Derivatives of indole, drug, containing the retrieval method (variants)

 

The invention relates to inhibitors tyrosinekinase type bis-indolylmaleimide compounds of the formula Iwhere Z denotes a group of General formula IIwhere A, B, X, Z, R1-R10have the meanings indicated in the claims, as well as the way they are received and medicinal product on the basis of these compounds. The technical result - the acquisition of new inhibitors. 4 C. and 6 C. p. F.-ly, 2 tab.

Description text in facsimile form (see graphic part)I

Claims

1. Derivatives of indole of General formula

where Z denotes a group of General formula II

where a represents a nitrogen atom, oxygen or sulfur;

In the atom of nitrogen, oxygen, or sulfur, provided that a and b cannot be both oxygen atoms;

X denotes a group of General formula III or IV

where l and n may denote a number from 0 to 6;

m is the number 1 or 2;

R14and R15or both together mean an oxygen atom, or R14means a hydroxyl group, and R15means ATO is the residue substituted with halogen, amino or sidegroups alkyl residue, alkyloxyalkyl residue or substituted alkyloxyalkyl balances;

R2and R13combined with the formation of the structure of the General formula V

where the dotted line means a double or a simple bond;

R16has the above meanings;

R2and R13mean the same or different residues of the General formula VII

where the dotted line means a double or a simple bond;

R16has the above meaning;

R17means a halogen atom or the residue of General formula VIII

where p can be 0, 1 or 2 (if p is 0, then we are talking about acyclic primary Amina and Y includes an additional hydrogen atom);

Y can mean a carbon atom, oxygen or nitrogen, and if Y denotes the carbon atom or nitrogen, R18means hydrogen or alkyl, or phenyl residue, substituted alkyl or phenyl residue, piperidinyl, alkoxycarbonyl, aminocarbonylmethyl, substituted aminocarbonylmethyl;

R2and R13combined with the formation of the structure of the General formula IX or X

could mean a number from 0 to 6;

R19and R20can denote hydrogen, alkyl or substituted alkyl residue,

where R1and R7may be the same or different and mean hydrogen, alkyl and aminoalkyl, phenylsulfonyl, alkyltrimethylenedi,-D-glyukopiranozil or-D-mannopyranosyl,

and R3, R4, R5, R6, R8, R9, R10and R11may be the same or different and chosen means hydrogen, alkyl, substituted by the following groups: alkoxy, amino, halogen, cycloalkyl, morpholinyl, piperidinyl, pyrrolidinyl, phenyl; alkoxy, alkoxymethyl group, a nitrogroup, halogen or O-alkoxygroup General formula-O-(CO)-R21and R21means alkyl substituted by the following groups: alkoxy, amino, halogen, phenyl, thienyl or furyl; alkoxy or alkoxymethyl; except bis(benzothiophen)methane.

2. Connection on p. 1, characterized in that they are represented by the General formula XI

where a represents a nitrogen atom;

In the mean nitrogen atoms, oxygen or sulfur;

R3, R4, R5, R6, R7, R8, R9, R10, R111and R2mean hydrogen atoms, a and b denote the nitrogen atom, a R1, R3, R4, R5, R6, R7, R8, R9, R10, R11and R16have the above values.

4. Connection on p. 1, characterized in that it is selected from the group consisting of the following compounds: basinda-2-Ilmatar-1-(5-methoxyindol-2-yl)(indol-2-yl)methane-1-he, bis(5-methoxyindol-2-yl)-1-methanon, benzo[b]thiophene-2-yl(5-methoxy-1H-2-indolyl)-1-methanon, 1H-2-indolyl[5-(2-morpholine-1-retracci)-1H-2-indolyl]metano, 1H-2-indolyl[5-(2-dimethylaminoethoxy)-1H-2-indolyl]metano, [2-(1H-2-indolyl-carbonyl)-1H-5-indolyl)]ethanoate, [2-(1H-2-indolocarbazole)-1H-5-indolyl)]butanoate, [2-(1H-2-indolocarbazole)-1H-5-indolyl)]-2-(N,N)-dimethylaminoethanol, [2-(1H-2-indolocarbazole)-1H-5-indolyl)]-propanoate, [2-(1H-2-indolocarbazole)-1H-5-indolyl)]-2-thiophenolate.

5. Connection at one PM.1-4 as a tyrosine kinase inhibitor.

6. Connection at one PM.1-4 as an inhibitor of PDGF-receptor tyrosine kinase or receptor-tyrosine kinase with similar structure.

7. Connection at one PM.1-4, with antitumor activity.

8. Drug, oblad is out on one of the PP.1-4.

9. The method of obtaining compounds under item 1, in which R2and R13mean residue of General formula V under item 1 or they merged to form the structure of the General formula VII under item 1, characterized in that 2,2'-bis-1H-intolerance or its derivative of General formula XI is treated with dibromomalonamide

where X, R1, R3, R4, R5, R6, R7, R8, R9, R10and R11have the above values.

10. The method of obtaining compounds under item 1, in which R2and R13combined with the formation of the structure of the General formula IX or X on p. 1, characterized in that the first process dibromomalonamide 2,2'-bis-1H-intolerance or its derivative of General formula XI

where X, R1, R3, R4, R5, R6, R7, R8, R9, R10and R11have the above values,

and then it is treated with a primary or secondary amine represented by the following General structures XVI, XVII or piperazine:

where p, q, R17and W have the above values.

 

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