4-substituted imidazole-2-thiones and imidazole-2-ones as agonists of alpha2b- and alpha2c-adrenergic receptors

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

 

The text descriptions are given in facsimile form.

1. The compounds of formula

where the variable Y in the ring is optional and represents a heteroatom selected from N, O and S, provided that at the m N is trivalent, and the atoms On or S - ferrous;

k is an integer from 0 to 1;

n is an integer of 0, 1 or 2;

p is an integer of 0, 1 or 2;

X is O or S;

dotted lines represent communication or lack thereof, provided that the ring has only one double bond, and two adjacent dotted lines of communication are not;

R1, R2, R3and R4independently represent H, phenyl, where the specified phenyl group optionally independently substituted by one, two or three substituents - C1-6-alkyl, SO3N, N3, halogen, CN, NO2, NH2C1-6-alkoxy, C1-6-dialkoxy, C1-6-alkylaminocarbonyl, C1-6-dialkylamino,2-6-quinil,2-6-alkenyl; 5 - or 6-membered heteroaryl containing from 1 to 3 heteroatoms selected from O, S and N, where mentioned heteroaryl groups are optionally independently substituted by one, two or three substituents - C1-6-alkyl, SO3N, N3, halogen, CN, NO2, NH2With1-6-alkoxy, C1-6-dialkoxy, C1-6-alkylaminocarbonyl,1-6-dialkylamino,2-6-quinil,2-6-alkenyl,

or the groups of R1, R2, R3and R4independently represent an alkyl containing from 1 to 4 atoms ogder is Yes, cycloalkyl containing from 3 to 5 carbon atoms, CH2CN, CH2SR5CH2NR6R6, COR5CH2OR5OR6, SR6, NR6R6alkenyl containing from 1 to 4 carbon atoms, quinil containing from 1 to 4 carbon atoms, cycloalkyl containing from 3 to 6 carbon atoms, fluorine, chlorine, bromine, iodine, CF3or CN, oxygen atom, connected by a double bond with the carbon ring, provided that adjacent dotted line inside the ring means no communication;

R5means N, OR7, alkyl containing from 1 to 4 carbon atoms, CF3cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3or R5represents 5 - or 6-membered heteroaryl containing from 1 to 3 heteroatoms selected from O, S and N, and 5 - or 6-membered heteroaryl containing from 1 to 3 heteroatoms selected from O, S and N, substituted with one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3;

R6means H, alkyl containing from 1 to 4 carbon atoms, allyl, cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 at the MOU carbon fluorine, chlorine, bromine, iodine or CF3or R6represents 5 - or 6-membered heteroaryl containing from 1 to 3 heteroatoms selected from O, S and N, or a 5 - or 6-membered heteroaryl containing from 1 to 3 heteroatoms selected from O, S and N, substituted with one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3;

R7means H, alkyl containing from 1 to 4 carbon atoms, allyl, cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3;

R1and R2or R2and R3or R3and R4together may form a ring with the respective carbon atoms to which they are attached; fragments represented by the substituents R1and R2or R2and R3or R3and R4have formula (i), (ii), (iii), (iv) or (v)

where m is an integer from 0 to 3;

R8independently represents H, alkyl containing from 1 to 6 carbon atoms, alkenyl containing from 2 to atomov carbon quinil containing from 2 to 6 carbon atoms, SO3N, N3, CN, NO2, F, Cl, Br, I, CF3, COR9CH2OR9OR10; SR10C1-6-alkylamino or C1-6-dialkylamino,

R9means H, alkyl containing from 1 to 6 carbon atoms, or or10and

R10independently represents H or alkyl containing from 1 to 6 carbon atoms,

moreover, if the compound is 2-(2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl)-3,4-dihydro-2H-naphthalen-1-one, it is a (-)S or (+)R isomer.

2. The compound according to claim 1, where R is equal to the unit.

3. The compound according to claim 1, where R is equal to zero.

4. The compound according to claim 1, where [C(R10)]pmeans of CH2.

5. The compound according to claim 1, where n is equal to zero.

6. The compound according to claim 1, where n is the unit.

7. The compound according to claim 1, where n is equal to two.

8. The compound according to claim 1, where R1, R2, R3and R4independently represent hydrogen, alkyl containing from 1 to 4 carbon atoms, oxoprop, ethinyl, CH2CN, Cl, Br or cyclopropyl.

9. The compound according to claim 1, where R1and R2or R2and R3or R3and R4form a 5 - or 6-membered carbon ring, which is aromatic, saturated or partially unsaturated.

10. The connection according to claim 9, where R8independently represents H, alkyl, soda is containing from 1 to 4 carbon atoms, OR9, Cl, Br, I, F or CH2OH.

11. The compound according to claim 1, where the group R1and R2or R2and R3or R3and R4form a heteroaromatic ring selected from the group consisting of pyridyl, teinila, furil, pyrrolyl and imidazolyl.

12. Connection claim 11, where the heteroaromatic ring as heteroatom contains one atom N.

13. The compound according to claim 1, where Y represents S or O.

14. The compound according to claim 1, where one of the groups R1, R2, R3or R4is phenyl or phenyl independently substituted by one, two or three groups With1-6-alkyl, SO3N, N3, halogen, CN, NO2, NH2With1-6-alkoxy, C1-6-dialkoxy, C1-6-alkylaminocarbonyl, C1-6-dialkylamino,2-6-quinil or2-6-alkenyl.

15. The connection 14, where the phenyl group substituted by one or two substituents - alkyl, CN, NO2, F, or alkoxy.

16. The compound according to claim 1, where one of the groups R1, R2, R3or R4is heteroaryl or heteroaryl, independently substituted one, two or three substituents - C1-6-alkyl, SO3N, N3, halogen, CN, NO2, NH2C1-6-alkoxy, C1-6-dialkoxy, C1-6-alkylaminocarbonyl, C1-6-dialkylamino,2-6-quinil,2-6-Ala is the Nile.

17. Connection P16, where the heteroaryl group is thienyl or chlorine substituted thienyl.

18. The compound according to claim 1, where X is S.

19. The compound according to claim 1, where X is SO.

20. The compound of the formula

where X is O or S;

dotted lines represent communication or lack thereof, provided that the ring has only one double bond, and two adjacent dotted lines of communication are not;

R1, R2, R3and R4independently represent H, phenyl, which may be independently substituted one, two or three substituents - C1-6-alkyl, SO3N, N3, halogen, CN, NO2, NH2C1-6-alkoxy, C1-6-dialkoxy, C1-6-alkylaminocarbonyl, C1-6-dialkylamino,2-6-quinil,2-6-alkenyl; or

these groups of R1, R2, R3and R4independently represent an alkyl containing from 1 to 4 atoms of ordered, cycloalkyl containing from 3 to 5 carbon atoms, CH2CN, CH2SR5CH2NR6R6, COR5CH2OR5OR6, SR6, NR6R6alkenyl containing from 1 to 4 carbon atoms, quinil containing from 1 to 4 carbon atoms, cycloalkyl containing from 3 to 6 carbon atoms, F, Cl, Br, I, CF 3or CN, oxygen atom, connected by a double bond with the carbon ring, provided that adjacent dotted line inside the ring means no communication;

R5means N, OR7, alkyl containing from 1 to 4 carbon atoms, CF3cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3;

R6means H, alkyl containing from 1 to 4 carbon atoms, allyl, cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3and

R7means H, alkyl containing from 1 to 4 carbon atoms, allyl, cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3.

21. Connection claim 20, where X is S.

22. The compound of the formula

where X is O or S;

dotted lines represent communication or lack thereof, provided that the ring has only one double bond, and two adjacent dotted lines of communication are not;

R1, R2, R3and R4independently represent H, phenyl, which may be independently substituted one, two or three substituents - C1-6-alkyl, SO3N, N3, halogen, CN, NO2, NH2With1-6-alkoxy, C1-6-dialkoxy,1-6-alkylaminocarbonyl,1-6-dialkylamino,2-6-quinil,2-6-alkenyl; or

these groups of R1, R2, R3and R4independently represent an alkyl containing from 1 to 4 atoms of ordered, cycloalkyl containing from 3 to 5 carbon atoms, CH2CN, CH2SR5CH2NR6R6, COR5CH2OR5OR6, SR6, NR6R6alkenyl containing from 1 to 4 carbon atoms, quinil containing from 1 to 4 carbon atoms, cycloalkyl containing from 3 to 6 carbon atoms, F, Cl, Br, I, CF3or CN, oxygen atom, connected by a double bond with the carbon ring, provided that adjacent dotted line inside the ring means no communication;

R5means N, OR7, alkyl containing from 1 to 4 carbon atoms, CF3cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3;

R6means N, Ala is l, containing from 1 to 4 carbon atoms, allyl, cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3and

R7means H, alkyl containing from 1 to 4 carbon atoms, allyl, cycloalkyl containing from 3 to 6 carbon atoms, phenyl, phenyl substituted by one or two alkyl groups containing from 1 to 4 carbon atoms, fluorine, chlorine, bromine, iodine or CF3.

23. Connection p.22, where X is S.

24. Connection item 23, having the formula

25. Activation of alpha2Bor alpha2C-adrenergic receptors in mammals in need of such activation comprising the administration to a mammal a pharmaceutical composition containing a therapeutically effective dose of a compound according to claim 1.

26. The method according A.25 where the pharmaceutical composition is administered to a mammal for pain relief.

27. The method according A.25 where the pharmaceutical composition is administered to a mammal to alleviate chronic pain.

28. The method according A.25 where the pharmaceutical composition is administered to a mammal to facilitate allodynia.

29. The method according A.25 where the pharmaceutical composition is administered orally.

30. The method according A.25, where the pharmaceutical is Yu composition is administered intraperitoneally.

31. The method according A.25, where the mammal is administered the composition for treating a condition selected from the group consisting of chronic pain, visceral pain, neuropathic pain, corneal pain, glaucoma, elevated intraocular pressure, ischemic neuropathies, neurodegenerative diseases, diarrhea, nasal congestion, muscle spasticity, diuresis, withdrawal syndromes, neurodegenerative diseases, optic neuropathy, spinal ischemia, stroke, memory deficit, cognitive deficit, attention deficit, psychoses, manic disorders, anxiety, depression, hypertension, congestive heart failure, cardiac ischemia, arthritis, spondylitis, gouty arthritis, osteoarthritis, juvenile arthritis, autoimmune diseases, lupus erythematosus, chronic gastrointestinal inflammations, diseases of the Crown, gastritis, irritable bowel syndrome, functional dyspepsia and ulcerative colitis.

32. The method according to p, where the mammal is administered the composition for treating glaucoma.

33. The method according to p, where the mammal is administered the composition for treating neuropathies or neurodegenerative diseases.

34. The method according to p, where the mammal is administered the composition for treating muscle spasticity.



 

Same patents:

The invention relates to new derivatives of tamilcanadian with the General formula (I) wherein R' represents 2-thienyl or 3-thienyl radical, R represents ceanorhaditis or a radical of the formula-C(O) - and R2 is optional saturated or unsaturated cyclic hydrocarbon radical or aryl radical

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to phthalimido-derivatives of the general formula (I): wherein X means -N= or -CH=; R1 means -CO-NR5R6, -CHR7-(CH2)n-CO-NR5R6, -(CH2)n-NR5R6, -(CH2)n-COOR8, -(CH2)n-CN, -CHR7-(CH2)n-CF3, -(CH2)n-NH-COR9, -(CH2)n-NH-COOR8, -(CH2)n-piperidinyl, -(CH2)n-morpholinyl, -(CH2)n-tetrahydrofuranyl, -(CH2)n-thiophenyl or -(CH2)n-isoxazolyl wherein a heterocyclic ring can be substituted with (C1-C6)-alkyl; -(CH2)n-phenyl wherein phenyl ring can be substituted with halogen atom or halogen-(C1-C6)-alkyl; -(CH2)p-OR8, -(CH2)p-SR8, -(CH2)p-SO-R9 or -(CH2)n-CS-NR5R6; R2 means hydrogen atom (H), (C1-C6)-alkyl, -(CH2)p-OR10, -(CH2)p-SR or benzyl; R3 means H, (C1-C6)-alkyl; R4 means halogen atom, halogen-(C1-C6)-alkyl, cyano-, (C1-C6)-alkoxy- or halogen-(C1-C6)-alkoxy-group; Each R5 and R6 means independently of one another H, (C1-C6)-alkyl; R7 means H, -OH, (C1-C6)-alkoxy-group; R8 means H, (C1-C6)-alkyl; R9 means (C1-C6)-alkyl; R10 means H, (C1-C6)-alkyl; m = 1, 2 or 3; n = 0, 1 or 2; p = 1 or 2, and their pharmaceutically acceptable salts. Compounds of the formula (I) inhibit activity of monoamine oxidase B (MAO B) that allows their using as a drug.

EFFECT: valuable medicinal and biochemical properties of compounds.

14 cl, 4 sch, 1 tbl, 53 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with describing the efficient quantity of, at least, one heterocyclic compound of formula (I) or its salts, moreover, the compound of formula (I) should be chosen out of (i) the compounds of formula (III) or their salts, in which Z, Z' indicate O, X indicates S (thiazolidine dionic group), G indicates O or S; at least, one out of R2 and R3 indicates CF3, OR0 or COOR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C10-C10-alkyl, (ii) compounds (VI) or their salts: in which Z, Z' and G independently indicate O or S, at least, one out of R2 and R3 indicates hydrogen, CN, CF3, NO2, OR0, COOR0 or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, possibly substituted OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, (iii) compounds (VII) or their salts in which Z, Z' and G independently indicate O or S; R indicates saturated linear or branched C1-C10-alkyl; at least, one out of R2 and R3 indicates saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, NO2, OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl. The compounds in question reveal improved action upon stimulation of keratin fibers growth, particularly, human keratin fibers, that prevents their falling down and increases their density.

EFFECT: higher efficiency.

31 cl, 13 ex, 6 tbl

FIELD: medicine, pharmacology.

SUBSTANCE: invention relates to new enantiomerically pure (-)3-((S)-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-thienyl)methyl)phenol, pharmaceutical composition containing the same having antagonistic activity in relates to μ- and/or δ-opioid receptors; methods for treatment of pain, cough, functional diarrhea, functional pain, heart diseases, emesis; method for receptor-mediated analgesia; method for amelioration, treatment and prevention of drug-mediated respiratory depression; method for screening of compounds suppressing opioid respiratory depression; pharmaceutical composition containing biologically active agent for treatment of pain, cough, functional diarrhea, functional pain, heart diseases, emesis, respiratory depression and claimed compound; and method for performance of reaction mediated with opioid receptors.

EFFECT: therapy of increased effectiveness.

17 cl, 6 dwg, 4 tbl, 7 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: Described are derivatives of general formula I (all symbols are as described in specification), pharmaceutically acceptable salts thereof or cyclodextrin clathrates. Such compounds hardly bind of EP2 subtype of PGE receptor and are useful in prophylaxis of immune diseases, allergy, death of neuronal cells, liver or kidney insufficiency, etc.

EFFECT: new agent for prophylaxis of various diseases.

18 cl, 388 ex, 68 tbl, 3 dwg

FIELD: organic chemistry.

SUBSTANCE: invention relates to new pyrasole derivatives of formula I wherein R5 represents phenyl or heteroaryl ring of formulae IIIa-IIIh meanings of the rest substituents are as defined in specification. Also disclosed are pharmaceutical composition based on said derivatives of formula I and uses thereof.

EFFECT: new biologically active compounds and pharmaceutical compositions based on the same for HIV inhibition.

13 cl, 54 ex, 2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to 1-[1-(hetero)aryl-1-perhydroxyalkylmethyl]piperazine compounds of the general formula (I): wherein A means naphthyl, phenyl optionally substituted with methoxy-group, heteroaryl chosen from group comprising thienyl, furyl, indolyl or (C3-C6)-alkenyl optionally substituted with phenyl; Z means subgroup of the general formula: wherein k, l, m and n mean 0 or 1; R6 and R7 mean halogen atom, and to their physiologically acceptable acid-additive salt. Compounds possess antagonistic activity with respect to tachykinin receptors and can be used in treatment of digestive tract functional and inflammatory disorders. Also, invention describes a method for synthesis of proposed compounds and intermediate substances used in realization of this method, and medicinal agents containing indicated compounds.

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

9 cl, 3 tbl, 40 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel compounds of the general formula (I) wherein p, R1, R2, R3 and A are determined in the invention description, their individual isomers and their pharmaceutically acceptable salts. Proposed compounds possess antagonistic effect with respect to muscarinic receptors that allows their using in treatment and prophylaxis of diseases yielding to treatment with muscarinic receptor antagonist. Also, invention describes a pharmaceutical composition containing these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 22 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to a new biologically active compound of 4-oxoquinoline that is useful as an anti-HIV agent and to its pharmaceutically acceptable salt. Invention describes an anti-HIV agent comprising compound of 4-oxoquinoline represented by the following formula [I] or its pharmaceutically acceptable salt as an active component wherein ring Cy represents phenyl group, naphthyl group or pyridyl group and each this group is substituted optionally with 1-5 substituted chosen from the following group A wherein A represents the group consisting of cyano-group, phenyl group, nitro-group, halogen atom, (C1-C4)-alkyl group, halogen-(C1-C4)-alkyl group, halogen-(C1-C4)-alkoxy-group, -ORa1, -SRa1, -NRa1Ra2, -CONRa1Ra2, -SO2NRa1Ra2, -NRa1CORa3, -SO2Ra3, -NRa1SO2Ra3 and -COORa1 wherein Ra1 and Ra2 are similar or different and each represents hydrogen atom, (C1-C4)-alkyl group or benzyl group, and Ra3 represents (C1-C4)-alkyl group; R1 represent a substitute chosen from the following group B, or (C1-C10)-alkyl group optionally substituted with 1-3 substitutes chosen from halogen atom and the following group B wherein the group B represents the group consisting of phenyl group optionally substituted with phenyl group or 1-5 halogen atoms; (C3-C6)-cycloalkyl group, imidazolyl group, benzothiophenyl group, thiazolyl group optionally substituted with 1-3 (C1-C6)-alkyl groups, morpholinyl group, pyridyl group, -ORa4, -SRa4, -NRa4Ra5, -CONRa4Ra5, -SO2NRa4Ra5, -CORa6, -NRa4CORa6, -SO2Ra6, -NRa4SO2Ra6, -COORa4 and -NRa5COORa6 wherein Ra4 and Ra5 are similar or different and each represents hydrogen atom, (C1-C4)-alkyl group or phenyl group; Ra6 represents (C1-C4)-alkyl group; R2 represents hydrogen atom or (C1-C4)-alkyl group; R31 represents hydrogen atom, cyano-group, hydroxy-group, halogen atom or (C1-C4)-alkoxy-group; X represents -C-R32, and Y represents -C-R33 or nitrogen atom wherein R32 and R33 are similar or different and each represents hydrogen atom, cyano-group, halogen atom, pyrrolidinyl group, (C1-C10)-alkyl group optionally substituted with 1-3 halogen atoms, -ORa7, -SRa7, -NRa7Ra8, -NRa7CORa9, -COORa10 or -N=CH-NRa10Ra11 wherein Ra7 and Ra8 are similar or different and each represents hydrogen atom, phenyl group or (C1-C10)-alkyl group optionally substituted with (C3-C6)-cycloalkyl group or hydroxy-group; Ra9 represents (C1-C4)-alkyl group and Ra10 and Ra11 are similar or different and each represents hydrogen atom or (C1-C4)-alkyl group. Also, invention describes compound of the formula (III) given in the invention description, integrase inhibitor, antiviral agent, ant-HIV composition, anti-HIV agent, using compound of 4-oxoqionoline, method for inhibition of integrase activity, method for prophylaxis or treatment of viral infectious disease, pharmaceutical composition used for inhibition of integrase activity, antiviral composition and commercial package (variants). Invention provides the development of a pharmaceutical agent possessing inhibitory effect on activity of integrase.

EFFECT: valuable medicinal properties of compound, agent and composition.

40 cl, 7 tbl, 250 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes derivative of 3,4-dihydroisoquinoline of the formula (I) or its nontoxic salt and a pharmaceutical agent comprising its as an active component (wherein all symbols have the same values as given in description). Compound of the formula (I) possesses agonistic effect on CB2-receptors and, therefore, it can be used for prophylaxis and/or treatment of different diseases, for example, asthma, nasal allergy, atopic dermatitis, autoimmune diseases, rheumatic arthritis, immune dysfunction, postoperative pain and carcinomatous pain.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 33 tbl, 561 ex

Muscarinic agonists // 2269523

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein Z1 represents -CR1 or nitrogen atom (N); Z2 represents -CR2; Z3 represents -CR3 or N; Z4 represents -CR4; W1 represents oxygen (O), sulfur (S) atom or -NR5; one of W2 and W3 represents N or -CR6 and another among W2 and W3 represents CG; W1 represents NG; W2 represents -CR5 or N; W3 represents -CR6 or N; or W1 and W3 represent N and W2 represents NG; G represents compound of the formula (II): wherein Y represents oxygen atom (O), -C(O)- or absent; p = 1, 2, 3, 4 or 5; Z is absent; each t = 2. Also, invention describes a method for enhancing activity of the muscarinic cholinergic receptor and a method for treatment of morbid states when modification of cholinergic and, especially, muscarinic receptors m1, m4 or both m1 and m4 offers the favorable effect.

EFFECT: valuable medicinal properties of agonists.

14 cl, 2 tbl, 101 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to phthalimido-derivatives of the general formula (I): wherein X means -N= or -CH=; R1 means -CO-NR5R6, -CHR7-(CH2)n-CO-NR5R6, -(CH2)n-NR5R6, -(CH2)n-COOR8, -(CH2)n-CN, -CHR7-(CH2)n-CF3, -(CH2)n-NH-COR9, -(CH2)n-NH-COOR8, -(CH2)n-piperidinyl, -(CH2)n-morpholinyl, -(CH2)n-tetrahydrofuranyl, -(CH2)n-thiophenyl or -(CH2)n-isoxazolyl wherein a heterocyclic ring can be substituted with (C1-C6)-alkyl; -(CH2)n-phenyl wherein phenyl ring can be substituted with halogen atom or halogen-(C1-C6)-alkyl; -(CH2)p-OR8, -(CH2)p-SR8, -(CH2)p-SO-R9 or -(CH2)n-CS-NR5R6; R2 means hydrogen atom (H), (C1-C6)-alkyl, -(CH2)p-OR10, -(CH2)p-SR or benzyl; R3 means H, (C1-C6)-alkyl; R4 means halogen atom, halogen-(C1-C6)-alkyl, cyano-, (C1-C6)-alkoxy- or halogen-(C1-C6)-alkoxy-group; Each R5 and R6 means independently of one another H, (C1-C6)-alkyl; R7 means H, -OH, (C1-C6)-alkoxy-group; R8 means H, (C1-C6)-alkyl; R9 means (C1-C6)-alkyl; R10 means H, (C1-C6)-alkyl; m = 1, 2 or 3; n = 0, 1 or 2; p = 1 or 2, and their pharmaceutically acceptable salts. Compounds of the formula (I) inhibit activity of monoamine oxidase B (MAO B) that allows their using as a drug.

EFFECT: valuable medicinal and biochemical properties of compounds.

14 cl, 4 sch, 1 tbl, 53 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with describing the efficient quantity of, at least, one heterocyclic compound of formula (I) or its salts, moreover, the compound of formula (I) should be chosen out of (i) the compounds of formula (III) or their salts, in which Z, Z' indicate O, X indicates S (thiazolidine dionic group), G indicates O or S; at least, one out of R2 and R3 indicates CF3, OR0 or COOR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C10-C10-alkyl, (ii) compounds (VI) or their salts: in which Z, Z' and G independently indicate O or S, at least, one out of R2 and R3 indicates hydrogen, CN, CF3, NO2, OR0, COOR0 or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, possibly substituted OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, (iii) compounds (VII) or their salts in which Z, Z' and G independently indicate O or S; R indicates saturated linear or branched C1-C10-alkyl; at least, one out of R2 and R3 indicates saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl, NO2, OR0, where R0 indicates H or saturated linear or branched C1-C20-alkyl and, preferably, C1-C10-alkyl. The compounds in question reveal improved action upon stimulation of keratin fibers growth, particularly, human keratin fibers, that prevents their falling down and increases their density.

EFFECT: higher efficiency.

31 cl, 13 ex, 6 tbl

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes derivatives of aminotetraline of the formula (I) wherein R1 means (C1-C6)-alkyl; R2 means halogen atom or -OR'; R3 means hydrogen atom (H) or -OR' wherein R' means (C1-C6)-alkyl or -SO2R'' wherein R'' means phenyl, thienyl, isoxazolyl; R4 means (C1-C6)-alkyl, phenyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, diazepinyl, furanyl, isoxazolyl, imidazolyl and pyrazolyl that can be substituted optionally, and pharmaceutical compositions containing derivatives of aminotetraline. Proposed compounds are selective antagonists of M2/M3 muscarinic receptors and designated for treatment and prophylaxis of diseases associated with smooth muscle disorder.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 1 tbl, 16 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new benzopyran-4-ones of formula , wherein R1 is benzyl, chlorobenzyl, methylbanzyl, methoxybenzyl, cyanobenzyl, etc.; R2 and R2' are independently hydrogen, C1-C4-alkyl; substituted C1-C4-alkyl; R12 is -N(R4)(CO R3); R3 is phenyl optionally substituted with C1-C4-alkyl; R4 is C1-C4-alkyl optionally substituted with amino group; R5, R6, and R7 are hydrogen; R7 is hydrogen, halogen, hydroxy, C1-C4-alkoxy, and cyano; as well as specific stereoisomers thereof and stereoisomer mixtures. Also disclosed is pharmaceutical composition based on said compounds, method for modulation of KSP kynezine activity and using of said compounds in production of drugs for treatment of cell proliferative diseases.

EFFECT: new compound with pharmaceutical activity.

19 cl, 3 dwg, 4 tbl, 26 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to alkylated (1H-benzimidazol-5-yl)-(-4-substituted phenyl)-amine derivatives, in particular compound of formula and pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, and R9, are independently hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluorimethoxy, azido, etc.; R7 is optionally substituted C1-C10-alkyl, C3-C10-cycloalkyl, etc.; A is-OR3 or NR4R3; R8 is hydrogen, -Cl, -Br, -F, cyano, nitro, etc.; and meanings of the rest substituents are as defined in specification. Also disclosed is composition for MEK inhibition and uses of benzinidazole compounds.

EFFECT: new compounds with value biological properties.

32 cl, 56 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): wherein R means -C(O)R1 wherein R1 is chosen from the series: (C1-C6)-alkyl, -C=CH-COOH, -NHCH2-CH2R2, -N(CH2-CH2OH)CH2-CH2OH, -N(CH3)CH2-CH2-NHCH3, -N(CH3)CH2-CH2N(CH3)CH3, saturated 4-, 5- and 6-membered cycles and saturated and unsaturated 5- and 5-membered cycles comprising at least one heteroatom from a series sulfur (S), nitrogen (N) and oxygen (O), and optionally substituted with a group chosen from the series: (C1-C6)-alkyl, -C=O-R5, -OH, (C1-C6)-alkyl substituted with hydroxy-group optionally, (C1-C6)-alkyl substituted optionally with a group of the series: -NH2, -N-(C1-C6)-alkyl, -SO2CH3, =O, and 5- and 6-membered saturated cycles comprising at least one heteroatom chosen from N and O, and wherein R5 is chosen from the series: hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-alkyl substituted with hydroxy-group optionally, and (C1-C6)-alkyl substituted with NH2-group optionally; R2 is chosen from the series: -N(CH3)CH3, -NH2, morpholinyl and piperazinyl; X1, X2 and X3 are chosen independently from the series: -OH, (C1-C2)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CH2OCH3 and -CH2OCH2CH3, or one among X1, X2 or X3 means hydrogen atom, and two others are chosen independently from the series: hydroxy-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CF3, -CH2OCH3, -CH2OCH2CH3, -OCH2-CH2R3, -OCH2-CF3 and -OR4, morpholylmethyl, -N(CH3)CH3, -CH2OH, -COOH, or one among X1, X2 or X3 means hydrogen atom, and two others in common with two carbon atoms including bonds between them in benzene cycle to which they are bound optionally form 5- or 6-membered saturated cycle comprising at least one heteroatom chosen from S, N and O, and wherein R3 is chosen from the series: -F, -OCH3, -N(CH3)CH3, saturated 5-membered cycle comprising at least one heteroatom N; R4 means 3-5-membered saturated cycle, and each Y1 and Y2 is chosen independently from the series: -Cl, -Br, -NO2,-C≡N and C≡N, and compound of the formula (II) also given in the invention description. Also, invention relates to a pharmaceutical composition possessing anti-proliferative activity and based on these compounds. Invention provides preparing novel compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 39 ex

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, pharmacy.

SUBSTANCE: invention describes novel compounds of the general formula (I) wherein p, R1, R2, R3 and A are determined in the invention description, their individual isomers and their pharmaceutically acceptable salts. Proposed compounds possess antagonistic effect with respect to muscarinic receptors that allows their using in treatment and prophylaxis of diseases yielding to treatment with muscarinic receptor antagonist. Also, invention describes a pharmaceutical composition containing these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 22 ex

FIELD: organic chemistry, medicine, biochemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of pure enantiomers of inhibitors of HMG-CoA-reductase. Invention describes a method for synthesis of compound of the formula (I): or its salt, especially pharmaceutically acceptable salt with a base, or its lactone wherein a member represents -CH2-CH2- or -CH=CH-, and R represents a cyclic residue. Invention provides the enantioselective synthesis of compounds of the formula (I) with high yields, decreasing ecological pollution of environment and possibility for carrying out the large-scale manufacturing.

EFFECT: improved method of synthesis.

6 cl, 1 ex

FIELD: organic chemistry, chemical technology, biochemistry, medicine.

SUBSTANCE: invention relates to novel isoquinoline compounds of the general formula (I): wherein R1 represents hydrogen atom, halogen atom or alkyl; Y is absent or represents alkylene chain comprising from 1 to 8 carbon atoms wherein arbitrary carbon atom can comprise hydroxyl group as a substitute; R represents the following formula (II): wherein X represents -CH or nitrogen atom under condition that if Y absent in the formula (I) then X must represent -CH; W represents -CH or nitrogen atom under condition that if X represents -CH then W must represents nitrogen atom; s represents a whole number from 1 to 3; t represents a whole number from 1 to 3; if R3 represents hydrogen atom or alkyl then R2 represents hydrogen atom, alkyl, hydroxyl group or hydroxyalkyl, and R2' represents hydroxyl group or hydroxyalkyl, and if R3 represents hydroxyalkyl then R2 and R2' represent hydrogen atom. Also, invention relates to their optically active forms, pharmaceutically acceptable salts, aqueous adducts, hydrates and solvates. Compounds of the formula (I) elicit inhibitory effect on activity of poly-(ADP-ribose)-polymerase and can be used in prophylaxis of diseases associated with cerebral infarction.

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

40 cl, 4 tbl, 55 ex

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