Derivatives of indole, having antiviral activity

 

The invention relates to new indole derivative of the formula Iin which R¹is hydrogen, (NISS. )alkyl, (NISS. )alkylsulfonyl, optionally substituted aryl, optionally substituted aryl(NISS. )alkyl, C₃-C₆cycloalkyl(NISS. )alkyl, morpholinyl(NISS. )alkyl, sulfamoyl, optionally substituted lower alkyl, carbarnoyl, optionally substituted lower alkyl or phenyl, lower alkylsulfonyl, morpholinylcarbonyl, thienyl(NISS. )alkyl, optionally substituted lower alkoxycarbonyl or carboxyla, pyridyl(NISS. )alkyl, optionally substituted phenylsulfonyl, thienylmethyl, phenylcarbinol, lower alkoxycarbonyl; R²is hydrogen, optionally substituted phenyl, optionally substituted phenyl(NISS. )alkyl, phenylcarbamoyl, lower alkyl, optionally substituted phenylsulfonyl, optionally substituted phenylsulfinyl, morpholino(NISS. )alkyl despite the fact that each of these substituted phenyl groups may carry substituents selected from halogen, trialsandrea lower alkyl, lower alkoxyl, azido, nitro, amino, phenyl, lower alkoxycarbonyl, amino (substituted lower alkyl or lower alkylcarboxylic), Renny (NISS. )alkyl, hydroxy, (NISS. )alkoxy, nitro, phenylsulfonyl, phenyl(NISS. )alkoxy, carboxy, NISS. alkoxycarbonyl, optionally substituted by phenyl; X is hydroxy, amino, optionally substituted lower alkyl or lower alkoxy(NISS. )alkyl; Y is - COOR (where R is hydrogen, lower alkyl, optionally substituted phenyl), tetrazolyl, optionally substituted Triticum, imidazolyl, triazolyl, thiazolyl, pyrazolyl, phenyl, optionally substituted by carboxypropyl, lower alkoxyl or hydroxy-group; provided that excluded the compounds in which each of R¹- R⁶is hydrogen, R⁴is hydroxy, and Y is SOOS₂H₅their tautomers, pharmaceutically acceptable salts or hydrates, which have the integrase inhibitory activity, which allows their use in pharmaceutical compositions against HIV infection. 3 S. and 13 C. p. F.-ly, 16 PL.

Description text in facsimile form (see graphic part)

Claims

1. Derivatives of indole of the formula

in which R¹means hydrogen, (ness.)alkyl, (ness.)alkylsulfonyl, optionally substituted aryl, optionally substituted aryl(ness.)Ala is PWM-alkyl, carbarnoyl, optionally substituted lower alkyl or phenyl, lower alkylsulfonyl, morpholinylcarbonyl, thienyl(ness.)alkyl, optionally substituted lower alkoxycarbonyl or carboxyla, pyridyl(ness.)alkyl, optionally substituted phenylsulfonyl, thienylmethyl, phenylcarbinol, lower alkoxycarbonyl;

R²means hydrogen, optionally substituted phenyl, optionally substituted phenyl(ness.)alkyl, phenylcarbamoyl, lower alkyl, optionally substituted phenylsulfonyl, optionally substituted phenylsulfinyl, morpholino(ness.) alkyl, despite the fact that each of these substituted phenyl groups may carry substituents selected from halogen, trialsandrea lower alkyl, lower alkoxyl, azido, nitro, amino, phenyl, lower alkoxycarbonyl, amino (substituted lower alkyl or lower alkylcarboxylic), aryl(ness.)of alkyl, NISS.of alkyl, carboxyl;

R³, R⁴, R⁵and R⁶each independently mean hydrogen, halogen, trigosamine (ness.)alkyl, hydroxy, (ness.)alkoxy, nitro, phenylsulfonyl, phenyl(ness.)alkoxy, carboxy, NISS.alkoxycarbonyl, optionally substituted by phenyl;

X is hydroxy, amino, optional replacement is optionally substituted by phenyl), tetrazolyl, optionally substituted Triticum, imidazolyl, triazolyl, thiazolyl, pyrazolyl, phenyl, optionally substituted by carboxypropyl, lower alkoxyl or hydroxy-group;

provided that excluded the compounds in which each of R¹, R², R³, R⁵and R⁶means hydrogen, R⁴means hydroxy, and Y means SOOS₂H₅,

their tautomers, pharmaceutically acceptable salts or hydrates.

2. Connection on p. 1, where R¹and R²at the same time does not mean hydrogen when Y is a COOR (where R has the above value).

3. Connection on p. 1, where R¹and R²at the same time does not mean hydrogen, when X represents hydroxy and Y represents COOR (where R has the above value).

4. The compound according to any one of paragraphs.1-3, where R¹means hydrogen or optionally substituted phenylsulfonyl.

5. The compound according to any one of paragraphs.1-3, where R²means hydrogen, optionally substituted phenyl or optionally substituted phenyl(ness.)alkyl.

6. The compound according to any one of paragraphs.1-3, where each of R¹, R², R³and R⁵and R⁶independently from each other represents a hydrogen or halogen.

7. Connection on p. 6, where X is a hydroxy-group.

9. Connection on p. 1, where Y means triazolyl, tetrazolyl, optionally substituted Triticum, imidazolyl, thiazolyl or pyrazolyl.

10. The compound according to any one of paragraphs.1-3, where R¹means hydrogen or optionally substituted phenylsulfonyl, R²means hydrogen, optionally substituted phenyl or optionally substituted phenyl(ness.)alkyl, R³, R⁴, R⁵and R⁶each independently of one another denotes hydrogen or halogen, and X is a hydroxy-group.

11. The compound according to any one of paragraphs.1-3, where R¹means hydrogen or optionally substituted phenylsulfonyl, R²means hydrogen, optionally substituted phenyl or optionally substituted phenyl(ness.)alkyl, R³, R⁴, R⁵and R⁶each independently of one another denotes hydrogen or halogen, X is hydroxy and Y means tetrazolyl, thiazolyl or imidazolyl.

12. The compound according to any one of paragraphs.1-3, where R¹means hydrogen or optionally substituted phenylsulfonyl, R²means hydrogen, optionally substituted phenyl or optionally substituted phenyl(ness.)alkyl, the radicals R³, R⁴, R⁵and R⁶each independently mean hydrogen or halogen, X is gidrol, R²means hydrogen, optionally substituted phenyl(ness.)alkyl, the radicals R³, R⁴, R⁵and R⁶each independently mean hydrogen or halogen, X is a hydroxy-group, and Y denotes tetrazolyl, optionally substituted Triticum, imidazolyl, triazolyl, thiazolyl or pyrazolyl.

14. Connection on p. 13, where R¹means hydrogen or phenylsulfonyl, optionally substituted with halogen, R²means hydrogen, optionally substituted by halogen phenyl or phenylmethyl, optionally substituted with halogen, R⁴denotes halogen, the radicals R³, R⁵and R⁶all at the same time signify hydrogen, X signifies a hydroxy-group, a Y indicates tetrazolyl.

15. Pharmaceutical composition containing as active ingredient a derivative of indole according to any one of paragraphs.1-14 and intended for inhibiting integrase.

16. Pharmaceutical composition containing as active ingredient a derivative of indole according to any one of paragraphs.1-14 acting against HIV infection.