Bicyclic derivatives, pharmaceutical compositions on their basis and intermediate compounds

 

The invention relates to the field of organic chemistry, namely to new bicyclic derivatives. Describes bicyclic derivatives of General formula (I)where R1denotes pyrimidinyl or pyridyl, each optionally substituted independently with one, two or three substituents selected from alkyl, alkoxy, alkylthio, halogen, nitro, hydroxyamino, -NRR' (where R and R' independently of one another denote hydrogen, alkyl, carboxylic or heteroalkyl) or-NHC(0)Rb[where Rbmeans alkyl, -(alkylene)-X, where X is alkoxy, alkylamino, dialkylamino, heterocyclyl or heteroaryl], --- refers to the relationship between or and CR1or Q and CR1, as a result, (I) when --- indicates the relationship between Q and CR1then denotes nitrogen, R2denotes haloethanol or pyridyl, and Q represents-CH-, and (II) when --- indicates the relationship between V and CR1then In the refers to carbon, R2denotes phenyl, optionally substituted by halogen, alkyl, alkoxy or haloalkyl, and Q represents-NR4- or-O-, where R4denotes hydrogen, alkyl, haloalkyl, heteroalkyl, heteroalkyl, geterotsiklicheskikh, -OR5(where R5denotes hydrogen, alkyl, gets the e denotes a cyano; -COOR7where R7denotes hydrogen or alkyl, -CONR8R9where R8denotes hydrogen or alkyl, R9denotes hydrogen, alkyl, alkoxy or -(alkylene)-R7; -C(=NH)NH2; or,- COR13where R13denotes alkyl, denotes a group of the formula (S), (T), (U), (V) or (W)where R6denotes hydrogen, alkyl, heteroalkyl, halogen, alkoxy, monoalkylamines (optionally substituted by hydroxy, alkoxy or amino), dialkylamino, alkylthio, -NHC(O)R" [where R" denotes an alkyl], and R3denotes hydrogen, alkyl, haloalkyl; and "alkyl" and "alkylene" in all cases and "alkoxy" each contain not more than six carbon atoms; "heteroalkyl" denote an alkyl group containing not more than six carbon atoms and having one or two substituent selected from hydroxy, hydroxyalkyl, alkoxy, alkylthio, -NRaRband SO3X+where Rameans hydrogen, alkyl, hdroxy, cianelli, hydroxyalkyl, aminoalkyl or dialkylaminoalkyl, and X+means an alkali metal atom; "heteroaryl" refers to imidazoline radical, containing from 3 to 8 ring atoms in which 1 or 2 ring atoms are heteroatoms selected from N and O and which may be substituted by one or two substituents, independently selected from alkyl, hydroxyalkyl, hydroxy, amino and carbamoyl, as well as their pharmaceutically acceptable salts, individual isomers and mixture of isomers. Also describes a pharmaceutical composition based on compounds of the formula (I) intended for the treatment and prevention of inflammatory diseases, and intermediate compounds. The technical result obtained new compounds with useful biological properties. 3 S. and 12 C.p. f-crystals, 8 PL.

Description text in facsimile form (see graphic part)

Claims

1. Bicyclic compounds selected from the group of compounds of formula (I)

(I)

in which R1- pyrimidinyl or pyridyl, each optionally substituted independently with one, two or three substituents selected from alkyl, alkoxy, alkylthio, halogen, nitro, hydroxylamino, -NRR' (where R and R' independently of one another denote hydrogen, alkyl, carboxylic or heteroalkyl) or-NHC(Rila];

--- refers to the relationship between or and CR1or Q and CR1owing to what,

(I) when --- indicates the relationship between Q and CR1then In nitrogen,

R2denotes haloethanol or pyridyl, and

Q is-CH-, and (II) when --- indicates the relationship between V and CR1then - carbon, R2is phenyl, optionally substituted by halogen, alkyl, alkoxy or haloalkyl, and Q represents-NR4- or-O-,

where R4is hydrogen, alkyl, haloalkyl, heteroalkyl, heteroalkyl, geterotsiklicheskikh, -OR5(where R5is hydrogen, alkyl, heteroalkyl or geterotsiklicheskikh), -SO2R" (where R" is alkyl), -(alkylene)-Z or -(alkylene)-CO-(alkylene)-Z, where Z is cyano; -OOR7where R7denotes hydrogen or alkyl, -CONR8R9where R8is hydrogen or alkyl, R9is hydrogen, alkyl, alkoxy or -(alkylene)-R7; - C(=NH)NH2or-COR13where R13- alkyl,

group of the formula (S), (T), (U), (V) or (W)

or

where R6is hydrogen, alkyl, heteroalkyl, halogen, alkoxy, monoalkylamines (it is adored, alkyl, haloalkyl;

the "alkyl" and "alkylene" all connections and "alkoxy" each contain not more than six carbon atoms;

"heteroalkyl" denote an alkyl group containing not more than six carbon atoms and having one or two substituent selected from hydroxy, hydroxyalkyl, alkoxy, alkylthio, -NRaRband-SO3X+where Rais hydrogen, alkyl, hydroxy, cianelli, hydroxyalkyl, aminoalkyl or dialkylaminoalkyl and Rbis hydrogen, alkyl, hydroxyalkyl, aminoalkyl or dialkylaminoalkyl, X+the alkali metal atom;

"heteroaryl" refers to imidazolidinyl group which may be substituted by alkyl or nitro;

"heterocyclyl" refers to cyclic saturated organic radical containing from 3 to 8 ring atoms in which 1 or 2 ring atoms are heteroatoms selected from N and O and which may be substituted by one or two substituents, independently selected from alkyl, hydroxyalkyl, hydroxy, amino and carbamoyl;

and their pharmaceutically acceptable salts, individual isomers and mixture of isomers.

2. Connection on p. 1, in which R6is hydrogen, alkyl, halogen, alkoxy, monoalkylamines (optionally substituted Hydra is ormula (Ia)

in which R1, R2and R3have the values listed in paragraph 1;

Q represents-NR4- or-O-, where R4matter specified in paragraph 1, except-SO2R";

one of a and D is a nitrogen atom and the other represents-CR6- where R6is hydrogen, alkyl, halogen, alkoxy, monoalkylamines (optionally substituted by hydroxy, alkoxy or amino), dialkylamino or heteroalkyl,

and their pharmaceutically acceptable salts, individual isomers and mixture of isomers.

4. Connection under item 1 or 2, wherein --- represents a relationship between In-CR1-,represents a group of formula (S), (V) or (W), and Q represents-NR4-.

5. Connection on p. 1, 2 or 4, in which R1denotes 4-peregrinae or 4-pyrimidinyl ring, optionally substituted by a Deputy selected from-NRR' (where each R and R' independently from each other hydrogen, alkyl or heteroalkyl) and-NHC(O)Rb[where Rb- alkyl or -(alkylene)-X, where X is alkoxy, alkylamino, dialkylamino, heterocyclyl or heteroaryl].

6. Connection on p. 1, 2, 4, or 5, in which R2denotes phenyl ring, optionally substituted by one or two substituents selected from Oh, fluorine or chlorine, and R1- 4-peregrinae ring, optionally substituted in the 2-position of Deputy selected from amino, methylamino-, dimethylamino-, acetylamino-, 2-hydroxyethylamino-, 3-hydroxypropylamino-, 2-aminoethylamino and methoxypropyl.

8. The compound according to any one of paragraphs. 1, 2 and 4-7, in which R6is hydrogen, R2is a phenyl ring substituted by one or two substituents selected from methyl, fluorine, chlorine and methoxy, and R3is hydrogen, methyl, chlorine or fluorine.

9. The compound according to any one of paragraphs. 1, 2 and 4-8, in which R4is hydrogen, methyl, ethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-amino-ethyl, 3-aminopropyl, 2-methylaminomethyl, 3-methylaminopropyl, 2-dimethylaminoethyl, 3-dimethylaminopropyl, 2 - (morpholine - 4 - yl) ethyl, 3 - (morpholine - 4 - yl) propyl,

2-(piperidine-1-yl)ethyl, 3-(piperidine-1-yl) propyl, 2-(piperazine-1-yl)ethyl, 3-(piperazine-1-yl)propyl, hydroxyl, methoxy, 2-hydroxyethoxy, 3 hydroxypropoxy, 2-methylaminoethanol, 3 methylaminopropane, 2-dimethylaminoethoxy, 3 dimethylaminopropoxy, 2-(morpholine-4-yl)ethoxy, 3-(morpholine-4-yl)propoxy, 2-(piperidine-1-yl)ethoxy, 3-(piperidine-1-yl)propoxy, 2-(piperazine-1-yl)ethoxy or 3-(piperazine-1-yl)propoxy.

10. Compounds according to any one of paragraphs. 1 and 4-9, the selected 3-(4-forfinal)-2-[2- (2-hydroxyine.

11. Compounds according to any one of paragraphs. 2 and 4-9, selected from 3-(4-forfinal)-1-methyl-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine and 7-(4-forfinal) -6- (pyridin-4-yl) -5H-pyrrolo [2,3-b] pyrazine.

12. Compounds according to any one of paragraphs. 3-9 selected from 3-(4-forfinal)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, 3-(4-forfinal)-1-methoxy-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, 3-(4-forfinal)-1-[2-(morpholine-4-yl)ethoxy]-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, 3-(4-forfinal)-1-hydroxy-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, 3-(4-forfinal)-1-[2-(piperidine-1-yl)ethoxy]-2-(pyridin-4-yl)-lH-pyrrolo[3,2-b]pyridine, 3-(4-forfinal)-1-[2-(piperidine-1-yl)ethyl]-2-(pyridin-4-yl)-lH-pyrrole,2-b] pyridine and 3-(4-forfinal)-1-[2-(morpholine-4-yl)ethyl] -2- (pyridin-4-yl) -1H-pyrrolo [3,2-b] pyridine.

13. Compounds according to any one of paragraphs. 1-12, intended for use as pharmaceutically active substances, in particular for the treatment of inflammatory diseases.

14. Compounds of formulas

where Y is halogen, Z is-NH-CR1=chr2or

Y-COR2and Z is-NH-COR1or

Y is a hydrogen atom and Z-NHN=CR1-CH2R2; or

Y represents-C=CR1and Z denotes-other2;

R1and R2matter, uki inert carrier and intended primarily for the treatment and prevention of inflammatory diseases.

Priority items:

20.10.1997 on p. 3;

20.02.1998 on PP.1-2, 4-9, 13-16;

18.08.1998 on PP.10-12.

 

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