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.