Derivative imidazo(1,2-b)benzothiazole as antagonists of benzodiazepines

 

(57) Abstract:

The essence of the invention: derivatives of imidazo (1,2 - b)benzothiazole F. - ly (1), where R1- cyclopropyl, R2and R3taken together mean a group of f - crystals 2 and f - crystals 3, where X1and X2- same or different and each means a hydrogen atom, a C1-C5-alkyl, Allakaket, normal or branched C1-C5- alkoxy, or X1and X2taken together mean a group of methylendioxy, as antagonists of benzodiazepines. table 2. f - crystals 1, 2, 3, respectively:

The invention relates to a new imidazo[1,2-b]benzothiazole General formula

where R1- cyclopropyl, R2and R3taken together, mean group

where X1and X2the same or different, each signifies a hydrogen atom alkyl WITH1-C5, normal or branched alkoxy WITH1-C5Allakaket, or X1and X2taken together mean a group of methylendioxy, which are antagonists of benzodiazepines.

Known structural analogue of the proposed compounds having the same biological activity (see EP 27214).

The purpose of the invention is to develop new compounds, HHS goal is achieved by the proposed method of obtaining compounds of General formula 1, namely, the compound of formula II

NH2where R2and R3above, is subjected to the interaction with 3-bromo-1-hydroxypropan-2-one to obtain the compounds of formula III

where the values of R2and R3above, which are oxidized by manganese dioxide to obtain the compounds of formula IV

where R2and R3above, the compound obtained is subjected to interaction with the compound of the formula V

R, Mg-Hal, where Hal is chlorine atom, bromine or iodine, R1as mentioned above, to obtain compounds of formula VI:

where R1, R2, R3above, which are oxidized with the release of the target product.

7-Methoxy-imidazo/2,1-b) benzothiazole-2-carboxaldehyde.

a) 7-Methoxy-imidazo/2,1-b) benzothiazole-2-methanol.

In a nitrogen atmosphere at 80aboutC for 3 h and stirred 11.6 g 0,69 mole of 2-amino-5-methoxybenzothiazole and 3-bromo-1-hydroxypropan-2-she (11.6 g 0,076 mol) in anhydrous tetrahydrofuran (120 ml). The mixture is cooled on ice and the surface layer was dementiava. The residue is heated in 60 ml of ethanol for 1 h, cooled and filtered to obtain 7-methoxyimino/2,1-b) benzothiazole-2-methanol ether Hydrobromic acid in the form of a solid ve is stragiht 5 x 200 ml of chloroform. The extracts are dried, evaporated and dissolved in diethyl ether. Get 6,30 g 42%, so pl. 202-5about(Eton) 7-methoxy-imidazo/2,1-b) benzothiazole-2-methanol as colorless crystals.

Calculated, %: C 56,50; N 4,30; N 11,96.

WITH11H10N2ABOUT2S

Found, %: C 56,32; N 4,36; N 11,93; S 13,69.

b) 7-Methoxy-imidazo/2,1-b) benzothiazole-2-carboxaldehyde.

5.0 g 0,0225 mole of 7-methoxy-imidazo/2,1-b) benzothiazole-2 - methane and 10 g, 0,115 mole of manganese dioxide, boiled in chloroform (500 ml) for 2 hours In a hot condition, the mixture is filtered and evaporated to obtain to 3.92 g 79% , colorless crystals, etc. = 214-5aboutC, 7-methoxy-imidazo/2,1-b) benzothiazole-2-carboxaldehyde - Yes (Eton).

Calculated, %: 56,89; H 3,47; N 12,96; S 13,80.

WITH11H8ABOUT2N2S

Found, %: C 56,79; N. Of 3.56, N 12,08; S Of 13.75.

P R I m e R 1. (7-Methoxy-imidazo/2,1-b) benzothiazole-2-yl)cyclopropylmethanol.

Stage A: (7-methoxy-imidazo/2,1-b) benzothiazole-2-yl) cyclopropyl methanol.

Prepared from 3.6 g of 0.03 M cyclopropylamine and 0.8 g 0,033 M magnesium in 50 ml of anhydrous tetrahydrofuran, cyclopropylboronic magnesium is added drop by drop to a suspension of 3.9 g 0,0177 M, 7-methoxy-imidazo/2,1-b/benzoate 3 h and cooled saturated aqueous ammonium chloride. The mixture is extracted with ethyl acetic acid and the extracts dried and evaporated under reduced pressure. The remainder chromatographic on silica gel, elwira 2% methanol/dichloromethane.

Get 2,75 g 69% (7-methoxy-imidazo/2,1-b) benzothiazole-2-yl) cyclopropyl methane in the form of a colorless solid substance, so pl. = 151-3about(Eton).

Calculated, %: C 61,30; N 5,14; N Of 10.21; S Of 11.69.

WITH14H14N2ABOUT2S.

Found, %: C 61,17; N 5,23; N 10,24; S 11,48.

Stage B: (7-methoxy-imidazo/2,1-b) benzothiazole-2-yl) cyclopropyl mechanon.

Stirred at the boil for 1 hour, the mixture of 1.63 g 0,0062 M, 7-methoxy-imidazo/2,1-b) benzothiazole-2-yl)cyclopropyl of methanol and 4.8 g, to 0.055 M, manganese dioxide in 300 ml of chloroform. The mixture is then filtered while hot and evaporated. Obtain 1.45 g 89% (7-methoxy-imidazo/2,1-b) benzothiazole-2-yl)cyclopropyl methanol as a colourless solid, melting at 213 - 4about(Eton).

Calculated, %: C 61,75; N. Of 4.44; N 10,29; S 11,77.

C14H12N2O2< / BR>
Found, %: C 62,01; N. Of 4.49; N 10,32; S 11,76.

P R I m e R s 2-8. Using the method of example 1, but from the corresponding compounds of formula V, where R2and R3matter, the criminal code is Alisov, are given in table.1.

6-Methoxy-imidazo/2,1-b) benzothiazole-2-methanol used in example 3 (compound of formula (VII), was obtained as described below.

Preparation B: 6-methoxy-imidazo/2,1-b) benzothiazole-2-methanol.

4 g of ethyl ester imidazo/2,1-b) benzothiazole-2-carboxylic acid in anhydrous tetrahydrofuran is stirred with 1.5 g of lithium borohydride 48 h at room temperature in a dry nitrogen. The mixture was then treated with excess 2n. hydrochloric acid and heated at 50aboutC for 2 h to decompose the complex. The mixture is converted into a base with an aqueous solution of sodium bicarbonate and extracted with ethyl ester of acetic acid. The extract is dried with magnesium sulfate and evaporated to dryness under reduced pressure to obtain with 3.27 g, 96.4% of 6-methoxy-imidazo/2,1-b) benzothiazole-2-methanol as a colourless solid. So pl. = 189-90about(Eton).

Calculated, %: 56,40; N 4,30; N 11,96; S 13,69.

WITH11H10N2ABOUT2S

Found, %: 56,37; N. Of 4.38; N 11,90; S 13,65.

P R I m e R 9. There were prepared tablets according to the following recipe:

The compound of example 1 20 mg

Excipient for one

tablets 150 mg

(Detail excipient: Lactose, starch, Thalia example 4 20 mg

Experient for one

tablets 150 mg

(Detail excipient: Lactose, starch, talc, magnesium stearate).

Biochemical activity.

Means acting began to benzodiazepine receptors was measured using the connection flunitrazepam, radioactively labeled (3N).

The values given in the table.2 are the concentrations (mol x 10-9) of the studied compounds, which inhibit by 50% the specific connection 0.6 x 10-9flunitrazepam marked3N, in the preparation of films, taken from the back of the rat brain (the value of the IC50).

We studied the activity of the known compounds of formula

< / BR>
Connection As described in the European patent N 0.027.214, and exhibiting properties similar to the properties obtained in the application of products.

In the test for means to receptor benzodiazepibe, product And shows the value J50equal to 2500 THEM. Thus, when comparing this value with the results of the claimed compounds, the latter exhibit much higher activity.

Derivative imidazo (1,2-b)benzothiazole General formula

< / BR>
where R1- cyclopropyl;

R2and R3VM is, normal or branched C1- C5-alkoxy, Allakaket or X1and X2together - group methylendioxy,

as antagonists of benzodiazepines.

 

Same patents:

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention describes compound of the general formula (3): wherein R15 represents a heterocyclic group chosen from 3-7-membered saturated or 4,7-membered unsaturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom, or 7-14-membered polycyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R16 represents a cycloalkyl group comprising 3-7 carbon atoms, monocyclic aromatic hydrocarbon group comprising 6-14 carbon atoms, or heterocyclic group chosen from 3-7-membered saturated or 4-7-membered unsaturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R17 represents a monocyclic aromatic hydrocarbon group comprising 6-14 carbon atoms or heterocyclic group chosen from 4-7-membered saturated monocyclic heterocyclic group comprising 1-4 atoms chosen from nitrogen atom, oxygen atom and sulfur atom that can comprises a substitute; R18 represents hydrogen atom or (C1-C)-alkyl group; X represents -S-, -SO- or -SO2; or N-oxide or S-oxide of this compound; their salt; or solvate of above described compound. Proposed compounds possess the inhibitory activity against producing/secretion of β-amyloid protein and can be used in treatment of such diseases as Alzheimer's disease, Down's disease and other diseases associated with amyloid deposition.

EFFECT: valuable medicinal properties of inhibitors.

7 cl, 1 tbl, 410 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to compounds of the formula: , wherein variable value Y in ring is not obligatory and represents heteroatom chosen from nitrogen (N), oxygen (O) and sulfur (S) atoms under condition that N atom is trivalent and O or S atoms are bivalent; k means a whole number from 0 to 1; n means a whole number 0, 1 or 2; p means a whole number 0, 1 or 2; X means O or S atom; dotted lines represent a bond or its absence under condition that ring comprises only a single double bond and two adjoining lines are not a bond; R1, R2, R3 and R represent independently hydrogen atom (H), phenyl wherein indicated phenyl group is substituted optionally with one, two or three substitutes represented by (C1-C6)-alkyl, -SO3H, -N3, halogen atom, -CN, -NO2, -NH2, (C1-C6)-alkoxy-, (C1-C6)-thioalkoxy-, (C1-C6)-alkylamino-, (C1-C6)-dialkylamino-group, (C2-C6)-alkynyl, (C2-C6)-alkenyl; 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms wherein indicated heteroaryl groups are substituted optionally and independently with one, two or three substitutes represented by (C1-C6)-alkyl, -SO3H, -N3, halogen atom, -CN, -NO2, -NH2, (C1-C6)-alkoxy- (C1-C6)-thioalkoxy-, (C1-C6)-alkylamino-, (C1-C6)-dialkylamino-group, (C2-C6)-alkynyl, (C2-C6)-alkenyl, or indicated groups R1, R2, R3 and R4 represent independently alkyl comprising from 1 to 4 carbon atoms, cycloalkyl comprising from 3 to 5 carbon atoms, -CH2CN, -CH2SR5, -CH2NR6R6, -COR5, -CH2OR5, -OR6, -SR6, -NR6R6, alkenyl comprising from 1 to 4 carbon atoms, alkynyl comprising from 1 to 4 carbon atoms, cycloalkyl comprising from 3 to 6 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom, -CF3 or -CN, oxygen atom bound by a double bond with ring carbon under condition that adjoining dotted line inside of ring means absence of a bond; R5 means H, -OR7, alkyl comprising from 1 to 4 carbon atoms, -CF3, cycloalkyl comprising from 3 to 6 carbon atoms, phenyl, phenyl substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF3, either R5 represents 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms, and 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atoms, bromine atom, iodine atom or -CF3; R6 means H, alkyl comprising from 1 to 4 carbon atoms, allyl, cycloalkyl comprising from 3 to 6 carbon atoms, phenyl, phenyl substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF3, either R6 represents 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms, either 5- or 6-membered heteroaryl comprising from 1 to 3 heteroatoms chosen from O, S and N atoms substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF3; R7 means H, alkyl comprising from 1 to 4 carbon atoms, allyl, cycloalkyl comprising from 3 to 6 carbon atoms, phenyl, phenyl substituted with one or two alkyl groups comprising from 1 to 4 carbon atoms, fluorine atom, chlorine atom, bromine atom, iodine atom or -CF3; R1 and R2 or R2 and R3, or R3 and R4 can form in common a ring with corresponding carbon atoms to which they are bound; fragments represented by substitutes R1 and R2 or R2 and R3, or R3 and R4 have the following formulae (i): , (ii): , (iii): , (iv): or (v): - wherein m means a whole number from 0 to 3; R8 represents independently H, alkyl comprising from 1 to 6 carbon atoms, alkenyl comprising from 2 to 6 carbon atoms, alkynyl comprising from 2 to 6 carbon atoms, -SO3H, -N3, -CN, - NO2, F, Cl, Br, J atoms, -CF3, -COR9, -CH2OR9, -OR10, -SR10, (C1-C)-alkylamino- or (C1-C6)-dialkylamino-group wherein R9 means H, alkyl comprising from 1 to 6 carbon atoms, or -OR10 wherein R10 represents independently H or alkyl comprising from 1 to 6 carbon atoms. Also, invention relates to compounds of the formula: and , and to a method for activation of alpha2B- or alpha2C-adrenergic receptors. Invention provides synthesis of novel biologically active compound possessing activity as agonists of alpha-2B and alpha-2C-adrenergic receptors.

EFFECT: valuable medicinal properties of compounds.

34 cl, 5 tbl, 33 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the compound of formula I: , where R1, R2 and R3 are equal or different and represent hydrogen, halogen, alkyl, aloxy, hydroxyl, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group, R4 represents hydrogen, alkyl or alkylaryl group; X represents CH2, oxygen atom and sulphur atom; n represents 2 or 3, and individual (R)- and (S)-enantiomers or the mixture of enantiomers and its pharmaceutically acceptable salts; where alkyl termine denotes straight and branched hydrocarbon chains, containing fro one to six atoms of carbon, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups, termine aryl denotes phenyl or naphtyl group, optionally substituted alkyloxy group, halogen or nitro group, termine halogen denotes fluorine, chlorine, bromine or iodine. The compounds have valuable pharmaceutical properties and perspectives for the treatment of cardiovascular disorder, such as hypertension and chronic heart failure. The method of production of individual (R)- and (S)-enantiomers or the mixture of enantiomers and pharmaceutically acceptable salts of the compound of formula I, pharmaceutical composition having inhibitor dophamine-β-hydrolaze potency, containing therapeutic effective volume of the compound of formula I, different variants of formula I compound application and intermediate compounds are described.

EFFECT: production of new compounds, imidazole derivatives having useful biological properties.

21 cl, 2 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to α-2A/α-1A selective agonist, which is a compound with formula , as well as to a pharmaceutical composition, which contains a pharmaceutical carrier and a therapeutic effective quantity of α-2A/α-1A selective agonist, which contains a compound with structure 1.

EFFECT: obtaining selective agonist which can be used for preventing or alleviating neurological conditions without an accompanying sedative effect during extraneous administration.

6 cl, 2 tbl, 2 ex, 2 dwg

FIELD: chemistry.

SUBSTANCE: present invention pertains to a malononitrile compound with formula (I): where one of X1, X2, X3 and X4 stands for CR100, where R100 is a group with formula (II) each three of the other X1, X2, X3 and X4 is nitrogen or CR5, under the condition that, from one to three of X1, X2, X3 and X4 stands for nitrogen, Z is oxygen, sulphur or NR6. The malononitrile compound can be used a pesticide in agriculture.

EFFECT: obtaining a new pest control compound and its use as an active ingredient of a pesticide composition.

18 cl, 180 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention can be used for treating or preventing diseases and conditions, mediated by peroxisome proliferator activated gamma receptor (PPARγ). In formula (I) W represents a COOH group or -COOC-C1-C4alkyl; Y represents NH; Z represents S or O; X represents O; R1-R6 each independently represents a hydrogen atom or substitute, chosen from a group consisting of: C1-C4-alkyl, thienyl or phenyl, where phenyl is optionally substituted with one or more substitutes, independently chosen from a group consisting of C1-C4-alkyl, C1-C4-alkoxy, a halogen atom; -NO2 and -CN; A represents C1-C4-alkyl, -N(C1-C4-alkyl)-CO-C3-C7-cycloalkyl, aryl, chosen from a group consisting of phenyl, naphthyl, or heteroaryl, chosen from a group consisting of oxazolyl, isoxazolyl, thienyl, pyridyl, thiazolyl, thiadiazolyl, benzo[b]thienyl, imidazolyl, indolyl and carbazolyl, where aryl and heteroaryl are substituted or not substituted with one or more substitutes, independently chosen from a group consisting of C1-C4-alkyl, C1-C4-alkoxy, phenyl and a halogen atom; and n is an integer from 0 to 4. The invention also relates to a pharmaceutical composition, containing the invented compound as an active component, use of the compounds to make a medicinal agent, and method of treatment.

EFFECT: obtaining new biologically active compounds.

22 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel hexafluoroisopropanol substituted derivatives of cyclohexane of formula (I) with LXRα- and/or LXRβ agonist modulation properties, as well as to their pharmaceutically acceptable salts. In formula (I) R1 denotes hydrogen, lower alkyl, fluoro-lower alkyl, lower alkyl-carbonyl, fluoro-lower alkyl-carbonyl, phenyl-lower alkyl, C3-C6-cycloalkyl-lower alkyl, C3-C6-cycloalkylcarbonyl or C3-C6-cycloalkyl-lower alkyl-carbonyl; R2 denotes hydrogen or lower alkyl; R3 denotes lower alkyl, phenyl-lower alkyl, where phenyl is possibly substituted with lower alkoxycarbonyl, lower alkoxycarbonyl, or if X represents a single bond and m is not equal to 0, R3 can also denote a hydroxy group; R4 denotes phenyl or heterocyclyl, where heterocyclyl is a five-member aromatic heterocyclic ring containing two heteroatoms selected from nitrogen and sulphur, optionally substituted with 1-3 substitutes independently selected from a group which includes lower alkyl and halogen; X denotes a single bond, SO2, CO or C(O)O; m equals 0, 1, 2 or 3; n equals 0 or 1. The invention also relates to a pharmaceutical composition containing formula (I) compounds.

EFFECT: novel compounds have useful biological properties.

20 cl, 35 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula

where R1 independently represents H, alkyl containing 1-4 carbon atoms, p represents an integer selected from 0 and 2, R3 is independently selected from a group consisting of fluoro-substituted alkyl containing 1-4 carbon atoms, F, Cl.

EFFECT: compounds are useful as medicine for mammals, including humans, for treating diseases and relieving conditions which respond to treatment by agonists of alpha2 adrenergic receptors.

12 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new imidazole derivatives of general formula I , where R1 is C1-C10alkyl or C3-C10cycloalkyl, each possibly and independently substituted with 1 substitute selected from C3-C10cycloalkyl or aryl or a heteroaryl group, possibly substituted with one or two halogens; aryl or heteroaryl; R2 is C1-C10alkoxy or C1-C10thioalkyl; R3 is C1-C10alkoxy, possibly substituted with one C1-C10alkoxy or nitrile, where the said alkoxy group can be cyclic or can contain one O heteroatom; R4 is C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or C3-C10cycloalkyl, each possibly and independently substituted with 1 or 2 substitutes selected from C1-C10alkoxy, C3-C10cycloalkyl, carboxylic ester, or with one or two aryl or heteroaryl groups, possibly substituted with one substitute selected from C1-C10alkyl, C3-C10cycloalkyl, nitro or halogen; aryl or heteroaryl, each possibly and independently substituted with 1-3 substitutes selected from C1-C10alkyl, C3-C10cycloalkyl, C1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, nitrile or aryl group, possibly substituted with one halogen; where up to three hydrogen atoms of the alkyl group can be substituted with fluorine atoms; where the said cycloalkyl can independently have one or two carbon atoms substituted with O or N; where the said aryl denotes an aromatic ring having 6 to 10 carbon atoms, including mono- and bicyclic compounds; and where the said heteroaryl denotes an aromatic ring having 3 to 10 carbon atoms, including mono- and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulphur atoms; except compounds given in paragraph 1. The invention also pertains to use of the said compounds for making a medicinal agent, a treatment and prevention method, a compound of formula II (values of radicals are given in the formula of invention).

EFFECT: new imidazole derivatives having positive allosteric modulator effect on GABAB receptor are obtained.

30 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described a compound of formula I: or its pharmaceutically acceptable salt, where R2 represents (CR3R4)n-NR5R6 and m, p, q, Ar, R1, R3, R4, R5 and R6 are those as specified in the patent claim and defined as selective 5-NT6 and/or 5-NT2A antagonists. There is also described a pharmaceutical composition containing this compound, and application thereof in preparing drugs for treating diseased conditions of central nervous system chosen from psychoses, schizophrenia, manic depressions, neural disorders, memory impairment, attention deficient syndrome, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, malnutrition and Huntington's disease.

EFFECT: preparation of the compounds which can find application in treatment of a diseased condition of central nervous system.

27 cl, 1 tbl, 29 ex

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

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to polycyclic dihydrothiazoles and their physiologically acceptable salts and physiologically functional derivatives. Invention describes compounds of the formula (I): wherein r1 and R1' mean independently of one another atoms H, F, Cl, Br and J; R2 means hydrogen atom (H); R3 means chlorine (Cl), bromine (Br) atom; R4 means phenyl, and a method for their preparing. Compounds can be used, for example, as anorectics for prophylaxis or obesity treatment.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

5 cl, 2 tbl, 1 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to polycyclic dihydrothiazole and to their physiologically acceptable salts and physiologically functional derivatives. Invention describes compounds of the formula (I): wherein R1 and R1' mean independently of one another atoms of hydrogen (H), fluorine (F), chlorine (Cl), bromine (Br) and iodine (J); R2 and R3 mean hydrogen atom (H); R4 means (CH2)n-R5 wherein n can be = 0-6; R5 means phenyl that can be substituted with NH-SO2-(C1-C6)-alkyl, NH-SO2-phenyl being phenyl ring up to twice-fold can be substituted with chlorine atom (Cl), (CH2)m-SO2-NH2, (CH2)-SO2-NH-(C1-C6)-alkyl, (CH2)m-SO2-N-[(C1-C6)-alkyl]2 or (CH2)m-SO2-N-[=CH-N(CH3)2] wherein m can be = 0-6, and a method for their preparing. Compounds are useful, for example, as anorexic agents used in prophylaxis or treatment of obesity.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

5 cl, 12 tbl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to substituted 8,8a-dihydro-3aH-indeno[1,2-d]thiazoles and to their physiologically acceptable salts and physiologically functional derivatives also. Invention describes compounds of the formula (I): wherein R1 and R1' mean independently of one another H, F, Cl, Br, J; R2 and R3 means H; R4 means phenyl hat can be replaced with hydroxyl group (OH); R5 means hydrogen atom (H); R6 means OH. Also, invention describes a method for preparing these compounds. Compounds can be used as anorexic agents for prophylaxis and treatment of obesity.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

5 cl, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula II as neuropeptide FF receptor antagonist, their pharmaceutically acceptable acid-additive salts, medication based on them, as well as their application. Compounds can be applied for treatment and prevention of diseases mediated by activity of neuropeptide FF receptor, such as pain, hyperalgesia, enuresis, for elimination of syndromes arising in case of alcohol, psychotropic and nicotine addiction, for regulation of insulin release, digestion, memory functions, blood pressure or electrolytic and energy exchange. In general formula II , A together with thiazole ring forms 4,5,6,7-tetrahydrobenzothiazole, 5,6,7,8-tetrahydro-4H-cycloheptathiazole, 5,6-dihydro-4H-cyclopentathiazole fragments; R1 represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tret-butyl, 1,1-dimethylpropyl or phenyl; R2-R6 each represents hydrogen or methyl.

EFFECT: obtaining solutions, which ca be used for treatment and prevention of diseases, mediated by activity of neuropeptide FF receptor.

6 cl, 4 tbl, 106 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-acyl-2-aminothiazoles of formula (I) and their pharmaceutically acceptable salts as antagonist of adenosine receptor A2B and to a pharmaceutical composition based on the said compounds. In formula (I) X is -CH2-, -CH2CH2-, -(CH2)3- and O(CH2)-; R is a 5- or 6-member saturated or unsaturated carbocyclic or heterocyclic ring system, which can optionally contain one or more heteroatoms, chosen from N, O and S, where the said ring system is optionally substituted with one or more substitutes, chosen from a group consisting of halogen, hydroxy, lower alkyl, nitrile group, sulfonamide, aminosulfonyl, lower alkoxycarbonyl, lower alkylsufonyl, benzyl, benzoyl, phenylsulfonyl, and the said benzyl, benzoyl or phenylsulfonyl are optionally substituted with a halogen, trihalogeno-lower alkyl group; R1 is chosen from a group consisting of hydrogen, halogen or lower alkoxy group.

EFFECT: obtaining compounds which can be used for treating and preventing diseases caused by adenosine receptors A2B, such as diabetes, diabetic retinopathy, asthma and diarrhea.

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to 5-member azacyclic compounds of formula

,

where X denotes S; Y denotes O; Q denotes O; R1 denotes methyl or, together with R2, forms a 6-member aliphatic ring, R2 denotes methyl or, together with R1, forms a 6-member aliphatic ring; R3 denotes hydrogen; R4 denotes benzyl; Z- is a pharmaceutically acceptable acid radical. The invention also relates to a pharmaceutical composition, use of formula (I) compounds, which are active in destruction of advanced glycosylation end products (AGE), to obtain a medicinal agent and a method producing formula (I) compounds.

EFFECT: obtaining compounds of formula (I) which are active in destruction of advanced glycosylation end products (AGE).

6 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where R denotes a substituted or unsubstituted thiazolyl group of formula or ; R4 and R5, each independently, are selected from i) hydrogen; ii) a substituted or unsubstituted C1-C6 linear, C3-C6 branched or C3-C6 cyclic alkyl; iii) a substituted or unsubstituted phenyl; iv) a substituted or unsubstituted heteroaryl containing 5 or 6 ring atoms and 1 or 2 heteratoms, where the heteroatoms are selected from nitrogen, oxygen, sulphur and combination thereof; or R4 and R5 can be taken together to form a saturated or unsaturated ring, having 5-7 atoms; said substitutes are independently selected from one or more groups, selected from C1-C6 linear, C3-C6 branched or C3-C6 cyclic alkyl, halogen, hydroxyl or cyano; R6 denotes a group selected from i) hydrogen; ii) a substituted or unsubstituted C1-C6 linear, C3-C6 branched or C3-C6 cyclic alkyl; iii) a substituted or unsubstituted phenyl or iv) a substituted or unsubstituted heteroaryl containing 5 or 6 ring atoms and 1 or 2 heteroatoms, where the heteroatoms are selected from nitrogen, oxygen, sulphur and combination thereof; where said substitutes are independently selected from one or more groups selected from C1-C6 linear, C3-C6 branched or C3-C6 cyclic alkyl, halogen, hydroxyl or cyano; R1 is selected from i) hydrogen; ii) C1-C6 linear or C3-C6 branched alkyl; iii) a substituted or unsubstituted phenyl or iv) a substituted or unsubstituted benzyl; where said substitutes are independently selected from one or more groups selected from C1-C6 linear, C3-C6 branched or C3-C6 cyclic alkyl, halogen, hydroxyl or cyano; R2 is selected from i) C1-C6 linear or C3-C6 branched alkyl or ii) C1-C6 linear or C3-C6 branched alkoxy; R3 denotes hydrogen or C1-C4 linear or C3-C6 branched alkyl.

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

20 cl, 10 tbl, 8 ex

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