Nitrogen-containing aromatic derivatives, their using, medicinal agent based on thereof and method for treatment

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:

wherein Ag represents (1) group of the formula:

; (2) group represented by the formula:

or ; (3) group represented by the formula:

; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:

; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.

EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.

40 cl, 51 tbl, 741 ex

 

Description of the invention presented in the graphical part.

1. The connection represented by the following General formula:

where Agrepresents (1) a group represented by the formula

where W represents a carbon atom; Ra13represents a hydrogen atom; Ra12represents cyano or a group represented by the formula:

where Va11represents-CO - or-SO2-; each Va12, Va13and Va14independently represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom or an oxygen atom, or optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom or a sulfur atom; Ra11represents a group of formula-Va21-Va22-Va23where Va21represents optionally substituted C1-6alkylenes group, a simple link or a group represented by the formula:

V822represents a simple bond, oxygen atom, sulfur atom, -CO-, -SO2-, -CONRa14-, -SO2NRa14-, -NRa14SO2- or-NRa14-where Ra14represents a hydrogen atom, optionally substituted C1-6alkyl group or optionally substituted C3-8alicyclic hydrocarbon group; Va23represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom or an oxygen atom or optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom, (2) a group represented by the formula

where W represents an optionally substituted carbon atom or a nitrogen atom; andb11represents (1) an optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (2) a group represented by the formula:

where each of Vb11and Vb12independent PR is dstanley a simple link, -NHCO - or a group represented by the formula -(CH2)b-CO-, where b is an integer from 0 to 6); Rb13represents a simple bond, optionally substituted C1-6alkylenes group, optionally substituted C3-8alicyclic hydrocarbon group or optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom; each of Rb11and Rb12independently represents a hydrogen atom, halogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom, or optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (3) a group represented by the formula

where W represents a nitrogen atom; Rc13represents (1) hydrogen atom, (2) optionally substituted C1-6alkyl group or (3) a group represented by the formula:

where Vc21represents a methylene group; each of V and Vc23independently represents a hydrogen atom, optionally substituted C1-6alkyl group; Rc12represents a hydrogen atom or optionally substituted C1-6alkyl group; and Rc11represents a group of formula-Vc11-Vc12-Vc13where Vc11represents a simple bond, oxygen atom, optionally substituted benzene ring, optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom, or-CO-; Vc12represents a simple bond or an oxygen atom; Vc13represents (1) optionally substituted C1-6alkyl group, (2) hydroxyl group, (3) carboxyl group, (4) optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (5) a hydrogen atom;

X9represents-O-, -S-, C1-6alkylenes group, or-N(Rg3)-, where Rg3represents a hydrogen atom;

Ygrepresents optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom or a sulfur atom, optionally substituted C1-8alkyl group;

Tg1means (1) group is at, represented by the following General formula:

where Egrepresents a simple bond or-N(Rg2)-, where Rg2represents a hydrogen atom or optionally substituted C1-6alkyl group;

Rg1represents a hydrogen atom;

Zgrepresents a hydrogen atom, optionally substituted C1-8alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, -SO2R200where R200represents optionally substituted C1-8alkyl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as nitrogen atom, oxygen atom or sulfur atom, or

(2) a group represented by the following General formula:

where Rg1and Zghave the same meanings as Rg1and Zgdescribed above; Zg1and Zg2may be the same or different and each represents a simple bond,

its salt or hydrate.

2. The connection represented by the following General formula:

where a represents a group of the formula

where W represents a carbon atom; Ra13represents a hydrogen atom; Ra12represents cyano or a group represented by the formula:

where Va11represents-CO - or-SO2-; each Va12, Va13and Va14independently represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom or an oxygen atom, or optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom or a sulfur atom; Ra11represents a group of formula-Va21-Va22-Va23where Va21represents optionally substituted C1-6alkylenes group, a simple link or a group represented by the formula:

Va22represents a simple bond, oxygen atom, sulfur atom, -CO-SO2-, -CONRa14-, -SO2NRal4-, -NRal4SO2- or-NRa14-where Ra14represents a hydrogen atom, optionally substituted C1-6the alkyl group is at or optionally substituted C 3-8alicyclic hydrocarbon group; Va23represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom or an oxygen atom, or optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom, (2) a group represented by the formula

where W represents an optionally substituted carbon atom or a nitrogen atom; andb11represents (1) an optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (2) a group represented by the formula:

where each of Vb11and Vb12independently represents a simple bond, -NHCO - or a group represented by the formula -(CH2)b-CO-, where b is an integer from 0 to 6; Rb13represents a simple bond, optionally substituted C1-6alkylenes group, optionally substituted C3-8alicyclic hydrocarbon group which does not necessarily substituted 5 to 14-membered heterocyclic group containing, at least one heteroatom such as a nitrogen atom; each of Rb11and Rb12independently represents a hydrogen atom, halogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom, or optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (3) a group represented by the formula

where W represents a nitrogen atom; Rc13represents (1) hydrogen atom, (2) optionally substituted C1-6alkyl group or (3) a group represented by the formula:

where Vc21represents a methylene group; each of Vc22and Vc23independently represents a hydrogen atom, optionally substituted C1-6alkyl group; Rc12represents a hydrogen atom or optionally substituted C1-6alkyl group; Rc11represents a group of formula-Vc11-Vc12-Vc13where Vc11represents a simple bond, oxygen atom, neobythites is but substituted benzene ring, optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom, or-CO-; Vc12represents a simple bond or an oxygen atom; Vc13represents (1) optionally substituted C1-6alkyl group, (2) hydroxyl group, (3) carboxyl group, (4) optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (5) a hydrogen atom;

X represents an oxygen atom or a sulfur atom;

Y represents optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered aromatic heterocyclic group containing at least one heteroatom such as a nitrogen atom or a sulfur atom, or optionally substituted C1-6alkylenes group;

E represents a simple bond or-NR2-;

R1represents a hydrogen atom;

R2independently represents a hydrogen atom or optionally substituted C1-6alkyl group;

Z stands for a group represented by formula-Z11-Z12where Z11represents a simple bond, oxygen atom, sulfur atom, -CO-, -SO2or optionally substituted C1-6alkylenes group, and Z12represents a hydrogen atom, n is necessarily substituted C 1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as nitrogen atom, oxygen atom or sulfur atom, or a group represented by the formula:

where each of the Z31, Z33and Z34independently represents a methylene group, -CO-, -NH or-O-, and Z32represents a simple bond, a methylene group, -CO-, -NH or-O-,

its salt or hydrate.

3. The compound according to claim 2 its salt or hydrate, where Z represents optionally substituted cyclopropyl group, optionally substituted 2-thiazolidine group or a group represented by the formula:

where Z13represents a nitrile group, methylsulfonyl group or group-NHCOCH3.

4. The compound according to any one of claim 2 or 3, its salt or hydrate, where E stands for a group represented by the formula-NR2-where R2has the same meaning as R2defined in claim 2, and Y represents an optionally substituted phenyl group, optionally substituted pyridyloxy group or a group represented by the formula:

where each of W11and W12independently represents an optionally substituted carbon atom or nitrogen atom.

5. The compound according to any one of claim 2 or 3, its salt or hydrate, where E represents a simple bond, and Y, in addition, represents optionally substituted group represented by the formula:

where W13represents an optionally substituted carbon atom or nitrogen atom.

6. The connection represented by the following General formula:

where R1, R2and Z12have the same meanings as R1, R2and Z12defined in section 2, but Z12is not pyrazolidine group; Ya1represents a group of the formula:

where each of W31and W32independently represents a carbon atom or a nitrogen atom; each of R300and R301independently represents a hydrogen atom, halogen atom or optionally substituted C1-6alkyl group;

Ra11and Ra12have the same meanings as Ra11and Ra12defined in claim 2, with the exception of the following compounds (1) and (2):

(1) compounds where Ra12means a group represented by the formula:

where EV is th of V a112and Va113independently represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C1-6alkenylphenol group, optionally substituted C1-6alkylamino group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group or optionally substituted 5 to 14-membered aromatic heterocyclic group, R1and R2represent hydrogen atoms, and Z12represents C6-14aryl group, 6-14-membered heterocyclic group or a 6-14-membered aromatic heterocyclic group;

(2) compounds where Ra12represents a group selected from groups represented by the formulas:

where Va111represents-CO - or-SO2-;, Va114represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C1-6alkenylphenol group, optionally substituted C1-6alkylamino group, optionally substituted C3-8alicyclic hydrocarbon group, optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered, heterocy the symbolic group or optionally substituted 5 to 14-membered aromatic heterocyclic group; Va112and Va113have the same meanings as defined above,

R2represents a hydrogen atom, and Z12represents (a) C6-14aryl group, (b) 5 to 14-membered heterocyclic group, (C) 5 to 14-membered aromatic heterocyclic group, (d) C1-6alkyl group, a substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (e) C2-6alkenylphenol group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (f) C2-6alkylamino group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, or (g) C3-8alicyclic hydrocarbon group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, its salt or hydrate.

7. The connection according to claim 6, its salt or hydrate, where Ra11represents a methyl group, 2-methoxyaniline group or a group represented by the formula:

where Ra53represents a methyl group; Ra51represents a hydrogen atom or a hydroxyl group; Ra52is 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group, dimethylaminopropyl or diethylaminopropyl.

8. With the unity of claim 6 or 7, its salt or hydrate, where Z12represents methyl group, ethyl group, cyclopropyl group, 2-thiazolidine group or 4-florfenicol group.

9. The compound according to any one of p-8, its salt or hydrate, where Ya1represents a group of the formula:

where Ra61represents a hydrogen atom, methyl group, triptorelin group, a chlorine atom or a fluorine atom.

10. The compound according to any one of p-9, its salt or hydrate, where Ra12represents cyano or a group represented by formula-CONHRa62where Ra62represents a hydrogen atom, optionally substituted C1-6alkyl group, optionally substituted C3-8alicyclic hydrocarbon group or optionally substituted C1-6alkoxygroup.

11. The connection represented by the following General formula:

where Z21represents optionally substituted C1-6alkyl group or optionally substituted C3-8alicyclic hydrocarbon group; Ra120represents cyano or a group represented by the formula:

where V315represents optionally substituted C1-6alkyl group, and Va1 , Va12and Va13have the same values as Va11, Va12and Va13defined in claim 2; R300and R301have the same meanings as R300and R301defined in claim 6; Ra11has the same meaning as Ra11defined in claim 2, with the exception of compounds where Ra120represents a group selected from the group of formulas:

where Va111, Va112, va113and Va114have the same values as Va111, Va112, Va113and Va114defined in claim 6, and Vall5represents optionally substituted C1-6alkyl group, optionally substituted C1-6alkenylphenol group, optionally substituted C1-6alkylamino group, optionally substituted C3-8alicyclic hydrocarbon group, and Z21represents (a) C3-8alicyclic hydrocarbon group, (b) C1-6alkyl group, a substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (C) C2-6alkenylphenol group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, or (d) C2-6alkylamino group, substituted 5-10-membered heterocyclic group or a C5-10alicyclics the second hydrocarbon group,

its salt or hydrate.

12. The connection represented by the following General formula:

where Z22represents optionally substituted C6-14aryl group, optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom or a sulfur atom; R300and R301represent a hydrogen atom; Vd13represents a group selected from the group of formulas:

where Va12and Va13have the same values as Va12and Va13defined in claim 2; Vd11represents optionally substituted C1-6alkylenes group, and Vd12represents (1) a group of the formula-NRd11Rd12where each of Rd11and Rd12represents a hydrogen atom or optionally substituted C1-6alkyl group); or (2) optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom,

its salt or hydrate.

13. The connection represented by the following General formula:

where R1, R2and Z12have the same meanings as R1, R2and Z12defined in claim 2; W11represents a carbon atom and the and the nitrogen atom; R300has the same meaning as R300defined in claim 6; Ra11has the same meaning as R11defined in claim 2;

and Ra120has the same meaning as Ra120defined in paragraph 11, except for the following compounds (1) and (2):

(1) compounds where Ra120represents a group of formula:

where Va112and Va113have the same meanings as in Va112and Va113defined in claim 6; R1and R2represent hydrogen atoms, and Z12represents C6-14aryl group, 6-14-membered heterocyclic group or a 6-14-membered aromatic heterocyclic group;

(2) compounds where Ra120represents a group selected from the group of formulas:

where Va111, Va112, Va113and Va114have the same values as Va111, Va112, Va113and Va114defined in claim 3, and Va115has the same meaning as Va115defined in claim 11, R2represents a hydrogen atom, and Z12represents (a) C6-14aryl group, (b) 5 to 14-membered heterocyclic group, (C) 5 to 14-membered aromatic heterocyclic group, (d) C1-6alkyl group, a substituted 5-10-membered courtesans is a cyclic group, or a C 5-10alicyclic hydrocarbon group, (e) C2-6alkenylphenol group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (f) C2-6alkylamino group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, or (g) C3-8alicyclic hydrocarbon group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group,

its salt or hydrate.

14. The connection represented by the following General formula

where each of W41and W independently represents an optionally substituted carbon atom or nitrogen atom, but W41and W both are nitrogen atoms; Xy1is optionally substituted group selected from groups of the following formulas:

where Z12has the same meaning as Z12defined in claim 2; andb11has the same meaning as Andb11defined in paragraph 2

its salt or hydrate.

15. The connection represented by the following General formula:

where Rc13has the same meaning as Rc13defined in claim 2; Xy2is neobyazatelnostyu group, selected from groups of the following formulas:

where Z12, R1and R2have the same meanings as Z12, R1and R2in certain claim 2, and W11represents a carbon atom or a nitrogen atom; Rc11and Rc12have the same meanings as Rc11and Rc12defined in claim 2;

with the exception of the following compounds (1) and (2):

(1) compounds where R1and R2represent a hydrogen atom, and Z12represents (a) C6-14aryl group, (b) 5 to 14-membered heterocyclic group, (C) C1-6alkyl group, a substituted 5-10-membered aromatic heterocyclic group, a 5-10 membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (d) C2-6alkenylphenol group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (e) C2-6alkylamino group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, or (f) C3-8alicyclic hydrocarbon group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group;

(2) compounds where Xy2means a group represented by the formula:

where Z12represents (a) C6-14aryl group, (b) 5 to 14-membered heterocyclic group, (C) 5 to 14-membered aromatic heterocyclic group, (d) C1-6alkyl group, a substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (e) C2-6alkenylphenol group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, (f) C2-6alkylamino group, substituted 5-10-membered heterocyclic group or a C5-10alicyclic hydrocarbon group, or (g) C3-8alicyclic hydrocarbon group,

its salt or hydrate.

16. The compound according to claim 2 or 15, its salt or hydrate, where Rc11represents a group of the formula:

where Vf11represents a simple bond, optionally substituted C1-6alkylenes group or a group represented by the formula:

and Vf12represents (1) hydrogen atom, (2) optionally substituted 5 to 14-membered heterocyclic group containing at least one heteroatom such as a nitrogen atom, or (3) a group represented by the formula-NRf21Rf22where each of Rf21and Rf22independently represents a hydrogen atom or optional samewe the s C 1-6alkyl group.

17. The connection represented by the following General formula:

where Z12, R1and R2have the same meanings as Z12in R1and R2defined in claim 2; R300and R301have the same meanings as R300and R301defined in claim 6; and32represents a group,

where W, Ra11, Ra12and Ra13have the same meanings as W, Ra11, Ra11and Ra13defined in paragraph 2

its salt or hydrate.

18. The compound according to claim 1, or 1, its pharmacologically acceptable salt or hydrate, where the specified connection selected from the

N-(4-(6-cyano-7-(3-(4-pyridyl)propoxy)-4-chinolin)oxyphenyl)-N'-(4-methoxyphenyl)urea,

N-(4-(6-cyano-7-(2-(1,2,3-triazole-2-yl)ethoxy-4-chinolin)oxyphenyl)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(2-(1,2,3-triazole-1-yl)ethoxy)-4-chinolin)oxyphenyl)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(2-(1,2,3-triazole-2-yl)ethoxy-4-chinolin)oxyphenyl)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(2-(1,2,3-triazole-1-yl)ethoxy-4-chinolin)oxyphenyl-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(2-(methoxyethoxy)-4-chinolin)oxyphenyl)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(2-(methoxyethoxy)-4-chinolin)oxyphenyl)-N'-(1,Z is thiazol-2-yl)urea,

p num="174"> N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)oxyphenyl)-N'-(3-cyanophenyl)urea

N-(4-(6-cyano-7-(2-(methoxyethoxy)-4-chinolin)oxyphenyl)-N'-(2-(methylsulphonyl)phenyl)urea

N-(4-(6-cyano-7-(2-(methoxyethoxy)-4-chinolin)oxyphenyl)-N'-cyclopropylamine,

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(1,3-thiazol-2-yl)urea,

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-cyclopropylamine,

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)oxyphenyl)-N'-cyclopropanemethylamine,

N-(4-(6-cyano-7-(3-(morpholine-4-yl)propoxy)quinoline-4-yloxy)-2-forfinal)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-chinolin)oxyphenyl)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-chinolin)oxyphenyl)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(3-(methylsulphonyl)phenyl)urea

N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(3-(1-(4-ethylpiperazine))propoxy)-4-chinolin)oxyphenyl)-N'-(4-methoxyphenyl)urea,

N-(4-(6-cyano-7-(3-cyanopropyl)-4-chinolin)hydroxy-2-forfinal)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(2-(methylsulphonyl)ethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(2-(METI sulfonyl)ethoxy)-4-chinolin)oxyphenyl)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)oxyphenyl)-N'-phenylacetone,

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(3-methoxycarbonylpropionyl)-4-chinolin)oxyphenyl)-N'-(4-methoxyphenyl)urea,

N-(4-(6-cyano-7-(3-carboxypropyl)-4-chinolin)oxyphenyl)-N'-(4-methoxyphenyl)urea,

N-(4-(6-cyano-7-(2-(2-hydroxyethoxy)ethoxy)-4-chinolin)oxyphenyl)-N'-(4-methoxyphenyl)urea,

N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-hinomisaki)phenyl)-N'-(3-(methylsulphonyl)phenyl)urea

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-chinolin)oxyphenyl)-N'-(3-(methylsulphonyl)phenyl)urea

N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-hinomisaki)phenyl)-N'-phenylacetone,

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-chinolin)oxyphenyl)-N'-phenylacetone,

N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-chinolin)oxyphenyl)-N'-(2-oxo-1,2,3,4-tetrahydro-6-chinolin)urea

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)oxyphenyl)-N'-(3-acetamidophenyl)urea

N-(4-(6-cyano-7-benzyloxy-4-chinolin)hydroxy-2-forfinal)-N'-(2,4-differenl)urea

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(4-forfinal)urea

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-phenylacetone,

4-(4-((4-foronline)carbonyl)aminomethane is)-7-(2-methoxyethoxy)-6-chinainternational,

7-(2-methoxyethoxy)-4-(4-((1,3-thiazol-2-ylamino)carbonyl)aminophenoxy)-6-chinainternational,

4-(4-((anilinoacrolein)amino)-3-pertenece)-7-(2-methoxyethoxy)-6-chinainternational,

4-(4-((4-foronline)carbonyl)aminophenoxy)-7-methoxy-6-chinainternational,

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-chinainternational,

7-methoxy-4-(4-((1,3-thiazol-2-ylamino)carbonyl)aminophenoxy)-6-chinainternational,

4-(4-((2,4-diptiranjan)carbonyl)amino-3-pertenece)-7-methoxy-6-chinainternational,

4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-chinainternational,

4-(5-((anilinoacrolein)amino)-2-pyridyloxy)-7-methoxy-6-chinainternational,

4-(4-((anilinoacrolein)aminophenoxy)-7-methoxy-6-chinainternational,

4-(4-((anilinoacrolein)aminophenoxy)-7-(2-methoxyethoxy)-6-chinainternational,

4-(4-((2,4-diptiranjan)carbonyl)amino-3-pertenece)-7-(2-methoxyethoxy)-6-chinainternational,

4-(4-((4-foronline)carbonyl)amino-3-pertenece)-7-(2-methoxyethoxy)-6-chinainternational,

7-(2-methoxyethoxy)-4-(4-((1,3-thiazol-2-ylamino)carbonyl)amino-3-pertenece)-6-chinainternational and

4-(4-((4-foronline)carbonyl)amino-3-pertenece)-7-methoxy-6-chinainternational.

19. The compound according to claim 1 or 2, its Pharma is logicheskie acceptable salt or hydrate, where the specified compound chosen from:

N-(4-(6-cyano-7-(2-methoxyethoxy)-4-chinolin)hydroxy-2-forfinal)-N'-(4-forfinal)urea

N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-chinolin)oxy)phenyl)-N'-cyclopropylamine,

N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-chinolin)oxy)phenyl)-N'-(4-forfinal)urea

N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-chinolin)oxy)phenyl)-N'-(4-forfinal)urea

N-{4-[6-cyano-7-(2-hydroxy-3-pyrrolidin-1 ipropose)quinoline-4-yloxy]-2-were}-N'-4-cyclopropylamine,

4-(4-(4-foronline)carbonyl)-4-methylaminophenol)-7-methoxy-6-chinainternational,

4-(3-chloro-4-(cyclopropanecarbonyl)aminophenoxy)-7-methoxy-6-chinainternational,

4-(3-chloro-4-(cyclopropanecarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-chinainternational,

N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

N6-(2-pyridyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

N6-(2-foradil)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

N6-methoxy-4-(3-chloro-4-(((cyclopropa is amino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

6-carbarnoyl-4-(1-ethylcarbamate-1H-indol-5-yloxy)-7-methoxyquinoline,

6-carbarnoyl-7-methoxy-4-(1-propellerblades)-1H-indol-5-yloxy)quinoline,

6-carbarnoyl-7-methoxy-4-[1-(1-methyl)ethylcarbamate-3-H-indol-5-yloxy]quinoline,

N4-(4-{4-[(anilinoacrolein)amino]-3-chlorophenoxy}-2-pyridyl)-1-methyl-4-piperazinecarboxamide,

N1-phenyl-3-chloro-5-[(2-{[(1-methyl-4-piperidyl)carbonyl]amino}-4-pyridyl)oxy]-1H-1-indocarbocyanine,

N4-[4-(3-chloro-4-{[(4-foronline)carbonyl]amino}phenoxy)-2-pyridyl)]-1-methyl-4-piperazinecarboxamide,

1-(2-chloro-4-{6-[4-(2-diethylaminoethoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yloxy}phenyl)-3-cyclopropylamine,

1-{2-chloro-4-[6-[4-((2R)-2-hydroxy-3-diethylaminopropyl)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yloxy]phenyl}-3-cyclopropylamine,

1-(2-chloro-4-{6-[4-((2R)-2-hydroxy-3-pyrrolidinyloxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yloxy}phenyl)-3-cyclopropylamine and

1-(2-chloro-4-{6-[4-(2-diethylaminoethoxy)phenyl]-7H-pyrrolo[2,3-d]pyrimidine-4-yloxy}phenyl)-3-cyclopropylamine.

20. The compound according to claim 1 or 2, its pharmacologically acceptable salt or hydrate, where the specified connection is selected from the:

4-(3-chloro-4-(cyclopropanecarbonyl)aminophenoxy)-7-methoxy-6-chinainternational,

4-(3-chloro-4-(ethylaminomethyl)aminophenoxy)-7-methoxy-6-chinainternational,

N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational,

4-(3-chloro-4-(methylaminomethyl)aminophenoxy)-7-methoxy-6-chinainternational and

N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational.

21. The compound according to claim 1 or 2, its pharmacologically acceptable salt or hydrate, where the specified compound is 4-(3-chloro-4-(cyclopropanecarbonyl)aminophenoxy)-7-methoxy-6-chinainternational.

22. The compound according to claim 1 or 2, its pharmacologically acceptable salt or hydrate, where the specified compound is 4-(3-chloro-4-(ethylaminomethyl)aminophenoxy)-7-methoxy-6-chinainternational.

23. The compound according to claim 1 or 2, its pharmacologically acceptable salt or hydrate, where the specified compound is N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational.

24. The compound according to claim 1 or 2, its pharmacologically acceptable salt or hydrate, where the specified compound is N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-chinainternational.

25. The compound according to claim 1 or 2, farmakol the cally acceptable salt or hydrate, where the specified compound is 4-(3-chloro-4-(methylaminomethyl)aminophenoxy)-7-methoxy-6-chinainternational.

26. Drug, inhibiting angiogenesis and containing as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

27. Pharmaceutical composition having inhibitory activity against angiogenesis, the specified composition as the active ingredient contains a compound according to claim 2, its pharmacologically acceptable salt or hydrate, together with a pharmacologically acceptable carrier.

28. Preventive or therapeutic agent for the treatment of diseases against which it is effective inhibition of angiogenesis, containing as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

29. Angiogenesis inhibitor containing as an active ingredient the compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

30. Antitumor agent containing as an active ingredient the compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

31. Therapeutic agent for the treatment of angiomas, containing as active ingredient a compound according to any one of claims 1 and 2, it farmakologicheskaya salt or hydrate.

32. Inhibitor of metastasis of a cancer comprising as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

33. Therapeutic agent for the treatment of revascularization of the retina or diabetic retinopathy, containing as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

34. Therapeutic agent for treating inflammatory diseases, comprising as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

35. Therapeutic agent for the treatment of inflammatory diseases selected from deforming arthritis, rheumatoid arthritis, psoriasis and hypersensitivity of the delayed type, containing as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

36. Therapeutic agent for treatment of atherosclerosis, containing as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

37. Therapeutic agent for pancreatic cancer, stomach cancer, colon cancer, breast cancer, prostate cancer, lung cancer, kidney cancer, brain tumor, blood cancer or cancer of the ovary, sod is Rashi as an active ingredient the compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

38. Antitumor agent, which inhibits angiogenesis and containing as active ingredient a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

39. Prophylactic or therapeutic method of treating diseases against which it is effective inhibition of angiogenesis, providing for the introduction to the patient a pharmacologically effective dose of a compound according to any one of claims 1 and 2, its pharmacologically acceptable salt or hydrate.

40. The use of compounds according to claim 1 or 2, its pharmacologically acceptable salt or hydrate for the manufacture of a prophylactic or therapeutic agent for the treatment of diseases against which it is effective inhibition of angiogenesis.

Priority points and features:



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel biologically active compounds. Invention describes compounds or their salts of the general formula (I): A-B-N(O)s (I) wherein s = 2; A means R-T1- wherein R represents radical of a medicinal substance under condition that a medicinal substance by the formula R-T1-Z or R-T1-OZ wherein Z represents hydrogen atom (H) or (C1-C5)-alkyl is taken among paracetamol, salbutamol, ambroxol, alendronic acid,, cetirizine, ampicillin, aciclovir, doxorubicin, simvastatin, diphylline, tacrine, clopidogrel, dimethylomeprazol, diclofenac, ferulic acid, enalapril, propranolol, benfurodil hemisuccinate, tolrestate or sulindac; T1 means (CO), oxygen atom (O) or NH; B means TB-X2-O- wherein TB means bivalent radical R1B-X-R2B wherein R1B and R2B are similar or different and represent linear or branched (C1-C6)-alkylenes and X represents a bond, oxygen (O), sulfur (S) atom or NR1C wherein NR1C represents hydrogen atom (H) or linear or branched (C1-C6)-alkyl; corresponding precursor B is represented by the formula -TB-X2-OH wherein TB means (CO) and free valence in TB represents -OZ wherein Z is determined above, or TB means oxygen atom (O), and free valence in TB represents hydrogen atom (H) under condition that in the formula (I) when X2 in precursor B represents linear or branched (C2-C20)-alkylene then a medicinal substance by the formula R-T1-Z or R-T1-OZ used in the formula (I) doesn't belong to the following substances: enalapril (ACE inhibitors) and diclofenac (NSAID). Also, invention describes pharmaceutical compositions for using in cases of oxidative stress and 4-nitroxybutanoic acid 4'-acetylaminophenyl ester. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of medicinal substances and compositions.

7 cl, 8 tbl, 32 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to 2-aminomethylthieno[2,3-d]pyrimidines of the general formula (I): wherein R1 and R2 in common with C-atoms with which they are bound form 5-7-membered monounsubstituted cycloalkenyl ring; R3 and R4 are similar or different and represent independently of one another (C1-C8)-alkoxy-group or halogen atom; R5 and R6 can be similar or different and represent independently of one another hydrogen atom, linear or branched (C1-C8)-alkyl group that can be substituted with one or more hydroxyl, (C1-C8)-alkoxy-group, amine, mono-(C1-C8-alkyl)-amine or di-(C1-C8-alkyl)-amine groups, or in common with nitrogen atom to which they are bound form a heterocyclic ring that comprises optionally one or more additional nitrogen atoms and substituted with one or more hydroxyl, (C1-C8)-alkoxy- or (C1-C8)-alkylol groups. Compounds elicit the inhibitory effect with respect to activity of phosphodiesterase V and can be used in treatment of cardiovascular system states and in disturbance in the potency injury. Also, invention describes a medicinal preparation based on compounds said, a method for its preparing and a method for preparing compounds.

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

6 cl, 1 tbl, 16 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to substituted pyridines and pyridazines with angiogenesis inhibition activity of general formula I

(I)1, wherein ring containing A, B, D, E, and L represents phenyl or nitrogen-containing heterocycle; X and Y are various linkage groups; R1 and R2 are identical or different and represent specific substituents or together form linkage ring; ring J represents aryl, pyridyl or cycloalkyl; and G's represent various specific substituents. Also disclosed are pharmaceutical composition containing claimed compounds, as well as method for treating of mammalian with abnormal angiogenesis or treating of increased penetrability using the same.

EFFECT: new pyridine and pyridazine derivatives with angiogenesis inhibition activity.

26 cl, 6 tbl, 114 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (1)

wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

26 cl, 1 tbl, 119 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of piperazine of the general formula (I): wherein Y represents lower alkylene; R1 represents phenyl substituted with one or two similar or different substitutes taken among a group including lower alkoxy-group, mono- (or di-, or tri-)-halogen-lower)-alkyl, nitro-, amino-, lower alkylamino-, di-(lower)-alkylamino-, lower alkylthio-group,alkylsulfonyl, lower alkylaminosulfonyl, di-(lower)-alkylaminosulfonyl, and pyrrolyl; R2 means phenyl substituted with hydroxy-group at position 3 and with lower alkyl and halogen atom additionally; R3 means hydrogen atom; R4 represents (2,6-dimethylmorpholino)-(lower)-alkyl, (2-methoxymethylmorpholino)-(lower)-alkyl, (3-methoxymethylmorpholino)-(lower)-alkyl. Also, invention relates to their pharmaceutically acceptable salts, to method for their preparing, pharmaceutical composition and a method for vomiting inhibition. Proposed compounds are antagonists of tachykinin and can be used for vomiting inhibition.

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

9 cl, 47 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new oxathiepino[6,5-b]dihydropyridines of the formula (I):

wherein: (a) R1, R2, R3, R4 and R5 are taken independently among group consisting of hydrogen atom (H), halogen atom, nitro-group (NO2); (b) R6 is taken among group consisting of unbranched or branched (C1-C5)-alkyl wherein indicated alkyl can be substituted with phenylacetyloxy-, hydroxy- carboalkoxy-group or group NR'R'' wherein R' and R'' are taken independently among group consisting of hydrogen atom (H), unbranched or branched (C1-C8)-alkyl, benzyl; (c) R7 is taken among group consisting of hydrogen atom (H), alkyl; (d) R9 represents oxygen atom; (e) n is a whole number from 1 to 2, or its pharmaceutically acceptable salt. Compounds are useful as antagonists of calcium channels and elicit cardiovascular, anti-asthmatic and anti-bronchoconstricting activity. Also, invention describes the pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds and composition.

28 cl, 2 tbl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

FIELD: organic chemistry, medicine, hormones, pharmacy.

SUBSTANCE: invention relates to new biologically active compounds that act as agonists of peptide hormone vasopressin. Invention describes the compound of the general formula (1) or its pharmaceutically acceptable salt wherein V represents a covalent bond or NH; X is taken among CH2, oxygen atom (O) and N-alkyl; Z represents sulfur atom (S) or -CH=CH-; R1 and R2 are taken independently among hydrogen (H), fluorine (F), chlorine (Cl), bromine (Br) atom and alkyl; R3 is taken among hydroxyl group (OH), O-alkyl and NR4R5 wherein each R4 and R5 represents independently hydrogen atom (H) or alkyl, or both represent -(CH2)q-; p = 0, 1, 2, 3 or 4; q = 4 or 5. Also, invention describes a pharmaceutical composition eliciting agonistic activity with respect to V2-receptors, a method for treatment of enuresis, nicturia and diabetes insipidus, method for control of enuresis and a method for treatment of enuresis and a method for treatment of diseases associated with damage in blood coagulability. Invention provides preparing new compounds eliciting useful biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 31 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry, peptides, medicine, pharmacy.

SUBSTANCE: invention relates to peptide derivatives named as memnopeptides that are used as an active component for manufacturing a medicinal preparation used in treatment of bacterial infection. Invention proposes compound of the formula (I): wherein radicals R1, R2, R3, R4, R5, R6, R7, R8 and (A)n have corresponding values, or its salt. Compounds of the formula (I) are prepared by culturing microorganism Memnoniella echinata FH 2272, DSM 13195 under suitable conditions in the nutrient medium containing at least one source of carbon atoms and at least one source of nitrogen atoms and the process is carrying out until the accumulation of at least one compound of the formula (I) in the nutrient medium followed by isolation of indicated compound. The attained technical result involves the development of a pharmaceutical composition eliciting an antibacterial activity. The development of the preparation provides expanding assortment of agents used in treatment of diseases said above.

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

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

The invention relates to derivatives of 6-sulfamoylbenzoic-4-carboxylic acid of formula (1), where R1, R2, R3and R4such as defined in the claims

3-piperidine, methods for their preparation and pharmaceutical composition based on them" target="_blank">

The invention relates to tricyclic3-piperidinol General formula (1), where X is O or S, R1means hydrogen, halogen, C1-6alkyl or C1-4alkyloxy, Alk means C1-6alcander, a D such as defined in the claims

The invention relates to a new 1.8-fused derivative of 2-Hinayana formula (I), where A, X, R1, R2, R3, R4, R5, R6such as defined in the claims

The invention relates to compounds which inhibit the protease encoded by human immunodeficiency virus, or their pharmaceutically acceptable salts, and such compounds are used for the prevention of infection by HIV, treating infection by HIV and the treatment of acquired as a result immunodeficiency syndrome (AIDS)

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel biologically active compounds. Invention describes compounds or their salts of the general formula (I): A-B-N(O)s (I) wherein s = 2; A means R-T1- wherein R represents radical of a medicinal substance under condition that a medicinal substance by the formula R-T1-Z or R-T1-OZ wherein Z represents hydrogen atom (H) or (C1-C5)-alkyl is taken among paracetamol, salbutamol, ambroxol, alendronic acid,, cetirizine, ampicillin, aciclovir, doxorubicin, simvastatin, diphylline, tacrine, clopidogrel, dimethylomeprazol, diclofenac, ferulic acid, enalapril, propranolol, benfurodil hemisuccinate, tolrestate or sulindac; T1 means (CO), oxygen atom (O) or NH; B means TB-X2-O- wherein TB means bivalent radical R1B-X-R2B wherein R1B and R2B are similar or different and represent linear or branched (C1-C6)-alkylenes and X represents a bond, oxygen (O), sulfur (S) atom or NR1C wherein NR1C represents hydrogen atom (H) or linear or branched (C1-C6)-alkyl; corresponding precursor B is represented by the formula -TB-X2-OH wherein TB means (CO) and free valence in TB represents -OZ wherein Z is determined above, or TB means oxygen atom (O), and free valence in TB represents hydrogen atom (H) under condition that in the formula (I) when X2 in precursor B represents linear or branched (C2-C20)-alkylene then a medicinal substance by the formula R-T1-Z or R-T1-OZ used in the formula (I) doesn't belong to the following substances: enalapril (ACE inhibitors) and diclofenac (NSAID). Also, invention describes pharmaceutical compositions for using in cases of oxidative stress and 4-nitroxybutanoic acid 4'-acetylaminophenyl ester. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of medicinal substances and compositions.

7 cl, 8 tbl, 32 ex

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