryl, where in m = 0-6; and aryl may represent phenyl, wherein aryl group may be optionally substituted with one or two substituents, selected from Cl, O-(C1-C6)-alkyl or (C1-C6)-alkyl. Also disclosed is method for production thereof.

EFFECT: new anorexia pharmaceuticals.

5 cl, 4 ex, 2 tbl

 

Polycyclic containing in position 2 substituted alkyl residues of dihydrothiazolo, method of their production and their use as pharmaceuticals.

The invention relates to polycyclic to dihydrothiazolo, and their physiologically acceptable salts and physiologically active derivatives.

Derivatives of thiazolidine with anorexically (i.e. overwhelming appetite) action already described in the prior art (patent Austria No. 365181).

The basis of the invention is to obtain new compounds exhibiting therapeutically suitable anorexically action.

Thus, the invention relates to compounds of formula (I):

where Y represents a direct bond, -CH2-, -CH2-CH2-;

X is CH2CH(CH3), CH(C2H5), SN(C3H7), CH(C6H5);

R1, R1’, independently of one another, denote H, F, Cl, Br, I, CF3NO2, CN, COOH, COO-(C1-C6)-alkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-quinil, O-(C1-C6)-alkyl, and alkyl residues one, several or all of the hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3THAT IS C(O)N, O-CH2-C6H5, NH2, NH-CO-CH3or N(COOCH2C6H5)2; SO2-NH2, SO2NH-(C1-C6)-alkyl, SO2N-[(C1-C6)-alkyl]2S-(C1-C6)-alkyl, S-(CH2)n-phenyl, SO-(C1-C6)-alkyl, SO-(CH2)n-phenyl, SO2-(C1-C6)-alkyl, SO2-(CH2)n-phenyl, and n can mean 0-6 and the phenyl residue may be substituted by substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, NH2; NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-(C1-C7)-acyl, phenyl, biphenyl. O-(CH2)n-phenyl, and n can mean 0-6, 1 - or 2-naphthyl, 2-, 3 - or 4-pyridyl, 2 - or 3-furanyl or 2 - or 3-thienyl, and phenyl, biphenylene, raftiline, peredelnye, foronline or thienyl rings may be substituted by substituents in an amount up to three, inclusive, selected from F, Cl, Br, I, HE, CF3, NO2CN, F3About-(C1-C6)-alkyl, (C1-C6)-alkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, SO2-CH3, COOH, COO-(C1-C6)-alkyl, CONH2; 1,2,3-triazole-5-yl, and triazole number of the person in position 1, 2 or 3 may be replaced by stands or benzyl;

tetrazol-5-yl, and tetrazole the ring in position 1 or 2 can be replaced by stands or benzyl;

R2 denotes H, (C1-C6)-alkyl, (C3-C6-cycloalkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, C(O)-(C1-C6)-alkyl, C(O)-(C3-C6-cycloalkyl, C(O)-(CH2)n-phenyl, C(O)-(CH2)n-thienyl, C(O)-(CH2)n-pyridyl, C(O)-(CH2)n-furyl, and n can mean 0-5 and where the phenyl, thienyl, pyridyl, furyl, respectively, may be replaced by alternates in the amount of up to two, inclusive, selected from Cl, F, CN, CF3, (C1-C3)-alkyl, HE, O-(C1-C6)-alkyl;

R3 denotes H, (C1-C6)-alkyl, F, CN, N3, O-(C1-C6)-alkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, and n can mean 0-5 and where the phenyl, thienyl, pyridyl, furyl, respectively, may be replaced by alternates in the amount of up to two, inclusive, selected from Cl, F, CN, CF3, (C1-C3)-alkyl, HE, O-(C1-C6)-alkyl, (C2-C6)-quinil, (C1-C6)-alkenyl, C(O)och3With(O)och2CH3With(O)HE, C(O)NH2With(O)N3With(O)N(With the 3)2, OS(O)CH3;

R4 means (C8-C16-cycloalkyl, and in the alkyl residues of one or more hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH3-phenyl or-(C1-C4)-alkyl;

(CH2)n-A-R8, and n may indicate 1-6; and excluded group-CH2-O-CH2-phenyl, where phenyl unsubstituted;

(CH2)rIn R9, and r may indicate 1-6;

A represents O, S, SO, SO2;

In the mean NH, N-(C1-C6)-alkyl, NCHO, N(CH3);

R8 means (C5-C24)-alkyl, (C3-C10-cycloalkyl, and in the alkyl residues of one or more hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-phenyl or O-(C1-C4)-alkyl; (CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, naphthyl, biphenyl, thienyl or pyridyl and aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-C8)-alkyl, SO2-N-[(C1-C8)-alkyl]2, SO -NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl]-SO2-(C1-C8)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in the number to two, inclusive, selected from F, Cl, CN, IT, (C1-C6)-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)pis phenyl or SO2-(CH2)p-phenyl, and R may mean 0-3;

R9 denotes (CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, n is ftil, biphenyl, thienyl or pyridyl;

and the aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-C8)-alkyl, SO2-N-[(C1-C8)-alkyl]2, SO2-NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl]-SO2-(C1-C8)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in the number to two, inclusive, selected from F, Cl, CN, (C1-C )-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)R-phenyl, or SO2-(CH2)p-phenyl, and R may mean 0-3;

and their physiologically acceptable salts.

Preferred compounds of formula (I), where

Y represents a direct bond;

X is CH2;

R1, R1’, independently of one another, denote H, F, Cl, Br, I, CF3, NO2, CN, COOH, COO-(C1-C6)-alkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-quinil, O-(C1-C6)-alkyl, and alkyl residues one, several or all of the hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-C6H5, NH2, NH-CO-CH3or N(COOCH2C6H5)2; SO2-NH2, SO2NH-(C1-C6)-alkyl, SO2N-[(C1-C6)-alkyl]2S-(C1-C6)-alkyl, S-(CH2)n-phenyl, SO-(C1-C6)-alkyl, SO-(CH2)n-phenyl, SO2-(C1-C6)-alkyl, SO2-(CH2)n-Fe is Il, moreover, n may mean 0-6 and the phenyl residue may be substituted by substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, NH2; NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-(C1-C7)-acyl, phenyl, biphenyl. O-(CH2)n-phenyl, and n can mean 0-6, 1 - or 2-naphthyl, 2-, 3 - or 4-pyridyl, 2 - or 3-furanyl or 2 - or 3-thienyl, and phenyl, biphenylene, raftiline, peredelnye, foronline or thienyl rings may be substituted by substituents in an amount up to three, inclusive, selected from F, Cl, Br, I, HE, CF3, NO2CN, F3About-(C1-C6)-alkyl, (C1-C6)-alkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, SO2-CH3, COOH, COO-(C1-C6)-alkyl, CONH2;

1,2,3-triazole-5-yl, and triazole ring in position 1, 2 or 3 may be replaced by stands or benzyl;

tetrazol-5-yl, and tetrazole the ring in position 1 or 2 can be replaced by stands or benzyl;

R2 denotes H, (C1-C6)-alkyl, (C3-C6-cycloalkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, C(O)-(C1- 6)-alkyl, C(O)-(C3-C6-cycloalkyl, C(O)-(CH2)n-phenyl, C(O)-(CH2)n-thienyl, C(O)-(CH2)n-pyridyl, C(O)-(CH2)n-furyl, and n can mean 0-5 and where the phenyl, thienyl, pyridyl, furyl, respectively, may be replaced by alternates in the amount of up to two, inclusive, selected from Cl, F, CN, CF3, (C1-C3)-alkyl, HE, O-(C1-C6)-alkyl;

R3 denotes H, (C1-C6)-alkyl, F, CN, N3, O-(C1-C6)-alkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, and n can mean 0-5 and where the phenyl, thienyl, pyridyl, furyl, respectively, may be replaced by alternates in the amount of up to two, inclusive, selected from Cl, F, CN, CF3, (C1-C3)-alkyl, HE, O-(C1-C6)-alkyl, (C2-C6)-quinil, (C2-C6)-alkenyl, C(O)och3With(O)och2CH3With(O)HE, C(O)NH2C(O)NHCH3With(O)N(CH3)2, OS(O)CH3;

R4 means (C8-C16-cycloalkyl, and in the alkyl residues of one or more hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-phenyl or O-(C1-C4)-alkyl;

(CH2)n-A-R8, and n may indicate 1-6;

priceincludes group-CH 2-O-CH2-phenyl, where phenyl unsubstituted;

(CH2)r-B-R9, and r may indicate 1-6;

A represents O, S, SO, SO2;

In the mean NH, N-(C1-C6)-alkyl, NCHO, N(CH3);

R8means (C5-C24)-alkyl, (C3-C10-cycloalkyl, and in the alkyl residues of one or more hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-phenyl or-(C1-C4)-alkyl;

(CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, naphthyl, biphenyl, thienyl or pyridyl;

and the aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-C8)-alkyl, SO2-N-[(C1-C8)-alkyl]2, SO2-NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-Cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-is cloacina, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl]-SO2-(C1-C8)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in the number to two, inclusive, selected from F, Cl, CN, (C1-C6)-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)pis phenyl or SO2-(CH2)p-phenyl, and R may mean 0-3;

R9 denotes (CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, naphthyl, biphenyl, thienyl or pyridyl; and the aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-sub> 8)-alkyl, SO2-N-[(C1-C8)-alkyl]2, SO2-NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl]-SO2-(C1-C8)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in the number to two, inclusive, selected from F, Cl, CN, IT, (C1-C6)-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)pis phenyl or SO2-(CH2)p-phenyl, and R may mean is 0-3;

and their physiologically acceptable salts.

Especially preferred compounds of formula (I), where

Y represents a direct bond;

X is CH2;

R1, R1’, independently of one another, denote H, F, Cl, Br, I, CF3, NO2, CN, COOH, COO-(C1-C6)-alkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-quinil, O-(C1-C6)-alkyl, and alkyl residues one, several or all of the hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-C6H5, NH2, NH-CO-CH3or N(SOON2With6H5)2; SO2-NH2, SO2NH-(C1-C6)-alkyl, SO2N-[(C1-C6)-alkyl]2S-(C1-C6)-alkyl, S-(CH2)n-phenyl, SO-(C1-C6)-alkyl, SO-(CH2)n-phenyl, SO2-(C1-C6)-alkyl, SO2-(CH2)n-phenyl, and n can mean 0-6 and the phenyl residue may be substituted by substituents in the number to two, inclusive, selected from F, CL, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, NH2;

NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2N-(C 1-C7)-acyl, phenyl, biphenyl, O-(CH2)n-phenyl, and n can mean 0-6, 1 - or 2-naphthyl, 2-, 3 - or 4-pyridyl, 2 - or 3-furanyl or 2 - or 3-thienyl, and phenyl, biphenylene, raftiline, peredelnye, foronline or thienyl rings may be substituted by substituents in an amount up to three, inclusive, selected from F, Cl, Br, I, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, SO2-CH3, COOH, COO-(C1-C6)-alkyl, CONH2;

1,2,3-triazole-5-yl, and triazole ring in position 1, 2 or 3 may be replaced by stands or benzyl;

tetrazol-5-yl, and tetrazole the ring in position 1 or 2 can be replaced by stands or benzyl;

R2 denotes H, (C1-C6)-alkyl, (C3-C6-cycloalkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, C(O)-(C1-C6)-alkyl, C(O)-(C3-C6-cycloalkyl, C(O)-(CH2)n-phenyl, C(O)-(CH2)n-thienyl, C(O)-(CH2)n-pyridyl, C(O)-(CH2)n-furyl, and n can mean 0-5 and where the phenyl, thienyl, pyridyl, furyl, respectively, may be replaced by alternates in the amount of up to two, inclusive, in the swear of Cl, F, CN, CF3, (C1-C3)-alkyl, HE, O-(C1-C6)-alkyl;

R3 denotes H, F;

R4 means (C8-C16-cycloalkyl, and in the alkyl residues of one or more hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-phenyl or-(C1-C4)-alkyl;

(CH2)n-A-R8, and n may indicate 1-6;

moreover, the excluded group-CH2-O-CH2-phenyl, where phenyl unsubstituted;

(CH2)r-B-R9, and r may indicate 1-6;

A represents O, S;

In the mean NH, N-(C1-C6)-alkyl, NCHO, N(CH3);

R8 means (C5-C24)-alkyl, (C3-C10-cycloalkyl, and in the alkyl residues of one or more hydrogen atoms may be replaced by fluorine, or one hydrogen atom may be replaced by HE, OC(O)CH3, OS(O)H, O-CH2-phenyl or-(C1-C4)-alkyl;

(CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, naphthyl, biphenyl, thienyl or pyridyl; and the aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-C8-alkyl, SO2-N-[(C1-C8)-alkyl]2, SO2-NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NN-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl]-SO2-(C1-C6)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in the number to two, inclusive, selected from F, Cl, CN, (C1-C6)-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)pis phenyl or SO2-(CH2)p-phenyl, and R may mean 0-3;

R9 denotes (the N 2)m-aryl, and m=0-6, and the aryl may mean phenyl, naphthyl, biphenyl, thienyl or pyridyl; and the aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-C8)-alkyl, SO2-N-[(C1-C8)-alkyl]2, SO2-NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl] -SO2-(C1-C6)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in kolichestvo two, inclusive, selected from F, Cl, CN, (C1-C6)-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)pis phenyl or SO2-(CH2)p-phenyl, and R may mean 0-3;

and their physiologically acceptable salts.

Highly preferred compounds of formula (I), where

Y represents a direct bond;

X is CH2;

R1, R1’, independently of one another, denote H, F, Cl, Br, I, (C1-C6)-alkyl;

R2 denotes H, (C1-C6)-alkyl;

R3 denotes H, F;

R4 means (C8-C16-cycloalkyl or (CH2)n-A-R8, and n may indicate 1-6 and, moreover, excluded group-CH2-O-CH2-phenyl, where phenyl unsubstituted;

A represents O, S;

R8 means (C5-C24)-alkyl or (CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, and aryl part can be substituted by the substituents in the number to two, inclusive, selected from F, Cl, Br, HE, CF3, NO2CN, F3, O-(C1-C6)-alkyl, S-(C1-C6)-alkyl, SO-(C1-C6)-alkyl, SO2-(C1-C6)-alkyl, SO2-NH2, SO2-NH-(C1-C8)-alkyl, SO 2-N-[(C1-C8)-alkyl]2, SO2-NH-(C3-C8)-cycloalkyl, SO2-N-[(C3-C8-cycloalkyl]2, (CH2)m-SO2-NH2, (CH2)m-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2where m may indicate 1-6, SO2-N=CH-N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO-(C1-C6)-alkyl, COO-(C3-C6)-cycloalkyl, CONH2, CONH-(C1-C6)-alkyl, CON-[(C1-C6)-alkyl]2, CONH-(C3-C6)-cycloalkyl, NH2, NH-(C1-C6)-alkyl, N-[(C1-C6)-alkyl]2, NH-CO-(C1-C6)-alkyl, NH-CO-phenyl, NH-SO2-(C1-C8)-alkyl, N-[(C1-C6)-alkyl]-SO2-(C1-C8)-alkyl, NH-SO2-phenyl, and the phenyl ring may be substituted by substituents in the number to two, inclusive, selected from F, Cl, CN, (C1-C6)-alkyl, O-(C1-C6)-alkyl, CF3, COOH, COO-(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholine-1-yl, piperidine-1-yl, piperazine-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O-(CH2)p-phenyl, S-(CH2)pis phenyl or SO2-(CH2)p-phenyl,

moreover, R can mean 0-3; and their physiological the automatic acceptable salt.

The invention relates to compounds of formula (I) in the form of their racemates, racemic mixtures and pure enantiomers, and to their diastereomers and their mixtures.

Alkyl, alkeline and alkyline residues in the substituents R1, R1’, R2, R3, R4, R8 and can be both linear and branched.

Pharmaceutically acceptable salts on the basis of their higher water solubility compared to the original, or base compounds are particularly suitable for applications in medicine. These salts must contain a pharmaceutically acceptable anion or cation. Suitable pharmaceutically acceptable additive salts of the compounds according to the invention with acids are salts of inorganic acids as hydrochloric acid, Hydrobromic acid, phosphoric acid, metaphosphoric acid, nitric acid, acid and sulfuric acid, and organic acids, such as acetic acid, benzosulfimide, benzoic acid, citric acid, econsultation, fumaric acid, gluconic acid, glycolic acid, setinova acid, lactic acid, lactobionic acid, maleic acid, malic acid, methanesulfonate, succinic acid, p-toluensulfonate, tartaric acid and triperoxonane acid. For medical purposes especially preferably using salt salt sour the s. Suitable pharmaceutically acceptable basic salts are ammonium salts, alkali metal salts (like sodium and potassium salts), and salts of alkaline earth metals (as magnesium salt and calcium).

Salts with a pharmaceutically unacceptable anion are also included in the scope of the invention as useful intermediates for obtaining or purification of pharmaceutically acceptable salts and/or for use in non-therapeutic purposes, for example, applications in in vitro.

Used in the present description, the term "physiologically functional derivative" refers to any physiologically acceptable derivative proposed according to the invention the compounds of formula (I), for example, ester, which when administered to a mammal, such as man, is able (directly or indirectly) to form a compound of formula (I) or its active metabolite.

To physiologically functional derivatives also include proletarienne forms of the compounds according to the invention. Such prodrugs can be metabolised in vivo to the compounds according to the invention. These prodrugs may themselves be active or not.

Proposed according to the invention compounds may be present in various polymorphic forms, for example as amorphous and crystalline polymorphous forms. All polymorphic formicoxenini according to the invention are within the scope of the invention and constitute a further aspect of the invention.

In the following text, all references to "compound (compounds) according to the formula (I)" refers to the compound (compounds) of the formula (I)as described above, and their salts, solvate and physiologically active derivative, as described in the present description.

The number of compounds according to formula (I), which is necessary to achieve the desired biological effect depends on a number of factors, for example, selected from specific connections, intended use, method of administration and the clinical condition of the patient. In General, the daily dose amount in the range from 0.3 mg to 100 mg (typically from 3 mg to 50 mg) per day per kilogram of body weight, for example, 3-10 mg/kg per day. An intravenous dose may be, for example, from 0.3 mg to 1.0 mg/kg, which can appropriately be introduced in the form of infusion in the amount of 10-100 ng per kilogram per minute. Suitable infusion solutions for these purposes may include, for example, from 0.1 ng to 10 mg, typically from 1 ng to 10 mg, the biologically active substance per milliliter. Single doses may contain, for example, from 1 mg to 10 g of biologically active substances. Thus, ampoules for injection may contain, for example, 1-100 mg, oral insertion of the dosage form in the form of single doses, as, for example, tablets or capsules, may contain, for example, from 1.0 to 1000 mg, typically 10-600 mg of biologically active substances. In the case of pharmaceutically acceptable salts of the above weight data relate to the weight is manufactured from salt ion dihydrothiazolo. For the prevention or therapy of the abovementioned conditions, the compounds according to formula (I) can be used individually in the form of compounds, however, preferably together with an acceptable carrier in the form of pharmaceutical compositions. The media, of course, must be acceptable in the sense that it is compatible with other components of the composition and is not harmful to the health of the patient. The carrier may be solid or liquid or both, and preferably it is used together with the compound for the preparation of dosage forms in the form of a single dose, for example, in the form of a tablet, which may contain from 0.05 to 95 wt.% biologically active substances. May be other pharmaceutically active agents, including other compounds according to formula (I). Proposed according to the invention the pharmaceutical composition can be obtained according to one of the known pharmaceutical methods, which essentially consist in the fact that the components are mixed with pharmacologically acceptable carriers and/or auxiliary substances.

Proposed according to the invention pharmaceutical compositions are such, which is suitable for oral, rectal, local, peroral (for example sublingual) and parenteral (e.g. subcutaneous, intramuscular, intradermal or intravenous) administration, although the most suitable route of administration in each case depends on the type and severity of the treated condition and the kind used in each case, the compounds according to formula (I). In the scope of the invention also includes index products and index prolonged dosage forms. Preferred are resistant to the action of acid and gastric juice dosage forms. Suitable, resistant to gastric juice coating include acetated cellulose, polyvinylacetate, phthalate of hydroxypropylmethylcellulose and anionic polymers of methacrylic acid and methyl methacrylate.

Suitable pharmaceutical compounds for oral administration may be in the form of separate units, such as capsules, capsule shell, tablets for sucking or tablets, which contain, respectively, a certain number of compounds according to formula (I); as powders or granules; as solution or suspension in an aqueous or nonaqueous liquid; or as an emulsion oil-in-water or water-in-oil. These compositions, as mentioned, can be obtained by any suitable pharmaceutical methods, which include stud is Yu, which enter into contact with the biologically active substance and the carrier (which may consist of one or more additional components). In General, the composition is prepared by uniform and homogeneous mixing of the biologically active substance with a liquid and/or finely dispersed solid carrier, after which the product, if necessary, is formed. For example, you can get a tablet so that the powder or granular compounds of pressed or molded, if necessary, together with one or more additional components. Compressed tablets can be obtained by tabletting in a suitable machine, the compound in free-flowing form such as powder or granules, if necessary, mixed with a binder, which imparts lubricity tablets substance, inert diluent and/or one (several) surface-active our/the dispersant. Molded tablets can be obtained by molding in a suitable machine powder, moistened with an inert liquid diluent connection.

Pharmaceutical compositions suitable for peroral (sublingual) administration include tablets for sucking, which contain the compound according to formula (I) with a flavoring substance, usually sucrose and gum Arabic or Trianta, and pastels is, which contain the compound in an inert basis as gelatin and glycerol or sucrose and gum Arabic.

Suitable pharmaceutical compositions for parenteral administration preferably include sterile aqueous compositions of the compounds according to formula (I), which are preferably isotonic with the blood provided the recipient. These compositions are preferably injected intravenously, although it can also be performed by a subcutaneous, intramuscular or intradermal injection in the form of injections. These compositions preferably can be prepared by a method in which the compound is mixed with water and the resulting solution make sterile and isotonic with blood. Proposed according to the invention compositions for injection include, in General, 0.1 to 5 wt.% active connection.

Pharmaceutical compositions suitable for rectal administration, preferably have the form of disposable suppositories dosage. They can be prepared by a method in which a compound according to formula (I) is mixed with one or more conventional solid carriers, such as cocoa butter, and the resulting mixture introduced into the form.

Pharmaceutical compositions suitable for local application on the skin, preferably have the form of ointment, cream, lotion, paste, spray, aerosol or oil. As carriers can use the ü vaseline, lanolin, polyethylene glycols, alcohols and combinations of two or more of these substances. The biologically active substance is, in General, in a concentration of 0.1-15 wt.%, in relation to the weight of the composition, for example, 0.5 to 2 wt.%.

It is also possible percutaneous introduction. Suitable pharmaceutical compositions for percutaneous applications can be in the form of individual patches that are suitable for long-term close contact with the epidermis of the patient. Such patches in a convenient case contains biologically active substance, if necessary, in buffered aqueous solution, dissolved and/or dispersed in an adhesive or dispersed in the polymer. A suitable concentration of biologically active substances is about 1-35%, preferably about 3-15%. As a special ability, such as described in Pharmaceutical Research, 2 (6), 318 (1986), the biologically active substance may be released by elektrotransportirovka or electrophoresis.

The object of the invention, then, is a method of obtaining compounds of General formula (I), characterized in that compounds of the formula (I) receive as a result of that act according to the following reaction scheme:

for this purpose, compounds of General formula (II):

where R1, R1’, R3 is X and Y have the indicated meaning, activate and transferred to the compound of formula (III), where Z denotes the residue of an activated ester of an inorganic or organic acid.

The compounds of formula (III) is then injected into the interaction with thioamides of the formula (VI):

where R4 has the specified value to obtain the compounds of formula (VII), respectively, of formula (I’), and, if necessary, the compounds of General formula (I’) with organic or inorganic acids transferred to their acid additive salts of the formula (VII) or the salts of formula (VII) with organic or inorganic bases transferred to free basic forms of the compounds of formula (I’).

As inorganic acids are used, for example, halogen acids as hydrochloric acid and Hydrobromic acid, and also sulfuric acid, phosphoric acid and amidosulfonic.

As organic acids should be called, for example, formic acid, acetic acid, benzoic acid, p-toluensulfonate, benzosulfimide, succinic acid, fumaric acid, maleic acid, lactic acid, tartaric acid, citric acid, L-ascorbic acid, salicylic acid, isetionate acid, methanesulfonate, triftormetilfullerenov, 1,2-benzisothiazol-3(2H)-he, 6-methyl-1,2,3-oxathiazin-4(3H)-one-2-dioxide.

The above method is preferably carried out so that the compounds of the formula (III) enter into interaction with thioamides of the formula (VI) in a molar ratio of from 1:1 to 1:1,5. The reaction is preferably carried out in an inert solvent, for example, in polar organic solvents, such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, dioxane, tetrahydrofuran, acetonitrile, nitromethane or diethylethylenediamine ether. As a particularly preferred solvents, however, may be mentioned methyl acetate and ethyl acetate, alcohols, short-chain as methanol, ethanol, propanol, isopropanol, and the lowest dealkylation, as, for example, acetone, butane-2-one or hexane-2-it. It is also possible to use mixtures of these reaction media; and it is also possible to use mixtures of these solvents with solvents that are less suitable for independent use, as, for example, mixtures of methanol with benzene, ethanol with toluene, methanol, diethyl ether or tert-butyl methyl ether, ethanol with carbon tetrachloride, acetone, chloroform, dichloromethane or 1,2-dichloroethane, and the corresponding polar solvent is more appropriate to use in excess. Components of the reaction can be suspended or dissolved in an appropriate reaction medium. In principle, the component is s reaction you can enter into interaction also without solvent, especially when the appropriate thioamide has the lowest melting point. The reaction proceeds only weakly exothermically, and it can be performed at a temperature of 10-150°C, preferably 30-100°C. is Particularly favorable, as a rule, the temperature interval from 50°to 90°C.

The duration of reaction largely depends on the reaction temperature and ranges from 2 minutes to 3 days at higher, respectively, lower temperatures. In favorable temperature interval, the duration of the reaction is, in General, from 5 minutes to 48 hours.

Since the compounds of formula (VII) in the reaction is often deposited in a sparingly soluble form of their acid additive salts is additionally convenient to add a suitable precipitant. As such, using, for example, hydrocarbons like benzene, toluene, cyclohexane or heptane, or carbon tetrachloride; in particular, especially suitable are alkalemia the acetic acid esters as ethyl acetate or n-butyl acetate, or a simple dialkyl ethers like diethyl ether, diisopropyl ether, di-n-butyl ether or tert-butyl methyl ether. If at the end of the reaction, the reaction mixture remains in solution, the salts of the compounds of the formula (VII), if necessary, can precipitate poslegarantiynogoi reaction solution by using one of these precipitators. In addition, the solution of the reaction mixture can also easily enter dropwise into a solution of one of these precipitators with stirring. Since the reaction of compounds of formula (III) with thioamides of the formula (VI) proceeds almost quantitatively obtained crude products often are analytically pure. Processing of the reaction mixture can also be implemented in such a way that the reaction mixture is alkalinized by adding an organic base, such as, for example, triethylamine, or diisobutylamine, or ammonia or morpholine, or piperidine, or 1,8-diazabicyclo[5,4,0]undec-7-ene, and the crude reaction product after concentration of purified chromatographically, for example, on a column of silica gel. Suitable eluting environments for this purpose are, for example, mixtures of ethyl acetate with methanol, mixtures of dichloromethane with methanol, mixtures of toluene with methanol or ethyl acetate or a mixture of ethyl acetate, hydrocarbons, such as heptane. If purification of the crude product is carried out is described by the last method, the thus obtained pure reason of the formula (I’) can be obtained the product of the joining of the acids of formula (VII) in such a way that the base is dissolved or suspended in proton organic solvent, such as methanol, ethanol, propanol or isopropanol, or in an aprotic organic is the solvent, such as ethyl acetate, diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, tetrahydrofuran, acetone, or butane-2-it, and this mixture is then mixed with at least equimolar amounts of an inorganic acid, such as hydrochloric acid, dissolved in an inert solvent, such as diethyl ether or ethanol, or another of the further above-mentioned inorganic or organic acids.

The compounds of formula (I’) can precrystallization of suitable inert solvent, such as, for example, acetone, butane-2-it, acetonitrile, nitromethane. Particularly preferably, however, pereosazhdeniya of solvent, such as, for example, dimethylformamide, dimethylacetamide, nitromethane, acetonitrile, preferably methanol or ethanol.

The reaction of compounds of formula (II) with thioamides of the formula (VI) can also be carried out in such a way that the reaction mixture are added in at least equimolar amount of base, such as triethylamine, and thus obtained the compounds of formula (I’), then, if necessary, transferred to their addition products of acids of the formula (VII).

In the compounds of the formula (III) as the remainder of the activated complex ester Z is used, for example, CL, Br, I, O-C(O)-(C6H4)-4-NO2,- SO2-CH3O-SO2-CF3O-SO 2-(C6H4)-4-CH3O-SO2-C6H4.

The addition products of acids of the formula (VII) and (I) x HZ by treatment with bases can be converted into compounds of General formula (I) and (I’). As the bases used, for example, solutions of inorganic hydroxides, as the hydroxide of lithium, sodium, potassium, calcium or barium; carbonates or bicarbonates like sodium carbonate or potassium bicarbonate, sodium or potassium, ammonia and amines as triethylamine, Diisopropylamine, dicyclohexylamine, piperidine, morpholine, methyldicyclohexylamine.

Thioamides of General formula (VI) are either commercially available or they can be obtained for example by reacting the corresponding carboxylic acid amide of the formula (V) with pentasulfide phosphorus in pyridine [R.N.Hurd, G.Delameter, Chem. Rev., 61, 45 (1961)] or with the reagent of Lawesson in toluene, pyridine, triamide hexamethylphosphoric acid [Scheibye, Pedersen and Lawesson: Bull. Soc. Chim. Beiges, 87, 229 (1978)], preferably in a mixture of tetrahydrofuran with 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone or 1,3-dimethyl-2-imidazolidinone. Hydroxyl group, an amino group or an additional carbonyl group, it is reasonable to protect by leaving a protective group, such as benzyl residue, tert-butyloxycarbonyl balance, benzyloxycarbonyl residue, respectively, by keeping the Denia, if necessary, cyclic acetal. Methods for this purpose are described, for example, in Th. W. Greene and P. G. M. Wuts "Protective Groups in Organic Synthesis", second edition, 1991, John Wiley and Sons, New York.

Thioamides of the formula (VI) receive, so that the NITRILES of General formula (IV):

enter into interaction with hydrogen sulfide (Houben-Weil, IX, 762) or thioacetamide (..Taylor, J.A.Zoltewicz, J. Am. Chem. Soc., 82, 2656 (1960)) or O,O-Diethyldithiophosphoric acid. Interaction with hydrogen sulfide is preferably carried out in an organic solvent like methanol or ethanol, interaction with thioacetamide is carried out in a solvent such as dimethylformamide, with the addition of hydrochloric acid, the interaction with O,O-Diethyldithiophosphoric acid is carried out in a solvent like ethyl acetate, in an acid, for example Hcl, conditions at room temperature or when heated.

The following examples serve to illustrate the invention without limiting, however, its scope of protection. The measured melting point or decomposition (i.e. square) are given, without amendment, and, in General, depend on the heating rate.

The compounds of formula (I) are favourable effects on fat metabolism, in particular they are suitable as anorexically funds. The compounds can be used individually or in combination with other Anor the classical biologically active substances. Such other anorexicskin biologically active substances shall be indicated, for example, in the "Roten Liste", Chapter 01, under the heading "Remedies for weight loss/reduce appetite means". Compounds suitable for the prophylaxis and, in particular, for the treatment of obesity. Connection, also suitable for the prophylaxis and, in particular, for the treatment of type II diabetes.

The effectiveness of the compounds was tested as follows.

Biological testing model.

Test anoreksighennogo action was performed on male or female mice of NMRI. After being deprived of food for 24 hours through the gastric tube was administered the test drug. When an individual content and with free access to drinking water to the animals 30 minutes after administration of the drug was offered condensed milk. Every half hour for 7 hours was determined by the consumption of condensed milk and watched the General condition of the animals. The measured consumption of milk was compared with that in the case of untreated control animals.

Table 2

Anorexically the action defined as a reduction of the cumulated consumption of milk of treated animals compared with untreated
The compound of example

Oral dose [mg/kg]Number of animals/the cumulated consumption of milk treated animals (males) N/[ml]Number of animals/the cumulated consumption of raw milk

and control animals (males) N/[ml]
The reduction of the cumulated consumption of milk in % of control
Example 1505/0,425/2,9086
Example 2505/0,345/2,9088
Example 3505/0,785/2,9073
Example 5505/0,425/4,1890
Example 6505/0,225/4,2095
Example 8505/0,285/4,2093
Example 9505/0,265/3,4693
The compound of example

Oral dose [mg/kg]Number of animals/the cumulated consumption of milk treated animals (females) N/[ml]Number of animals/the cumulated consumption of raw milk

and control animals (females) N/[ml]
The reduction of the cumulated consumption of milk in % of control
Example 10505/1,045/4,6478
Example 11505/1,345/4,6471
Example 12505/1,365/4,6471

From the table it can be seen that the compounds of formula (I) show a very good anorexically action.

Below describes in detail the receipt of some compounds of formula (I), other compounds of formula (I) are obtained in a similar manner.

Example 1 (compound 1):

6-Chloro-2-phenoxymethyl-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol

a) 2-Bromo-5-Clorinda-1-he

10 g (0.06 mol) of 5-Clorinda-1-it at room temperature and dissolved with stirring in 120 ml of glacial acetic acid. Added dropwise 0.05 ml of 48%aqueous solution Nug in water and then 3,074 ml (0.06 mol) of bromine, dissolved in 25 ml of glacial acetic acid. After stirring for 2 hours at room temperature the reaction ends (control by means of thin layer chromatography). A solution of the crude product under stirring slowly added dropwise to 300 ml of ice water. Precipitated precipitated crude product is filtered off with suction and thoroughly washed with water. The wet residue is separated of adfilter with ethyl acetate and the phases of the filtrate are separated. The organic phase is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is dissolved when heated in 120 ml of n-heptane, hot solution is filtered through a folded filter and then the solution is left to stand at a temperature of 0°for crystallization. Vegascasinoonline the product is filtered off with suction and dried in vacuum.

TPL: 94-96°C.

b) 6-Chloro-2-phenoxymethyl-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol

of 0.49 g of 2-Bromo-5-Clorinda-1-it is at room temperature, dissolved in 10 ml of anhydrous acetone and mixed with 335 mg of 2-phenoxytoluene. Stirred for 6 hours at room temperature, vegascasinoonline hydrobromide product is filtered off with suction, the residue is washed with acetone and dried in vacuum. The free base is obtained by making salt in a mixture of 30 ml of ethyl acetate and 20 ml of saturated sodium hydrogen carbonate solution and stirring for 20 minutes. The organic phase is separated, washed with a saturated solution of sodium chloride and dried over magnesium sulfate. Filtered and the filtrate concentrated in vacuo. Get 6-chloro-2-phenoxymethyl-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol with a melting point 121°C.

Example 2 (compound 6):

The hydrobromide 6-chloro-2-(2,4-dichlorphenoxy)-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol

0.25 g of 2-Bromo-5-chlorite is Dan-1-she and 0.24 g of 2-(2,4-dichlorphenoxy)thioacetamide at room temperature is dissolved in 5 ml of anhydrous acetone and stirred for 12 hours at room temperature. The precipitation is filtered off with suction, washed with acetone and dried in high vacuum. Get hydrobromide 6-chloro-2-(2,4-dichlorphenoxy)-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol with a melting point 170°C (decomposition).

Example 3 (compound 9):

2-(4-tert-Butylphenoxyacetyl)-6-chloro-8,8A-dihydroindeno-[1,2-d]thiazol-3A-ol

of 0.49 g of 2-Bromo-5-Clorinda-1-she and 0.45 g of 2-(4-tert-butylphenoxy)thioacetamide at room temperature, dissolved in 10 ml of anhydrous acetone and stirred for 12 hours at room temperature. Phase precipitate the hydrobromide is filtered off with suction and washed with acetone. The residue is suspended in a small amount of ethyl acetate and treated with a saturated solution of sodium bicarbonate. The organic phase is separated, dried over magnesium sulfate, filtered and concentrated in vacuo. Get 2-(4-tert-butylphenoxyacetyl)-6-chloro-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol with a melting point 122-124°C.

Example 4 (compound 12):

2-Benzylsulfamide-6-chloro-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol

a) 2-Benzisothiazolin

1.2 g of Benzisothiazolinone at room temperature, dissolved in 10 ml of anhydrous ethanol is mixed with 1.25 ml of diethyldithiophosphate and stirred for 6 hours while boiling under reflux. Klaeden the th reaction solution was concentrated in vacuo and purified chromatography on silica gel using a mixture of ethyl acetate and n-heptane in the ratio of 1:2. Thus obtained 2-benzisothiazolin use in the next stage.

b) 2-Benzylsulfamide-6-chloro-8,8A-dihydroindeno-[1,2-d]thiazol-3A-ol

of 0.54 g of 2-Benzylselenocyanate at room temperature, dissolved in 10 ml of anhydrous acetone, add to 0.67 g of 2-bromo-5-Clorinda-1, and it is stirred for 4 hours at room temperature. The formed precipitate is filtered off with suction, washed with acetone, treated with ethyl acetate, add a saturated solution of sodium bicarbonate and shaken twice. The organic phase is dried over magnesium sulfate, filtered and concentrated in vacuo. Get 2-benzylsulfamide-6-chloro-8,8A-dihydroindeno[1,2-d]thiazol-3A-ol with a melting point of 102-104°C.

1. The compounds of formula (I):

where

Y represents a direct bond;

X is CH2;

R1, R1', independently of one another, denote H, Cl;

R2 denotes H;

R3 denotes H;

R4 means (C8-C16-cycloalkyl; (CH2)n-A-R8, where n may indicate 1-6; and excluded group-CH2-O-CH2-phenyl, where phenyl unsubstituted;

A represents O, S;

R8 denotes methyl or (CH2)m-aryl, and m=0-6, and the aryl may mean phenyl, where the aryl part of the mod is et to be replaced by alternates in the amount of up to two, inclusive, selected from CL, O-(C1-C6)-alkyl, (C1-C6) -alkyl;

and their physiologically acceptable salts.

2. Connection under item 1 for use as a drug for prevention or treatment of obesity.

3. Connection on p. 1 in combination with at least one other anorexically biologically active substance for use as a drug for prevention or treatment of obesity.

4. The method of obtaining medicines containing one or more compounds on p. 1, characterized in that the biologically active substance is mixed with pharmaceutically suitable carrier and the mixture is brought to suitable for introduction of the form.

5. The method of obtaining compounds on p. 1, wherein according to the following reaction scheme

Base

the compound of formula (VII), where X, Y, R1, R1', R3 and R4 have the above for formula (I) values, enter into interaction with the basis for obtaining the compounds of formula (I/).



 

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The invention relates to novel polycyclic to dihydrothiazolo General formula (I), where Y is a simple bond; X is CH2; R1 is H, F, Cl, NO2, CN, COOH, (C1-C6)-alkyl, (C2-C6)-quinil, O-(C1-C6)-alkyl, and alkyl residues one, several or all of the hydrogen atoms may be replaced by fluorine; (CH2)n-phenyl, SO2-(C1-C6)-alkyl, and n = 0 and the phenyl residue up to twice may be substituted by F, Cl, CF3, OCF3, O-(C1-C6)-alkyl, (C1-C6)-alkyl; O-(CH2)n-phenyl, and n = 0 and phenyl cycle can be one - to twofold substituted by Cl, (C1-C6)-alkyl; 1 - or 2-naphthyl, 2 - or 3-thienyl; R1' is hydrogen; R2 is H, (C1-C6)-alkyl, R3 is hydrogen; R4 - (C1-C8)-alkyl, (C3-C7-cycloalkyl, (CH2)n-aryl, and n = 0-1, and aryl can be phenyl, 2-, 3 - or 4-pyridyl, 2 - or 3-thienyl, 2 - or 3-furyl, indol-3-yl, indol-5-yl, and aryl or heteroaryl residue up to twice may be substituted by F, Cl, HE, OCF3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, 2-, 3-, 4-pyridium, pyrrol-1-yl, with peregrinae ring may be substituted CF3; and their physio is

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-d - galactopyranosides -2) - 4,5-dihydrothiazolo-4 - carboxylic acid" target="_blank">

The invention relates to carbohydrates and heterocyclic compounds and in particular to a new method of obtaining-D-galactoside D-luciferin formula I

used as a substrate for the enzyme activity determination-galactosidase, which can find application in genetic engineering, enzyme analysis and DNA probes

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to new aromatic diketone derivatives of formula I

(R4, R5, R6, and R7 are independently H, OH, X-alkyl, wherein X represents oxygen; K is group of formula II

or III

;

L is group of formula IV

;

or K and L together form group of formula VI ,

wherein R1 and R3 are independently H or alkyl; R2 is H or alkyl; X1-X7 are independently O, NH; and ring "cyclus" together with carbon atom labeled with letters c and d represents anthraquinone, hydroquinone or phenyl, optionally substituted with one or more hydroxyl, alkoxyl, or alkyl groups), as well as pharmaceutically accepts salts thereof, ethers, esters, tautomers, stereomers and mixtures in any ratio. Derivatives of present invention are glucose-6-phosphatetranslocase inhibitors. Also disclosed are method for production of derivatives, pharmaceutical composition containing the same, and uses thereof as drugs, in particular for treatment of diabetes mellitus.

EFFECT: new compounds and pharmaceutical composition for treatment of diabetes mellitus.

20 cl, 4 tbl, 6 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to new (N-substitutes glycyl)-2-cyanopyrrolidines of formula I , wherein R is adamantly, substituted in 3- and/or 5-site with one or more substituents, selected from group including C1-C10-alkyl, OR1 (R1 is C1-C10-alkyl, C1-C8-alkanoyl, -CO-NR4R5, wherein R4 and R5 are independently from one another hydrogen, cyclohexyl, C1-C10-alkyl, phenyl optionally substituted with C1-C10-alkyl or C1-C10-alkoxy), in free form or in form of acid additive salt. Claimed compounds inhibit dipeptidyl-peptidase IV (DPP-IV) activity and useful in pharmaceutical composition for treatment of conditions mediated by DPP-IV, such as insulin-independent diabetes mellitus and obesity.

EFFECT: new pharmaceutical compounds inhibiting dipeptidyl-peptidase IV.

5 cl, 1 dwg, 4 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with insulin preparations applied in therapy of diabetes mellitus. This innovation could be applied in medicinal industry for insulin manufacturing. To obtain insulin one should apply reindeer's pancreas to be homogenized in solution of hydrochloric acid ethanol followed by extraction with subsequent clarification of solution and obtaining the supernatant which then should undergo ion-exchange chromatography and isoelectric deposition by obtaining insulin. The latter should be purified due to high-performance reversed-phase liquid chromatography. Insulin obtained is competitive for the bond with insulin receptor at concentration of above 100 ng/ml due to causing high increase of receptor binding, moreover, it has higher hydrophoby against standard insulins, thus, it has certain differences in the structure of its molecule.

EFFECT: higher efficiency of insulin manufacturing.

2 cl, 2 dwg, 2 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new compound: N-[2-hydroxy-3(1-piperidinyl)-propoxy]-pyridine-1-oxyde-3-carboxyimidoyl chloride, stereoisomers thereof acid additional salts useful in treatment of pathological insulin resistance.

EFFECT: new compound useful in medicine.

5 cl, 10 tbl, 10 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new 2-aminopyridine derivatives of formula I , wherein R1 is cyano, carboxyl or carbamoyl; R2 is hydrogen, hydroxyl, C1-C6-alkoxy or phenyl; R3 and R4 are aromatic hydrocarbon such as phenyl or naphthyl, 5-14-membered 5-14-membered optionally substituted aromatic group, excepted cases, when (1) R1 is cyano, R2 is hydrogen, and R3 and R4 are simultaneously phenyl;(2) R1 is cyano, R2 is hydrogen, R3 is 4-pyridyl, and R4 is 1-pyridyl; (3) R1 is cyano, R2 is 4-methylphenyl, and R3 and R4 are simultaneously phenyl;(4) R1 is cyano, R2, R3 and R4 are simultaneously phenyl, or salts thereof. Derivatives of present invention have adenosine receptor antagonist activity and are useful in medicine for treatment of irritable bowel syndrome, constipation, and defecation stimulation.

EFFECT: 2-aminopyridine derivatives as adenosine receptor antagonists useful in medicine.

34 cl, 2 tbl, 179 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a form with reduced size of particles of the compound (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid described by the formula (I)

or its pharmaceutically acceptable salt or any solvate. Above said compound is useful in treatment of metabolic disorders, such as insulin resistance syndrome determined as reduced sensitivity to insulin effect. Also, invention relates to pharmaceutical compositions containing form with reduced size of particles of this compound or its pharmaceutically acceptable salt or their solvate as an active component, and to methods for preparing form with reduced size of particles of this compound or its pharmaceutically acceptable salt.

EFFECT: improved preparing methods, valuable medicinal properties of compound.

12 cl, 5 ex

FIELD: medicine, cardiology, endocrinology.

SUBSTANCE: invention proposes applying false flax plant oil as a hypoglycemic agent and agent that exerts the normalizing effect on lipid fraction of alpha-lipoproteins (high density lipoproteins; HDLP) and used in treatment of cardiovascular and endocrine diseases, and a method for it applying. This agent is known early as an antioxidant and a hypolipidemic preparation. Detection of new properties allows expanding application of this agent in clinics for treatment of patients with heart ischemic disease, stenocardia, hypertension and diabetes mellitus. The preparation reduces risk for development of atherosclerosis and allows significant reducing doses of basic drugs.

EFFECT: valuable medicinal properties of agent, enhanced effectiveness of treatment.

4 cl, 6 ex

FIELD: organic chemistry, biochemistry, medicine, endocrinology.

SUBSTANCE: invention relates to a trans-olefinic activator of glucokinase representing compound taken among the group consisting of olefinic amide of the formula (I): wherein R1 and R2 mean independently of one another hydrogen, halogen atom, nitro-group, perfluoro-(lower)-alkyl, (lower)-alkylsulfonyl or (lower)-alkylsulfonylmethyl; R means -(CH2)m-R3 or lower alkyl comprising from 2 to 4 carbon atoms; R3 means cycloalkyl comprising from 3 to 8 carbon atoms; R4 means the group: or unsubstituted, or monosubstituted five- or six-membered heteroaromatic ring linked by ring carbon atom with indicated amino-group wherein this five- or six-membered heteroaromatic ring comprises from 1 to 2 heteroatoms taken among the group consisting of sulfur or nitrogen atom wherein one heteroatom being as nitrogen atom is arranged near with binding ring carbon atom, and wherein indicated monosubstituted heteroaromatic ring is substituted at ring carbon atom not adjacent with mentioned binding carbon atom with a substitute taken among the group consisting of halogen atom and group of the formula: m = 0 or 1; n = 0, 1, 2, 3 or 4; R7 means hydrogen atom or lower alkyl; Δ means trans-configuration relatively to a double bond; or its pharmaceutically acceptable salt. Also, invention relates to pharmaceutical composition, method for prophylactic or therapeutic treatment of diabetes mellitus of type II and to methods for preparing compounds of the formula (I). Invention provides preparing activators of glucokinase that enhance insulin secretion in treatment of diabetes mellitus of type II.

EFFECT: valuable medicinal properties of compounds.

25 cl, 29 ex

FIELD: pharmaceutical agents, in particular glyburide containing composition.

SUBSTANCE: claimed composition contains 5-chloro-N-[2-[4-[[(cyclohexylamino) carbonyl]amino]sulfonyl]ethyl]-2-methoxybenzamide, known under generic name as glyburide, and has the next grain-size classification (%): undersize of 3-11 mum - 25; undersize of 6-23 mum - 50 %, and undersize of 15-46 mum - 75 %. Such grain-size classification affords the ability to increase glyburide dissolution rate and provide reproducible biological availability of glyburide.

EFFECT: pharmaceutical composition useful for treatment of II- type diabetes.

11 cl, 2 tbl, 6 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of benzimidazole represented by the following formula (I) or its salt:

wherein R1 represents (lower)-alkyl group; R2 represents aromatic (lower)-alkyl group that can be substituted with one or more groups taken among halogen atom, alkyl group, halogen-(lower)-alkyl group, nitro-group, aromatic group, aromatic (lower)-alkoxy-group, (lower)-cycloalkyloxy-(lower)-alkyl group, aromatic (lower)-alkyl group, aromatic (lower)-alkenyl group, aromatic (lower)-alkynyl group, aromatic oxy-(lower)-alkyl group, (lower)-cycloalkyl-(lower)-alkoxy-group, alkenyl group, (lower)-alkoxy-group, (lower)-alkylthio-group and (lower)-alkanesulfonylcarbamoyl group; R3 represents alkyl group, hydroxy-(lower)-alkyl group, alkenyl group, aromatic group, halogenated aromatic group, (lower)-alkyl aromatic group, (lower)-alkenyl aromatic group or aromatic (lower)-alkenyl group; -X- represents cross-linking group represented by one of the following formulas: (II) , (III) , (IV) , (V) . Also, invention relates to pharmaceutical compositions eliciting activity that reduces blood glucose level based on this compound. Invention provides preparing new compounds and pharmaceutical compositions based on thereof used for prophylaxis and treatment of damaged tolerance to glucose, diabetes mellitus, insulin-resistance syndrome, vascular failures syndrome, hyperlipidemia and cardiovascular disorders.

EFFECT: valuable medicinal properties of compounds and compositions.

16 cl, 1 tbl, 86 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention represents ligands MC-4 and/or MC-3 of the formula (I): , wherein X means hydrogen atom, -OR1, -NR1R1' and -CHR1R1' wherein R1 and R1' are taken among the group: hydrogen atom, (C1-C6)-alkyl and acyl; (1) each R2 is taken independently among the group: hydrogen atom, (C1-C6)-alkyl; or (2) (a) R2 bound with carbon atom that is bound with X and Z1 and substitute R5 can be optionally bound to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; or (b) R2 bound with carbon atom that is bound with ring Ar can be bound with R7 to form ring condensed with ring Ar; each among Z1, Z2 and Z3 is taken independently from the following groups: -N(R3e)C(R3)(R3a)-, -C(R3)(R3a)N(R3e)-, -C(O)N(R3d)-, -N(R3d)C(O)-, -C(R3)(R3a)C(R3b)(R3c)-, -SO2N(R3d)- and -N(R3d)SO2- wherein each among R3, R3a, R3b and R3c, R3d, R3e when presents is taken independently among hydrogen atom and (C1-C6)-alkyl; p is a whole number from 0 to 5 wherein when p above 0 then R4 and R4' are taken among hydrogen atom, (C1-C6)-alkyl and aryl; R5 represents 5 substitutes in phenyl ring J wherein each R5 is taken among hydrogen atom, hydroxy-, halogen atom, thiol, -OR12, -N(R12)(R12'), (C1-C6)-alkyl, nitro-, aryl wherein R12 and R12' are taken among hydrogen atom and (C1-C6)-alkyl; or two substitutes R5 can be bound optionally to form carbocyclic or heterocyclic ring that is condensed with phenyl ring J; q = 0, 1, 2, 3, 4 or 5 wherein when q above 0 then R6 and R6' are taken among hydrogen atom and (C1-C6)-alkyl; Ar is taken among the group consisting of phenyl, thiophene, furan, oxazole, thiazole, pyrrole and pyridine; R7 are substitutes at ring Ar wherein each R7 is taken among hydrogen, halogen atom, -NR13R13', (C1-C6)-alkyl and nitro- wherein R13 and R13' are taken among hydrogen atom and (C1-C6)-alkyl; r is a whole number from 0 to 7 wherein when r is above 0 then R8 and R8' are taken among hydrogen atom and (C1-C6)-alkyl; B is taken among -N(R14)C(=NR15)NR16R17, -NR20R21, heteroaryl ring and heterocycloalkyl ring wherein R14-R17, R20 and R21 are taken independently among hydrogen atom and (C1-C6)-alkyl; s = 0, 1, 2, 3, 4 or 5 wherein when s is above 0 then R and R9' are taken among hydrogen atom and (C1-C6)-alkyl; R10 is taken among the group consisting of optionally substituted bicyclic aryl ring and optionally substituted bicyclic heteroaryl ring; D is taken among hydrogen atom, amino- and -C(O)R11 wherein R11 is taken among the following group: hydroxy-, alkoxy-, amino-, alkylamino-, -N(R19)CH2C(O)NH2 wherein R19 represents (C1-C6)-alkyl, -NHCH2CH2OH and -N(CH3)CH2CH2OH, or its isomers, salts, hydrates or biohydrolysable ester, amide or imide.

EFFECT: valuable medicinal properties of compounds.

18 cl, 107 ex

FIELD: improved method for oil production.

SUBSTANCE: target oil, enriched in HODE, or esters thereof is obtained by controlled oxidation of linoleic acid and/or linolenic acid or esters thereof in presence of oxidation catalyst. Oxidation is stopped when total HODE or ester content is more than 5 %, and/or content of isomeric 9-hydroxy-10,12-octadecadienic acid (9-HODE) or esters thereof is more than 1,5 %; and hydroperoxides formed in oxidation process are reduced with reducing agent in presence of antioxidant. Invention is also relates to oil enriched in 9-HODE or esters or salts thereof having an lipolytic action; to drug or food additive for obesity treatment; cosmetic for local treatment of cellulite. Compound for controlling of adipocyte lipolytic activity and hydrolysis of triglycerides accumulated in adipocytes is also disclosed.

EFFECT: novel pharmaceutical composition for obesity treatment.

11 cl, 1 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention describes a method for prophylaxis or treatment of states that involves inhibition of activity of enzyme that catalyzes hydrolysis of ester functional groups and wherein indicated state represents obesity or accompanying disorder, and wherein compound of the formula (1):

is prescribed, or its pharmaceutically acceptable salt, ester, amide or a precursor. Also, invention relates to a method for manufacturing the medicinal preparation used for prophylaxis or treatment of states wherein inhibition of activity of enzyme is required wherein indicated enzyme catalyzes hydrolysis of ester functional groups. In the formula (1) A means a 6-membered aromatic or heteroaromatic ring; R1 means a branched or unbranched alkyl (its carbon chain can be broken by one or more oxygen atoms), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, reduced aryl, reduced heteroaryl, reduced heteroarylalkyl or their substituted derivative wherein a substitute is taken independently among the following group: halogen atom, alkyl, alkyl substituted with halogen atom, aryl, arylalkyl, heteroaryl, reduced heteroaryl, reduced heteroarylalkyl, arylalkoxy-, cyano-, nitro-group, -C(O)R4, -CO2R4, -SOR4, -SO2R4, -NR6R7, -OR6, -SR6, -C(O)CX1X2NR6R7, -C(O)NR4R5, -C(O)N(OR5)R6, -NR6C(O)R4, -CR6(NH2)CO2R6, -NCX1X2CO2R6, -N(OH)C(O)NR6R7, -N(OH)C(O)R4, -NHC(O)NR6R7, -C(O)NHNR6R7, -C(O)N(OR5)R6 or lipid, or steroid (natural or synthetic) under condition that any substituting heteroatom in R1 or R2 must be separated from exocyclic nitrogen atom by at least two carbon atoms (preferably, saturated atoms), and wherein R4 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl, OR6, NHCX1X2CO2R6 or NR6R7; R5 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl; R6 and R7 are taken independently among hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylalkyl, reduced heteroarylalkyl or -(CH2)n(OR5)m wherein n = from 1 to 12, preferably, from 2 to 10; m = from 1 to 3; R5 means preferably (C2-C10)-alkyl; X1 and X2 represent independently hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylalkyl or reduced heteroarylalkyl. Also, invention describes compound of formulae (II), (IIa) and (IIb) given in the description and a method for preparing compound of formulae (II), (IIa) and (IIb), pharmaceutical composition used for prophylaxis or treatment of obesity and/or accompanying disorder, nutrition product, a method for prophylaxis or treatment of obesity or accompanying disorders, a method for inhibition of activity of enzymes, a method for reducing fat content in animals, a cosmetic method for maintaining this weight and a new intermediate compound of the formula (IV) indicated in the description. Invention discloses the possibility for prophylaxis or treatment of obesity or accompanying disorders.

EFFECT: valuable medicinal properties of compounds.

33 cl, 1 dwg, 2 tbl, 5 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention describes a method for prophylaxis or treatment of states wherein inhibition of enzyme activity is required wherein this enzyme catalyzes hydrolysis reaction of ester functional groups and wherein indicated disorder represents obesity or accompanying disease. Method involves prescribing compound of the formula (1):

or its pharmaceutically acceptable salt, ester, amide or precursor wherein in the formula (1) a means six-membered aromatic or heteroaromatic ring; R1 means a branched or unbranched alkyl (its carbon chain can be broken possibly by one or more oxygen atoms), alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, reduced aryl, reduced heteroaryl, reduced heteroarylalkyl or their substituted derivative wherein a substitute represents one or more group taken independently among the following group: halogen atom, alkyl, halogen-substituted alkyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, reduced heteroarylalkyl, arylalkoxy-, cyano-, -C(O)R4, -CO2R4, -SOR4, -SO2R4, -NR6R7, -OR6, -SR6, -C(O)CX1X2NR6R7, -C(O)NR4R5, -C(O)N(OR5)R6, -NR6C(O)R4, -CR6(NH2)CO2R6, -NCX1X2CO2R6, -N(OH)C(O)NR6R7, -N(OH)C(O)R4, -NHC(O)NR6R7, -C(O)NHNR6R7, -C(O)N(OR5)R6, or lipid or steroid (natural or synthetic one) under condition that any substituting heteroatom in R1 or R2 must be segregated from nitrogen exocyclic atom by at least two carbon atoms (preferably, saturated ones); R2 means hydrogen atom or group, such as determined for R1 and wherein R4 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl, OR6, NHCX1X2CO2R6 or NR6R7; R5 represents hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, reduced heteroaryl or reduced heteroarylalkyl; R6 and R7 are taken independently among hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylakyl, reduced heteroarylalkyl or -(CH2)n(OR5)m wherein n = from 1 to 12 but preferably from 2 to 10; m = from 1 to 3; for R5 (C2-C10)-alkyl is preferable; X1 and X2 represent independently hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, reduced heteroaryl, heteroarylalkyl or reduced heteroarylalkyl. Also, invention describes compounds of formulas (II), (IIa), (IIb) given in the invention description, method for preparing compound of the formula (II), pharmaceutical composition used for prophylaxis or treatment of obesity or accompanying disorder, the nutrition foodstuff, method for prophylaxis or treatment of obesity or accompanying disorders, method for inhibition of enzymes activity, method for reducing the fat content in animals, cosmetic method for maintaining this weight of animals. Invention discloses the possibility for prophylaxis or treatment of obesity or accompanying disorders.

EFFECT: valuable medicinal properties of compounds.

30 cl, 1 dwg, 2 tbl, 5 ex

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