DE4344452A1 - Aza-4-iminoquinolines, process for their preparation and their use - Google Patents

Description

The present invention relates to aza-4-iminoquinolines, process to their manufacture and use.

Compounds related to iminochinolines, but with others fused rings were in a publication from 1958 (M. Harfenist and E. Magnien, J. Amer. Chem. Soc. 1958, 80, 6080) as Mentioned intermediates in a synthesis. Describe further work the preparation of pyrrolo [3,2-c] quinolinones (T. Tanaka, N. Taga, M. Miyazaki and I. Iima, J.C.S. Perkin Trans. I 1974, 2110) and Isoxazolo [4,3-c] quinolinones (P. Roschger and W. Stadlbauer, Liebigs Ann. Chem. 1990, 821; ibid 1991, 401). A pharmacologically interesting activity however, has not yet been demonstrated for these compounds. Recently were pyrazolo [4,3-c] quinolinones (EP 0 476 544 A1) with anti-inflammatory Effect described.

It has surprisingly been found that the aza-4 described herein Iminochinolines of general formula I,

and their tautomeric forms of general formula Ia,

Ib and Ic

their optical isomers, diastereomers in pure form or in the form of their mixtures and their addition salts and prodrugs, an antiviral activity especially against retroviruses such as human immunodeficiency Virus "(HIV).  

In the compounds of the formula I, Ia, Ib or Ic according to the invention:
1) n zero, one, two or three,
the individual substituents R¹ independently of one another fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxy, mercapto, alkyl, cycloalkyl, alkoxy, alkoxy-alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, where the alkyl groups may be substituted by fluorine, chlorine , Hydroxy, amino, alkoxy, alkylamino, dialkylamino, acyloxy, acylamino, carboxy, aminocarbonyl, alkyloxycarbonyl;
Nitro, amino, azido, dialkylamino, piperidino, piperazino, N-methylpiperazino, morpholino, 1-pyrrolidinyl, acyl, acyloxy, acylamino, cyano, carbamoyl, carboxy, alkyloxycarbonyl, hydroxysulfonyl, sulfamoyl, or
a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, heteroaroyl or heteroaryl radical which is unsubstituted or substituted by up to five independent radicals R⁵,
where R⁵
Fluoro, chloro, bromo, iodo, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, azido, alkyl, cycloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkyloxycarbonyl, phenyl, phenoxy or heteroaryl,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X is oxygen, sulfur, selenium or substituted nitrogen N-R², where R² may have the meanings given below,
Y is [R⁶], O-R⁶, S-R⁶, N-R⁶R⁷, N =C-R⁶R⁷ or [C-R⁶R⁷R⁸], where R⁶, R⁷ and R⁸ may have the meanings given below,
R², R⁶, R⁷ and R⁸ may be identical or different and independently of one another hydrogen,
Alkyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Alkenyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Alkynyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Cycloalkyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Cycloalkenyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
(Cycloalkyl) - (alkyl), optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl;
(Cycloalkenyl) - (alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl;
Alkylcarbonyl optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Alkenylcarbonyl optionally substituted by fluoro, chloro or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkyl) carbonyl optionally substituted by fluoro, chloro or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkyl) - (alkyl) carbonyl, optionally substituted by fluoro, chloro or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkenyl) - (alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl;
Alkyloxycarbonyl optionally substituted by fluoro, chloro, bromo, hydroxy, alkoxy, alkylamino, dialkylamino, alkylthio;
Alkenyloxycarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkynyloxycarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkylthiocarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
Alkylamino and dialkylaminocarbonyl, optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkenylamino and dialkenylaminocarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxy, alkoxy, alkylthio, oxo, phenyl;
Alkenylsulfonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to five mutually independent radicals R⁵, wherein R⁵ is as defined above or substituted with up to three independent radicals R⁵ substituted heteroaryl, heteroarylalkyl, heteroarylalkenyl, Heteroarylalkylcarbonyl or Heteroarylalkenylcarbonyl, and
R³ and R⁴ are identical or different and independently of one another hydrogen,
Alkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
Alkenyl, optionally substituted by fluorine or chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
Cycloalkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl, cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxy, Amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl; or
with up to five mutually independent radicals R⁵ substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, where R⁵ is as defined above,
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring, optionally with fluorine, chlorine, hydroxyl, amino, alkyl, alkenyl, alkynyl, acyloxy, benzoyloxy, alkoxy, alkylthio, oxo, thioxo , Carboxy, carbamoyl or phenyl.

Suitable heteroatoms are in particular O, S, N, in which case a saturated N-containing ring N-Z at this point is present, wherein Z is H or R² means.

In a preferred group of compounds of the formula I, Ia, Ib or Ic:
2) n zero, one, or two
the individual substituents R¹ are independently fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, hydroxy, mercapto, C₁-C₆ alkyl, C₅-C₆-cycloalkyl, C₁-C₄ alkoxy, (C₁-C₄ alkoxy) - (C₁-C₂ -alkoxy), C₁-C₄-alkylthio, C₁-C₄-alkylsulfinyl, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylamino, wherein the alkyl groups may be substituted with fluorine, chlorine, hydroxyl, amino, carboxy, aminocarbonyl, C₁-C₄ alkyloxycarbonyl;
Amino, di (C₁-C₄-alkyl) amino, C₁-C₄-acyl, C₁-C₄-acyloxy, C₁-C₄-acylamino, cyano, carbamoyl, carboxy, (C₁-C₄-alkyl) -oxycarbonyl or
a phenyl, phenoxy, benzoyl, heteroaroyl or heteroaryl radical substituted by a radical R⁵,
where R⁵
Fluorine, chlorine, trifluoromethyl, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, may be,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X is oxygen, sulfur, selenium or substituted nitrogen N-R², where R² may have the meanings given below,
Y is [R⁶], O-R⁶, S-R⁶, N-R⁶R⁷, N =CR⁶R⁷ or [C-R⁶R⁷R⁸], where R⁶, R⁷ and R⁸ may have the meanings given below,
R², R⁶, R⁷ and R⁸ may be identical or different and independently of one another hydrogen,
C₁-C₈-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₂-C₈ alkenyl, optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ alkoxy, C₁-C₆ alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₃-C₈-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₃-C₈cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₅-C₈cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
(C₃-C₈cycloalkyl) - (C₁-C₄alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ Alkoxy, C₁-C₆alkylamino, di (C₁-C₆alkyl) amino, C₁-C₆alkylthio, C₁-C₆alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
(C₅-C₈cycloalkenyl) - (C₁-C₄-alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ Alkoxy, C₁-C₆alkylamino, di (C₁-C₆alkyl) amino, C₁-C₆alkylthio, C₁-C₆alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₁-C₆-alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₂-C₈ alkenylcarbonyl optionally substituted by fluoro, chloro or hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
(C₃-C₈cycloalkyl) carbonyl, optionally substituted by fluoro, chloro or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
(C₅-C₈cycloalkenyl) carbonyl optionally substituted by fluoro, chloro or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
(C₃-C₈cycloalkyl) - (C₁-C₃alkyl) carbonyl, optionally substituted by fluoro, chloro or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
(C₅-C₆cycloalkenyl) - (C₁-C₃alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
C₁-C₈-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄alkylthio;
C₂-C₈ alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₂-C₈ alkynyloxycarbonyl optionally substituted by fluoro, chloro, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₁-C₈-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
C₂-C₈ alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₁-C₈-alkylamino and di (C₁-C₈-alkyl) aminocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
C₂-C₈ alkenylamino and di (C₁-C₆ alkenyl) aminocarbonyl optionally substituted by fluoro, chloro, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₁-C₆-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, phenyl;
C₂-C₆ alkenylsulfonyl optionally substituted by fluoro, chloro, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to three independent radicals R⁵, wherein the alkyl radical may each contain 1 to 5 carbon atoms and R⁵ is as defined above
or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R⁵, where the alkyl radical can contain in each case 1 to 3 C atoms, and
R³ and R⁴ are identical or different and independently of one another hydrogen,
C₁-C₈-alkyl, optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy, carbamoyl;
C₂-C₈ alkenyl optionally substituted with fluorine or chlorine, hydroxy, amino, mercapto, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy, carbamoyl;
C₃-C₈cycloalkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy, carbamoyl;
C₃-C₈cycloalkenyl optionally substituted by fluorine or chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄alkoxy, C₁-C₄alkylamino, di (C₁-C₄alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy, carbamoyl;
with up to three mutually independent radicals R⁵ substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, wherein the alkyl radical may each contain 1 to 3 carbon atoms and R⁵ is as defined above,
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y may also be part of a saturated or unsaturated carbocyclic or heterocyclic ring having 3 to 8 carbon atoms, optionally substituted by fluorine, chlorine, hydroxyl, amino, C₁-C₆-alkyl, C₂-C₆- Alkenyl, C₂-C₆ alkynyl, C₁-C₆ acyloxy, benzoyloxy, C₁-C₆ alkoxy, C₁-C₆ alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted.

In a further preferred group of compounds of the formula I, Ia, Ib or Ic:
3) n zero, one, or two,
the individual substituents R 1 independently of one another are fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, hydroxy, mercapto, C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, amino, C 1 -C 4 -alkylamino, di (C 1 -C 4) alkylthio, C₄- alkyl) amino, (C₁-C₂-alkyl) oxycarbonyl (C₁-C₄-alkyl) amino, C₁-C₆ acyl, C₁-C₄ acylamino, or
a phenyl radical substituted by a radical R⁵,
where R⁵
Fluorine, chlorine, trifluoromethyl, C₁-C₄-alkyl, C₁-C₄-alkoxy may be,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X represents oxygen, sulfur or substituted nitrogen N-R², where R² may have the meanings given below.
Y is [R⁶], O-R⁶, S-R⁶, N-R⁶R⁷, N =CR⁶R⁷ or [C-R⁶R⁷R⁸], where R⁶, R⁷ and R⁸ may have the meanings given below,
R², R⁶, R⁷ and R⁸ may be identical or different and independently of one another hydrogen,
C₁-C₆-alkyl, optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₂-C₆ alkenyl optionally substituted with fluoro, chloro, cyano, amino, mercapto, hydroxy, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₃-C₆-alkynyl, optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₃-C₆cycloalkyl, optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄alkoxy, C₁-C₄alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, Phenylsulfdnyl, carboxy, carbamoyl;
C₅-C₆cycloalkenyl, optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄alkoxy, C₁-C₄alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
(C₃-C₆-cycloalkyl) - (C₁-C₂-alkyl), optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁ C₄-alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
(C₅-C₆cycloalkenyl) - (C₁-C₂-alkyl), optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁ C₄-alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₁-C₆-alkylcarbonyl, optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₂-C₆ alkenylcarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
(C₃-C₆-cycloalkyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
(C₅-C₆cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
(C₃-C₆-cycloalkyl) - (C₁-C₂-alkyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
(C₅-C₆cycloalkenyl) - (C₁-C₂-alkyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
C₁-C₆ alkyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl) amino, C₁-C₄ alkylthio;
C₂-C₆ alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, phenyl;
C₂-C₆ alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, phenyl;
C₁-C₆-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄alkoxy, phenyl;
C₂-C₆ alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, phenyl;
C₁-C₆-alkylamino and di (C₁-C₆-alkyl) aminocarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄-alkoxy, phenyl;
C₂-C₆ alkenylamino and di (C₁-C₆ alkenyl) aminocarbonyl optionally substituted by fluoro, chloro, C₁-C₄ alkoxy, phenyl;
C₁-C₆-alkylsulfonyl, optionally substituted by fluorine, chlorine, C₁-C₄alkoxy, phenyl;
C₂-C₆ alkenylsulfonyl;
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to three independent radicals R⁵, wherein the alkyl radical may each contain 1 to 4 carbon atoms and R⁵ is as defined above
or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R⁵, where the alkyl radical can contain in each case 1 to 3 C atoms, and
R³ and R⁴ are the same or different, independently of one another
C₁-C₆-alkyl, optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy, carbamoyl;
C₂-C₆ alkenyl optionally substituted with fluorine or chlorine, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfonyl, C₁-C₄ alkylsulfinyl;
C₃-C₆cycloalkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl;
C₃-C₆-cycloalkenyl, optionally substituted with fluorine or chlorine, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl;
or with up to three mutually independent radicals R⁵ substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, wherein the alkyl radical may each contain 1 to 3 carbon atoms and R⁵ is as defined above, one of R³ or R⁴ may be hydrogen.

R³ and R⁴ can work together too a radical linked via a double bond = C-Z¹Z², wherein Z¹ and Z² have the meaning given above for R³ and R⁴.

R³ and R⁴ or R³ and Y can also be used
Be part of a saturated or unsaturated carbocyclic or heterocyclic ring having 3 to 6 carbon atoms, optionally substituted by fluorine, chlorine, hydroxyl, amino, C₁-C₄-alkyl, C₂-C₄-alkenyl, C₂-C₄-alkynyl, C₁-C₄-alkenyl C₄-acyloxy, benzoyloxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted.

In a further preferred group of compounds of the formula I, Ia, Ib or Ic:
4) n zero, or one,
the individual substituents R¹ independently of one another fluorine, chlorine, trifluoromethyl, hydroxy, mercapto, C₁-C₃-alkyl, C₁-C₃-alkoxy, C₁-C₃-alkylthio, amino, C₁-C₃-alkylamino, di (C₁-C₃-alkyl) amino, (C₁-C₂-alkyl) oxycarbonyl (C₁-C₄-alkyl) amino, C₁-C₃-acylamino,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X represents oxygen, sulfur or substituted nitrogen N-R 2, where R 2 may have the meanings given below,
Y is O-R⁶, S-R⁶, N-R⁶R⁷ or N = CR⁶R⁷, where R⁶, R⁷ and R⁸ can have the meanings given below,
R₂, R₆, R₇ and R₈ are identical or different and independently of one another hydrogen,
C₁-C₆-alkyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₂-C₆ alkenyl optionally substituted with fluoro, chloro, amino, mercapto, hydroxy, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl ) amino, C₁-C₄-alkylthio;
C₃-C₈-alkynyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₃-C₆cycloalkyl, optionally substituted with fluorine, chlorine, C₁-C₄-acyloxy, benzoyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄-alkylthio ;
C₅-C₆-cycloalkenyl,
(C₃-C₆ cycloalkyl) - (C₁-C₂ alkyl),
(C₅-C₆-cycloalkenyl) - (C₁-C₂ alkyl),
C₁-C₆-alkylcarbonyl, optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₂-C₄-alkenylcarbonyl,
(C₃-C₆ cycloalkyl) carbonyl,
(C₅-C₆-cycloalkenyl) carbonyl,
(C₃-C₆ cycloalkyl) - (C₁-C₂-alkyl) carbonyl,
(C₅-C₆-cycloalkenyl) - (C₁-C₂-alkyl) carbonyl,
C₁-C₆ alkyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl) amino, C₁-C₄ alkylthio;
C₂-C₆ alkenyloxycarbonyl,
C₂-C₆ Alkynyloxycarbonyl,
C₁-Alkylthiocarbonyl,
C₂-C₆ Alkenylthiocarbonyl,
C₁-C₆-alkylamino and di (C₁-C₆-alkyl) aminocarbonyl,
C₂-C₆ alkenylamino and di (C₁-C₄ alkenyl) aminocarbonyl,
C₁-alkylsulfonyl,
C₂-C₆ Alkenylsulfonyl,
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to two independent radicals R⁵, wherein the alkyl radical may each contain 1 to 3 carbon atoms and R⁵ is as defined above under 3
or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to two mutually independent radicals R⁵, where the alkyl radical can contain in each case 1 to 2 C atoms, and
R₃ and R₄ are the same or different, independently of one another
C₁-C₆-alkyl, optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy,
C₂-C₆ alkenyl, optionally substituted with fluorine or chlorine,
C₃-C₆ cycloalkyl,
C₅-C₆cycloalkenyl optionally substituted with fluoro or chloro;
or aryl, arylalkyl, heteroaryl or heteroarylalkyl substituted with up to three independent radicals R⁵, where the alkyl radical can contain in each case 1 to 2 C atoms and R⁵ is as defined above,
one of R³ or R⁴ may be hydrogen,
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring having 3 to 6 carbon atoms, optionally substituted by fluorine, chlorine, hydroxyl, amino, C₁-C₄-alkyl, C₂-C₄- Alkenyl, C₂-C₄-alkynyl, C₁-C₄-acyloxy, benzoyloxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted.

In a very particularly preferred group of compounds of the formula I, Ia, Ib or Ic:
5) n zero
T, U, V and W are CH or N, with one nitrogen atom in the ring,
X represents oxygen, sulfur or substituted nitrogen N-R 2, where R 2 may have the meanings given below,
Y is O-R⁶, N-R⁶R⁷ or N = CR⁶R⁷, where R⁶ and the meanings given below may have.

R², R⁶ and R⁷ are the same or different, independently of one another
Hydrogen,
C₁-C₆-alkyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₂-C₆ alkenyl optionally substituted with fluoro, chloro, amino, mercapto, hydroxy, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl ) amino, C₁-C₄-alkylthio;
C₃-C₈-alkynyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₃-C₆cycloalkyl, optionally substituted by fluorine, chlorine, C₁-C₄-acyloxy, benzoyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄-alkylthio ;
C₅-C₆-cycloalkenyl,
(C₃-C₆ cycloalkyl) - (C₁-C₂ alkyl),
(C₅-C₆-cycloalkenyl) - (C₁-C₂ alkyl),
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, aryloxycarbonyl, substituted with up to two independent radicals R₅ where the alkyl radical can contain in each case 1 to 3 C atoms and R⁵ denotes chlorine, trifluoromethyl, C₁-C₄-alkyl or C₁-C₄-alkoxy,
R³ and R⁴ are the same or different, independently of one another
C₁-C₆-alkyl, optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy,
one of R³ or R⁴ may be hydrogen,
R³ and R⁴ or R³ and Y may also be part of a saturated or unsaturated carbocyclic ring having 3 to 6 carbon atoms, optionally substituted by fluorine, chlorine, hydroxy, amino, C₁-C₄alkyl, C₂-C₄alkenyl, C₂ C₄-alkynyl, C₁-C₄-acyloxy, benzoyloxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted.

Particularly preferred basic bodies of the abovementioned compounds of the formulas I or Ia, Ib and Ic are
1,5-diaza-naphthalene-2,4 (1H, 3H) -dione
1,6-diaza-naphthalene-2,4 (1H, 3H) -dione
1,7-diaza-naphthalene-2,4 (1H, 3H) -dione
1,8-diaza-naphthalene-2,4 (1H, 3H) -dione
1,5-diaza-naphthalen-4 (3H) -thione -one-2 (1H)
1,6-diaza-naphthalen-4 (3H) -thione -one-2 (1H)
Diaza-naphthalen-4-1,7 (3H) -thione -one-2 (1H)
1,8-diaza-naphthalen-4 (3H) -thione -one-2 (1H)

The alkyl groups mentioned in the preceding definitions can straight-chain or branched. Unless otherwise defined, included they are preferably 1 to 8, particularly preferably 1 to 6, in particular 1 to 4 C-atoms. Examples are the methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl and the like.

The alkenyl groups mentioned in the preceding definitions can straight chain or branched and contain 1 to 3 double bonds. Provided not otherwise defined, these groups preferably contain 2 to 8, in particular 2 to 6 C atoms. Examples are the 2-propenyl, 1-methylethenyl, 2-butenyl, 3-butenyl, 2-methyl-2-propenyl, 3-methyl-2-butenyl, 2,3-dimethyl 2-butenyl, 3,3-dichloro-2-propenyl and pentadienyl and the like.

The alkynyl groups mentioned in the preceding definitions can straight chain or branched and contain 1 to 3 triple bonds. Provided not otherwise defined, they preferably contain from 2 to 8, more preferably 3 to 6 C atoms. Examples are the 2-propynyl and 3-butynyl group and similar.  

The cycloalkyl and cycloalkyl groups mentioned in the preceding definitions Cycloalkenyl groups, unless otherwise defined, preferably 3 to 8, more preferably 4 to 6 C atoms. Examples are the cyclopropyl, Cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl or Cyclohexenyl.

The acyl groups mentioned in the preceding definitions can aliphatic, cycloaliphatic or aromatic. Unless otherwise defined, they preferably contain 1 to 8, more preferably 2 to 7 carbon atoms. Exemplary acyl groups are the formyl, acetyl, chloroacetyl, trifluoroacetyl, Hydroxyacetyl, glycyl, propionyl, butyryl, isobutyryl, pivaloyl, Cyclohexanoyl or benzoyl group.

For the aryl groups mentioned in the preceding definitions preferably aromatic groups having 6 to 14 carbon atoms, in particular with 6 to 10 carbon atoms such as phenyl and naphthyl.

In the above-mentioned heterocyclic rings or heteroaryl groups come as heteroatoms in particular for example O, S, N into consideration, wherein in the case of an N-containing ring N-Z saturated at this point, wherein Z, H or R² means the respective definitions described above. Unless otherwise defined, the heterocyclic rings are preferably 1 to 15 C atoms and 1 to 6 heteroatoms, in particular 3 to 11 C atoms and 1 to 4 heteroatoms.

For the heterocyclic rings mentioned in the preceding definitions or heteroaryl groups are, for example, thiophene, furan, pyridine, Pyrimidine, indole, quinoline, isoquinoline, oxazole, isoxazole, thiazole or isothiazole in Question.  

The aralkyl groups listed in the preceding definitions are for example, benzyl, phenylethyl, naphthylmethyl or styryl.

The abovementioned substituents R¹ to R⁸ are preferably 3-fold, particularly preferably 2-fold, in particular simply with the respectively indicated Substituents substituted.

For the respective constituent substituent definitions (such as Arylalkoxycarbonyl) are the previously described as preferred ranges for the individual substituents are also preferred.

Depending on the various substituents, compounds of the Formulas I, Ia, Ib and Ic have several asymmetric carbon atoms. The invention therefore provides both the pure stereoisomers also mixtures thereof, such as. B. the associated racemate.

The pure stereoisomers of the compounds of the formulas I, Ia, Ib and Ic leave itself by known methods or in analogy to known methods directly manufacture or subsequently separate.

The subject of the present invention further includes a method for Preparation of compounds of the formulas I, Ia, Ib and Ic as described above under 1) -5) explained, characterized in that

• A) for the preparation of compounds of the formulas I, Ib with X equal to oxygen and Ia, Ic with X as defined under 1) -5) with the exception of N-R² is NHY equal to R⁶, O-R⁶, S-R⁶, N -R⁶R⁷, NC-R⁶R⁷ or C-R⁶R⁷R⁸ and the radicals R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ as under 1) -5) defines a compound of formula II, IIa, IIb or IIc wherein for R¹, R², R³, R⁴ and R⁵ are the definitions mentioned under 1) -4), with a compound of formula III, Y-NH₂ (III) wherein Y is R⁶, O-R⁶, S-R⁶, N-R⁶R⁷ , N = C-R⁶R⁷ or C-R⁶R⁷R⁸ can mean and for R⁶, R⁷ and R⁸ the definitions mentioned under 1) -4) apply, is implemented or that
• B) Compounds of the formulas I, Ia, Ib and Ic with X, Y and the radicals R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ as defined under 1) -5) are prepared by Reaction of a compound of formula I, Ia, Ib or Ic, wherein for X and the Radicals R¹, R², R³, R⁴, R⁵ and R⁶ are the definitions mentioned under 1) -5) and Y is H, OH, SH, NH₂ or NHR⁶, with a reagent of formula IV, R⁹-Z (IV) where R⁹ is the meanings mentioned above under 1) -5) for R², R⁶, R⁷ and R⁸ except for hydrogen and Z is a leaving group or that
• C) Compounds of the formulas I and Ib, where X is sulfur and R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ as defined under 1) -5) are produced by Reaction of a compound of the formula I or Ib, wherein X is oxygen and for R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ mentioned under 1) -5) Definitions apply with a sulfurization reagent or that
• D) for the preparation of compounds of formulas I, Ia, Ib and Ic, with X and R¹, R², R³, R⁴ and R⁵ as defined under 1) -5) and Y is O-R⁶, S-R⁶ or N-R⁶R⁷ Compounds of the formulas I, Ia, Ib or Ic with X and R¹, R², R³, R⁴ and R⁵ as defined under 1) -5) and Y is OH, SH, NH₂ or NHR⁶ with a compound of the formula V, R⁹- OH (V) where R⁹
  Alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Cycloalkyl optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  (Cycloalkyl) - (alkyl), optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl,
  (Cycloalkenyl) - (alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl,
  Alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkyl) - (alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkenyl) - (alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, alkoxy, oxo, phenyl,
  or with up to five mutually independent radicals R⁵ substituted aryl, arylcarbonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, wherein R⁵ is as defined above
  or with up to three independent radicals R⁵ can be substituted heteroaryl, heteroarylalkyl, heteroarylalkenyl, Heteroarylalkylcarbonyl or Heteroarylalkenylcarbonyl
  be reacted in the presence of a dehydrating agent or that
• E) compounds of the formulas I and Ib where X is oxygen and Y, R¹, R², R³, R⁴ and R⁵ are as defined under 1) -4), by cyclization of a compound of the formula VI, with Y, R¹, R², R³, R⁴ and R⁵ as defined under 1) -5) and Z is a leaving group are prepared

The above-mentioned method A preferably proceeds as follows Conditions from:

The reaction is conveniently carried out in a solvent. Suitable z. As aromatic hydrocarbons such as toluene or xylene, Water, lower alcohols such as methanol, ethanol, methyl glycol or 1-butanol, Ethers such as tetrahydrofuran or glycol dimethyl ether, basic solvents such as Pyridine or N-methylimidazole, carboxylic acids such as acetic acid or mixtures this solvent.

The presence of a suitable acidic or basic catalyst z. B. p-toluenesulfonic acid, acetic acid, mineral acids or salts such as sodium acetate, Sodium carbonate, potassium carbonate or pyridinium hydrochloride is favorable. The reaction temperature may be between 0 and 200 ° C, preferably at the boiling temperature of the solvent.

The above-mentioned method B preferably proceeds as follows Conditions:

The substituent Z in the formula IV is a suitable leaving group, such as. B. Chlorine, bromine or iodine, a suitable radical of sulfuric acid aliphatic or aromatic sulfonic acid ester or optionally halogenated Acyloxy.

The reaction is conveniently carried out in a solvent in the presence a suitable base for capturing the acid liberated in the reaction carried out.

As solvents can be used aromatic hydrocarbons such as toluene or xylene, lower alcohols such as methanol, ethanol, methyl glycol or 1-butanol, ethers such as tetrahydrofuran or glycol dimethyl ether, dipolar  aprotic solvents such as N, N-dimethylformamide, N-methylpyrolidone, Acetonitrile, nitrobenzene, dimethylsulfoxide or mixtures of these solvents. Suitable bases are, for. B. alkali or alkaline earth metal carbonates or hydrogencarbonates such as sodium bicarbonate, sodium carbonate or Calcium carbonate, alkali or alkaline earth metal hydroxides such as potassium hydroxide or Barium hydroxide, alcoholates such as sodium ethoxide or potassium tert-butoxide, organolithium compounds such as butyllithium or lithium diisopropylamide, Alkali or alkaline earth metal hydrides such as sodium hydride or calcium hydride, Alkali metal fluorides such as potassium fluoride or an organic base such as Triethylamine or pyridine.

Also two-phase systems with aqueous solutions of bases in the presence a phase transfer catalyst such as. Benzyltriethylammonium chloride possible.

In some cases, the addition of an iodine salt, z. As lithium iodide attached.

The reaction usually takes place at temperatures between -10 and 160 ° C carried out, preferably at room temperature or the boiling point of the Solvent.

For this implementation, any nucleophilic substituents such. B. Hydroxy, mercapto or amino groups before carrying out the reaction in suitable derivatized or with splittable common Protecting groups such. As acetyl or benzyl, provided.

For the reaction as described above under C) is preferably as Sulfurization reagent 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane 2,4-disulfide (Lawesson's reagent), bis (tricyclohexyltin) sulfide, bis (tri-n-butyl) butyltin) sulfide, bis (triphenyltin) sulfide, bis (trimethylsilyl) sulfide or Phosphorus pentasulfide used. The reaction is conveniently carried out in one organic solvent or a solvent mixture, at Room temperature or higher, preferably at the boiling point of the Reaction mixture and if possible under anhydrous conditions  carried out. Suitable z. As carbon disulphide, toluene, xylene, pyridine or 1,2-dichloroethane. When using the mentioned tin or Silylsulfide is it is appropriate to use the sulfurization reaction in the presence of a Lewis acid Boron trichloride perform.

In the presence of other carbonyl groups, these are optionally before Sulfurization reaction by known methods by a suitable Protecting group, e.g. As by acetalization to protect.

For the reaction described above under D) dehydrating Systems such as Dialkylazodicarbonsäureester and Trialkyl- or Triarylphosphin needed (Mitsunubo).

Suitable solvents for this reaction are halogenated solvents such as Dichloromethane or 1,2-dichloroethane, ethers such as tetrahydrofuran or 1,2-dimethoxyethane, aromatic hydrocarbons such as toluene or xylene or mixtures of these solvents.

It should be worked under anhydrous conditions.

The reaction is preferably carried out at temperatures between 0 and 100 ° C, particularly preferably carried out at room temperature.

The cyclization described under E) takes place in a suitable solvent like lower alcohols, eg. For example, methanol, ethanol or methyl glycol, ethers, z. B. Tetrahydrofuran or 1,2-dimethoxyethane, dipolar aprotic solvents, z. N, N-dimethylformamide or N-methylpyrolidone in the presence of a base; suitable are alkali metal or alkaline earth metal carbonates or bicarbonates such as Sodium carbonate, calcium carbonate or sodium bicarbonate, alkali or Alkaline earth metal hydroxides such as potassium hydroxide or barium hydroxide, alkoxides such as sodium ethoxide or potassium tert-butoxide, organolithium compounds such as butyllithium or lithium diisopropylamide, alkali or Erdalkalihydride as Sodium hydride or calcium hydride or an organic base such as triethylamine or pyridine - the latter can also be used as a solvent, or organic or inorganic acids such as acetic acid, trifluoroacetic acid,  Hydrochloric acid or phosphoric acid.

The reaction is preferably carried out at temperatures between -10 and 120 ° C, particularly preferably carried out at room temperature.

The substituent Z in the formula VI is hydroxy, alkoxy, chlorine, bromine or Iodine or optionally halogenated acyloxy.

The starting materials of the general formulas II, IIa, IIb or IIc are known from the literature or can be described by literature methods produce. The synthesis is z. B. of Azaisatosäureanhydriden from the formula VII, which with compounds of formula VIIa to the derivatives of the general Formula II, IIa, IIb or IIc are reacted (see U.S. Patent 3,887,550 (1975), U.S. Pat. 3,947,416 (1976), G.M. Coppola et al., J. Heterocyclic Chemistry 22, 193 (1985) and G.M. Coppola, Synthesis 1980, 505 and cited therein Literature). M represents in formula VIIa the metal atom or a Metal atom equivalent, preferably an alkaline earth or alkali metal, preferably lithium.

The medicaments of the invention may be enteral (oral), parenteral (intravenously), rectally, subcutaneously, intramuscularly or locally (topically) become.  

They can be in the form of solutions, powders (tablets, capsules including Microcapsules), ointments (creams or gels) or suppositories become. As adjuvants for such formulations come the pharmaceutically customary liquid or solid fillers and extenders, Solvents, emulsifiers, lubricants, flavoring agents, dyes and / or buffer substances in question.

As appropriate dosage are 0.1 to 10, preferably 0.2 to 8 mg / kg Body weight administered one or more times a day. The used Dosage units are expediently based on the respective Pharmacokinetics of the substance used or used galenic Preparation.

The dosage unit used of the compounds according to the invention is z. 1 to 1500 mg, preferably 50 to 500 mg.

The compounds of the invention may also be used in combination with others antiviral agents, such as. Nucleoside analogs, protease inhibitors, other RT Inhibitors or adsorption inhibitors and immunostimulants, interferons, Interleukins and colony stimulating factors (eg GM-CSF, G-CSF, M-CSF).

efficacy tests Testing of preparations against HIV in cell culture methods Description medium RMPI pH 6.8

Complete medium also contains 20% fetal calf serum and 40 IU / ml recombinant interleukin 2.  

cell

Isolated from fresh donor blood by Ficol® gradient centrifugation Lymphocytes are supplemented with 2 g / ml of phytohemagglutinin (Wellcome) in complete medium for 36 h at 37 ° C under 5% CO2. The cells after addition of 10% DMSO at a cell density of 5 × 10⁶ frozen and stored in liquid nitrogen. For the experiment, the Thawed cells, washed in RPMI medium and in complete medium 3 to Cultivated for 4 days.

approach

The investigational medicinal products were in a concentration of 16.7 mg / ml in DMSO dissolved and diluted in complete medium to 1 mg / ml.

In 24-well multiwell dishes 0.4 ml of medium were submitted. After adding 0.1 ml of dissolved drug in the top row of a dish was passed through Transfer each 0.1 ml generated a geometric dilution series. Specimen-free controls always contained 0.4 ml of complete medium at 0.5% DMSO.

Lymphocyte cultures with a cell count of 5 × 10⁵ cells / ml were performed Add 1/50 volume supernatant from HIV-infected lymphocyte cultures infected. The titer of these culture supernatants was by end point dilution with 1 to 5 x 10⁶ infectious units / ml. After incubation for 30 min 37 ° C, the infected lymphocytes were centrifuged off and in the same Volume medium resumed. From this cell suspension were add 0.6 ml to all wells of the test plate. The approaches were Incubated for 3 days at 37 ° C.

evaluation

The infected cell cultures were examined under the microscope for the presence of Examined giant cells indicating an active virus multiplication in culture. The lowest drug concentration at which no giant cells occurred was determined as an inhibitory concentration against HIV. As a control, the Supernatants from the culture plates using an HIV antigen test accordingly  the manufacturer's instructions (Organon) for the presence of HIV antigen certainly.

Results

The results of this test are shown in Table 1.

Table 1

Examination of the substances for inhibition of HIV "reverse transcriptase"

The activity of the reverse transcriptase (RT) was determined by means of a "Scintillation Proximity Assay "(SPA).

Reagent kit for the RT-SPA was purchased from Amersham / Buchler (Braunschweig) based. The enzyme RT (cloned from HIV into E. coli) originated from the company HT- Biotechnology LTD, Cambridge, UK.  

approach

The test was carried out according to the method manual of the manufacturer Amersham carried out - with the following modifications:

• bovine serum albumin became the final concentration in the "assay" buffer 0.5 mg / ml added.
• The test was carried out in Eppendorf reaction vessels with 100 ml Batch volume performed.
• The manufacturer's RT concentrate (5000 U / ml) was buffered in Tris-HCl 20 mM; pH 7.2; 30% glycerol diluted to an activity of 1 5 U / ml.
• the incubation time for the batches was 60 min (37 ° C).
• - after stopping the reaction and "developing" with the pearl Suspension, 130 ml batch in 4.5 ml Tris-HCl buffer, 10 mM; pH 7.4; Transferred 0.15 M NaCl and the tritium activity in a β-counter measured.

substance testing

For a preliminary assay of inhibitor activity, the substances were dissolved in DMSO (stock solution c = 1 mg / ml) and tested in dilution in DMSO 10 ^-1 , 10 ^-2 , 10 ^-3 , etc.

For the determination of IC₅₀ values, the inhibitor stock solutions in Tris HCl buffer, 50 mM, pH 8 further diluted and in appropriate concentrations tested.

From the plot of RT activity versus Log C _Inh. , The concentration associated with a 50% enzyme inhibition was determined.

The results of the study are shown in Table 2.

Connection of the no. Reverse transcriptase assay IC₅₀ (mcg / ml) 2 0.1-1 3 0.1 4 0.2 5 1-10 6 0.1-1 11 0.1-1 13 0.01-0.1

By the following examples as well as by the content of the claims the present invention will be explained in more detail.

example 1 Preparation of 3,3-dimethyl-1,8-diazanaphthalene-2,4 (1H, 3H) -dione (1)

By reaction of 100 mmol diisopropylamine in 50 ml absolute Tetrahydrofuran with 100 mmol of 1.6 molar n-butyl lithium solution in n-hexane at -78 ° C a lithium diisopropyl amide solution is herges 17295 00070 552 001000280000000200012000285911718400040 0002004344452 00004 17176tellt.

At a temperature of -78 ° C, 5.4 ml (40 mmol) are added to this solution Isobuttersäureethylester added dropwise over 30 minutes. The Reaction mixture is 30 minutes at 0 ° C after completion of the addition stirred. Subsequently, this solution is at -30 ° C within 30 minutes to a suspension of 6.0 g (37 mmol)  8-Azaisatosäureanhydrid added dropwise in 20 ml of absolute tetrahydrofuran. To Completion of the addition is stirred at 25 ° C for 6 hours.

For workup, the reaction mixture is added to 100 ml of ice water and acidified with conc. Hydrochloric acid acidified. Then it is extracted three times with 100 ml of ethyl acetate and the combined organic phases are washed several times with a little water. After drying the organic phase using Na₂SO₄ is concentrated on a rotary evaporator under reduced pressure. The crude product obtained in this way is recrystallized from MTB ether / n-heptane (1: 1).
Yield: 2.41 g (colorless crystals, melting point: 210-211 ° C) 35% of theory
MS spectrum: MS: (M + H) + = 191
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.33 (6H, s), 7.18 (1H, dd), 8.13 (1H, dd), 8.54 (1H, dd), 11.19 (br s, 1H)

Example 2 Preparation of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-oxime (8)

1.4 g (7.4 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione are dissolved in Dissolve 20 ml of absolute pyridine and add 2.1 g (4 equivalents) Hydroxylamine hydrochloride added. The reaction mixture is allowed to stand for 5 hours stirred at a temperature of 90 ° C.

For workup is concentrated on a rotary evaporator under reduced pressure and the remaining oily residue taken up in ethyl acetate. It is then washed once with 1 N aqueous hydrochloric acid and several times with water. After drying the organic phase using Na₂SO₄ and distilling off the solvent results in an oily residue, which is purified by column chromatography on silica gel (eluent ethyl acetate:
n-heptane = 1: 1) is purified. The reaction product is obtained in the form of yellowish crystals.
Yield: 0.82 g (54%)
Melting point: 253-256 ° C
MS spectrum: MS: (M + H) ⁺ = 206
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.20 (s, 6H), 7.11 (dd, 1H), 8.28 (dd, 1H), 8.65 (dd, 1H), 10.8 (br s, 1H), 11.82 (br s, 1H)

Example 3 Preparation of 3,3-dimethyl-1-n-propyl-1,8-naphyridine-2,4 (1H, 3H) -dione-4-O- n-propyl oxime (9) and 3,3-dimethyl-1,8-naphthyrin-2,4 (1H, 3H) -dione-4-O-n- propyl oxime (12)

0.5 g (2.44 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-oxime are dissolved in 15 ml of absolute tetrahydrofuran and with 3 ml of n-propanol added. At a temperature of -15 ° C, 1.92 g (3 equivalents) Triphenylphosphine added. Then 1.5 ml (4 equivalents) Diethyl azodicarboxylate added dropwise in 3 ml of n-propanol and the temperature kept at -5 ° C by cooling. After completion of the addition is still 1 Stirred hour at -5 ° C.

For working up the reaction mixture is concentrated in vacuo and the purified crude product purified over silica gel (mobile phase: Ethyl acetate / n-heptane = 1/3). After removal of the solvent you get two fractions as reaction products. In the less polar fraction 1 is 3,3-dimethyl-1-n-propyl-1,8-naphthyridine-2,4 (1H, 3H) -dione 4-O-n-propyl oxime, in the second fraction 3,3-dimethyl-1,8-naphthyridine 2,4 (1H, 3H) -dione-4-O-n-propyl-oxime.

Fraction 1 (3,3-Dimethyl-1-n-propyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-n-prop-yl oxime, (9)

Yield: 0.45 g (64 d of th.), Colorless oil (R _F

Value: 0.65; mobile phase: ethyl acetate / n-heptane = 1/3)
MS spectrum: MS: (M + H) ⁺ = 290
1H NMR (200 MHz, d₆-DMSO):
δ = 0.88 (t, 3H), 0.90 (t, 3H), 1.30 (s, 6H), 1.75-1.50 (2m, 4H), 4.22-4.00 (2t, 4H), 7.22 (dd, 1H), 8.45 ( dd, 1H) 8.55 (dd, 1H)

Fraction 2 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-n-propyl-oxime, (12)

Yield: 0.12 g (20%), colorless crystals of melting point 98-99 ° C (R _F value: 0.36, mobile phase: ethyl acetate / n-heptane = 1/3).
MS spectrum: MS: (M + H) ⁺ = 248
1 H NMR (200 MHz, d₆-DMSO):
6 = 1.90 (t, 3H), 1.30 (s, 6H), 1.65 (dt, 2H), 4.08 (t, 2H), 7.15 (dd, 1H), 8.30 (dd, 1H), 8.54 (dd, 1H) , 10.90 (br s, 1H)

Example 4 Preparation of 3,3-dimethyl-1,8-naphthyridin-4 (3H) -one-2 (1H) -thione-4-O-n- propyl oxime (11)

62 mg (0.25 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-n- propyl oxime (Example 3) are dissolved in 10 ml abs. Toluene and dissolved with 60 mg (0.1 5 mmol) Lawesson's reagent (2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4- diphosphetane-2,4-disulfide). The reaction mixture is allowed to stand for 8 hours 100 ° C stirred.  

For workup, the crude product is concentrated on a rotary evaporator under reduced pressure and the remaining oily residue purified by column chromatography on silica gel (mobile phase: ethyl acetate / n-heptane = 1/3). After distilling off the mobile phase results in a pale yellow oil, which crystallized after addition of n-heptane / MTB ether.
Yield: 20 mg (30% of theory), mp 140-142 ° C., (R _F value: 0.69, mobile phase: ethyl acetate / n-heptane = 1/2)
MS spectrum: MS: (M + H) ⁺ = 263

Example 5 Preparation of 3,3-dimethyl-1,8-naphthyridin-4 (3H) -one-2 (1H) -thione-4-oxime (14)

200 mg (0.976 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-oxime (Example 2) are dissolved in 30 ml of abs. Toluene and dissolved with 220 mg (0.586 mmol) Lawesson's reagent (2,4-bis- (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane 2,4-disulfide). The reaction mixture is at 100 ° C for 6 hours touched.

For workup, the crude product was concentrated on a rotary evaporator under reduced pressure and the remaining oily residue was purified by column chromatography on silica gel (mobile phase: ethyl acetate / n-heptane = 1/2). After distilling off the mobile phase results in a pale yellow oil, which crystallized after addition of n-heptane / MTB ether.
Yield: 20 mg (9% of theory), melting point 200-205 ° C., (R _F value: 0.29, mobile phase: ethyl acetate / n-heptane = 1/1)
MS spectrum: MS: (M + H) ⁺ = 222

Example 6 Preparation of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-ethyl oxime (5)

0.5 g (2.6 mmol) of 3,3-dimethyl-1,8-diazanaphthalene-2,4 (1H, 3H) -dione (Experiment 1) are dissolved in 10 ml of absolute pyridine and 200 mg (1.5 equivalents) of O-ethylhydroxylamine Hydrochloride). The reaction mixture is heated to 90 ° C for 3 hours. After renewed addition of 200 mg of O-ethylhydroxylamine hydrochloride is heated to 90 ° C for a further 3 hours. For workup is concentrated on a rotary evaporator under reduced pressure and the oily residue triturated with 96% ethanol. For further purification is recrystallized from 96% ethanol.
Yield: 0.35 g (58% of theory), colorless crystals of melting point 110-112 ° C., (R _F value: 0.62, mobile phase: ethyl acetate / n-heptane = 1/1)
MS spectrum: MS: (M + H) ⁺ = 234
1H NMR (200 MHz, d₆-DMSO):
δ = 1.25 (t, 3H), 1.30 (s, 6H), 4.15 (q, 2H), 7.13 (dd, 1H), 8.28 (dd, 1H) 8.28 (dd, 1H), 8.55 (dd, 1H), 10.90 (br s, 1H)

Example 7 Preparation of 3,3-dimethyl-1,8-naphthyridin-4 (3H) -one-2 (1H) -thione-4-O-ethyloxime (2)

200 mg (0.858 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-ethyloxime (Experiment 6) are dissolved in 10 ml of absolute toluene and mixed with 210 mg (0.515 mmol) Lawesson's reagent (2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2,4-disulfide) - added. The reaction mixture is stirred for 5 hours at 100.degree.

For working up, the mixture is concentrated under reduced pressure and the remaining residue is chromatographed on silica gel (mobile phase: ethyl acetate / n-heptane = 1/3). The oil remaining after chromatography crystallizes after addition of a little n-heptane.
Yield: 90 mg (42 d.s.), pale yellow crystals, (RFT value: 0.65, mobile phase: ethyl acetate / n-heptane = 1/2).
MS spectrum: MS: (M + H) ⁺ = 250
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.24 (t, 3H), 1.41 (s, 6H), 4.18 (q, 2H), 7.26 (dd, 1H), 8.42 (dd, 1H), 8.55 (dd, 1H), 12.72 (br s, 1H )

Example 8 Preparation of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-isopropyloxime (6)

A solution of 0.38 g (1.63 mmol) of 3,3-dimethyl-1,8-diazanaphthalene-2,4 (1H, 3H) -dione in 10 ml of absolute pyridine is mixed with 0.86 g (4 equivalents) of O-iso-propylhydroxylamine Hydrochloride and the reaction mixture was stirred at 100 ° C for 4 hours.

After distilling off the solvent on a rotary evaporator under reduced pressure, the oily residue is brought to trituration by trituration with the addition of isopropanol.
Yield: 210 mg (52% of theory), colorless crystals of melting point 120-123 ° C. (R _F value: 0.31, mobile phase: ethyl acetate / n-heptane = 1/2)
MS spectrum: MS: (M + H) ⁺ = 248

Example 9 Preparation of 3,3-dimethyl-1,8-naphthyridine-4 (3) -one-2 (1H) -thione-4-O-isopropyl oxime (3)

110 mg (0.445 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-isopropyloxime are dissolved in 10 ml of absolute toluene and 100 mg (0.27 mmol) of Lawesson's  Reagent (2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2,4-disulfide) - added. The reaction mixture is stirred for 8 hours at 90.degree. After addition of another 50 mg Lawesson's reagent is stirred again at 90 ° C for 3 hours.

For workup, the reaction mixture is concentrated on a rotary evaporator under reduced pressure, the crude product obtained in this way is purified by chromatography on silica gel (mobile phase: MTB ether / n-heptane = 1/1) and then recrystallized from n-heptane.
Yield: 60 mg (51% of theory), colorless crystals of melting point 152-54 ° C. (R _F value: 0.72, mobile phase: MTB ether / n-heptane = 1/1)
MS spectrum: MS: (M + H) ⁺ = 264
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.24 (d, 6H), 1.43 (s, 6H), 4.38 (hept., 1H), 7.28 (dd, 1H), 8.40 (dd, 1H), 8.58 (dd, 1H), 12.71 (br s, 1H)

Example 10 Preparation of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-methyloxime (7)

A solution of 1 g (5.3 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione in 15 ml of absolute pyridine is treated with 1.76 g (21.2 mmol) of O-methylhydroxylamine hydrochloride and the mixture was stirred at 90 ° C for 3 hours.

For workup, the solvent is removed on a rotary evaporator under reduced pressure. The oily residue is taken up in ethyl acetate and the organic phase is extracted once by shaking with 2N aqueous hydrochloric acid solution and 3 times saturated aqueous sodium chloride solution. After drying the organic phase over Na₂SO₄ and removing the solvent on a rotary evaporator gives an oily residue, which crystallized after the addition of a little MTB ether.
Yield: 0.54 g (47% of theory), colorless crystals of melting point 154-156 ° C. (R _F value: 0.42, mobile phase: ethyl acetate / n-heptane = 1/2)
MS spectrum: MS: (M + H) ⁺ = 220
1H-NMR spectrum is a syn / anti-diastereomer mixture (61: 39) Main component:
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.30 (s, 6H), 3.78 (s, 3H), 7.13 (dd, 1H), 8.32 (dd, 1H), 8.53 (dd, 1H), 10.90 (br s, 1H)
Subcomponent:
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.61 (s, 6H), 3.93 (s, 3H), 7.05 (dd, 1H), 8.16 (dd, 1H) (8.29 (dd, 1H), 10.86 (br s, 1H)

Example 11 Preparation of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-2-oxime-4-O-n- methyloxime (10)

100 mg (0.426 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-methyloxime (Experiment 10) are dissolved in 10 ml of absolute ethanol and treated with 150 mg (5 equivalents) Hydroxylamine hydrochloride and with 0.28 ml (5 equivalents) of triethylamine. The reaction mixture is stirred for 3 hours at 90.degree.

For workup, the reaction solution is concentrated under reduced pressure on a rotary evaporator and the oily residue taken up with ethyl acetate. The organic phase is washed twice with water and dried over Na₂SO₄. After concentration of the organic phase remains a pale yellow oil, which crystallized after addition of MTB ether / n-heptane.
Yield: 100 mg (quantitative), colorless crystals of melting point 202-204 ° C. (R _F value: 0.16, mobile phase: ethyl acetate / n-heptane = 1/3)
MS spectrum: MS: (M + H) ⁺ = 235
1 H NMR (200 MHz, d₆-DMSO):
δ = 1.28 (s, 6H), 3.88 (s, 3H), 6.95 (dd, 1H), 8.23 (dd, 1H), 8.41 (dd, 1H), 8.65 (br s, 1H), 10.38 (br s, 1H)

Example 12 Preparation of 3,3-dimethyl-1,8-naphthyridin-4 (3H) -one-2 (1H) -thione-4-O-methyloxime (4)

400 mg (1.8 mmol) of 3,3-dimethyl-1,8-naphthyridine-2,4 (1H, 3H) -dione-4-O-methyloxime (7) are dissolved in 20 ml of absolute toluene and mixed with 410 mg of Lawesson's reagent (2,4-bis). (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2,4-disulfide). The Reaction mixture is stirred at 80 ° C for 5 hours.

For workup, the reaction solution is then concentrated under reduced pressure on a rotary evaporator and the remaining residue is chromatographed on silica gel (mobile phase: ethyl acetate / n-heptane = 1/3). The residue obtained after the column chromatography and removal of the solvent crystallizes upon addition of n-heptane.
Yield: 290 mg (69% of theory), colorless crystals of melting point 173-174 ° C. (R _F value: 0.62, mobile phase: MTB ether / n-heptane = 1/2)
MS spectrum: MS: (M + H) ⁺ = 236
1H NMR (200 MHz, d₆-DMSO):
δ = 1.42 (s, 6H), 3.91 (s, 3H), 7.25 (dd, 1H), 8.43 (dd, 1H), 8.53 (dd, 1H), 12.78 (br s, 1H)

Example 13 Preparation of 3-cyclopentylidene-1,8-naphthyridine-2,4 (1H, 3H) -dione

By reaction of 13.6 ml (96 mmol) of diisopropylamine in 100 ml of absolute Tetrahydrofuran with 96 mmol of 1.6 molar n-butyl lithium solution in n-hexane at -78 ° C. a lithium diisopropylamide solution is prepared.

At a temperature of -60 ° C., 5.68 ml (40 mmol) of cyclopentylcarboxylic acid ethyl ester are added dropwise to this solution within 30 minutes. The reaction mixture is stirred for another 30 minutes at 0 ° C after completion of the addition. Subsequently, this solution is added dropwise at -30 ° C within 30 minutes to a suspension of 6.0 g (37 mmol) of 8-Azaisatosäureanhydrid in 40 ml of absolute tetrahydrofuran. After completion of the addition, the reaction mixture is stirred for 6 hours at 25 ° C. For workup is added to 100 ml of ice water and acidified with conc. Hydrochloric acid acidified. The mixture is then extracted three times with 100 ml of ethyl acetate and the combined organic phases are washed several times with a little water. After drying the organic phase using Na₂SO₄ is concentrated on a rotary evaporator under reduced pressure. The crude product obtained in this way is recrystallized from isopropanol.
Yield: 1.23 g (14%), colorless crystals of melting point 225 ° C. (R _F value: 0.63, mobile phase: ethyl acetate / n-heptane = 2/1)
MS spectrum: MS: (M + H) ⁺ = 217
1H NMR (200 MHz, d₆-DMSO):
δ = 1.60-1.82 (m, 4H), 1.96-2.15 (m, 4H), 7.18 (dd, 1H), 8.11 (dd, 1H), 8.53 (dd, 1H), 11.16 (br s, 1H)

Example 14 Preparation of Preparation of 3-Cyclopentylidene-1,8-naphthyridine-2,4 (1H, 3H) -dione-4 O-ethyloxime (13)

200 mg (0.93 mmol) of 3-cyclopentylidene-1,8-naphthyridine-2,4 (1H, 3H) -dione (see Experiment 13), dissolved in 20 ml of absolute pyridine, are mixed with 360 mg of Ethylhydroxylaminhydrochlorid added and the reaction mixture for 8 hours at a Temperature of 90 ° C stirred.

For workup, the reaction mixture is concentrated under reduced pressure on a rotary evaporator and taken up in 200 ml of ethyl acetate. The organic phase is washed once with 1 N aqueous hydrochloric acid and three times with water. After drying the organic phase using Na₂SO₄ is concentrated on a rotary evaporator and the crude product obtained by chromatography on silica gel (mobile phase: ethyl acetate / n-heptane = 1/1). The reaction product crystallized when distilling off the mobile phase on Rotationsver evaporator.
Yield: 40 mg (16% of theory), colorless crystals of melting point 110-112 ° C. (R _F value: 0.65, mobile phase: ethyl acetate / n-heptane = 2/1)
MS spectrum: MS: (M + H) ⁺ = 260

Claims (9)

1. Compounds of the formula I, and their tautomeric forms of general formula Ia, Ib and Ic, in which mean:
1) n zero, one, two or three,
the individual substituents R¹ independently of one another fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxy, mercapto, alkyl, cycloalkyl, alkoxy, alkoxy-alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, where the alkyl groups may be substituted by fluorine, chlorine , Hydroxy, amino, alkoxy, alkylamino, dialkylamino, acyloxy, acylamino, carboxy, aminocarbonyl, alkyloxycarbonyl;
Nitro, amino, azido, dialkylamino, piperidino, piperazino, N-methylpiperazino, morpholino, 1-pyrrolidinyl, acyl, acyloxy, acylamino, cyano, carbamoyl, carboxy, alkyloxycarbonyl, hydroxysulfonyl, sulfamoyl, or
a phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, heteroaroyl or heteroaryl radical which is unsubstituted or substituted by up to five independent radicals R⁵,
where R⁵
Fluoro, chloro, bromo, iodo, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, azido, alkyl, cycloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkyloxycarbonyl, phenyl, phenoxy or heteroaryl,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X is oxygen, sulfur, selenium or substituted nitrogen N-R², where R² may have the meanings given below,
Y is [R⁶], O-R⁶, S-R⁶, N-R⁶R⁷, N =C-R⁶R⁷ or [C-R⁶R⁷R⁸], where R⁶, R⁷ and R⁸ may have the meanings given below,
R², R⁶, R⁷ and R⁸ may be identical or different and independently of one another hydrogen,
Alkyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Alkenyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Alkynyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Cycloalkyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Cycloalkenyl optionally substituted with fluoro, chloro, bromo, iodo, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
(Cycloalkyl) - (alkyl), optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl;
(Cycloalkenyl) - (alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl;
Alkylcarbonyl optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
Alkenylcarbonyl optionally substituted by fluoro, chloro or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkyl) carbonyl optionally substituted by fluoro, chloro or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkyl) - (alkyl) carbonyl, optionally substituted by fluoro, chloro or hydroxy, alkoxy, oxo, phenyl;
(Cycloalkenyl) - (alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl;
Alkyloxycarbonyl optionally substituted by fluoro, chloro, bromo, hydroxy, alkoxy, alkylamino, dialkylamino, alkylthio;
Alkenyloxycarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkynyloxycarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkylthiocarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
Alkylamino and dialkylaminocarbonyl, optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkenylamino and dialkenylaminocarbonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
Alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxy, alkoxy, alkylthio, oxo, phenyl;
Alkenylsulfonyl optionally substituted by fluoro, chloro, hydroxy, alkoxy, oxo, phenyl;
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to five mutually independent radicals R⁵, wherein R⁵ is as defined above or substituted with up to three independent radicals R⁵ substituted heteroaryl, heteroarylalkyl, heteroarylalkenyl, Heteroarylalkylcarbonyl or Heteroarylalkenylcarbonyl, and
R³ and R⁴ are identical or different and independently of one another hydrogen,
Alkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
Alkenyl, optionally substituted by fluorine or chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
Cycloalkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
Cycloalkenyl optionally substituted with fluorine or chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl; or
with up to five mutually independent radicals R⁵ substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, where R⁵ is as defined above,
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring, optionally with fluorine, chlorine, hydroxyl, amino, alkyl, alkenyl, alkynyl, acyloxy, benzoyloxy, alkoxy, alkylthio, oxo, thioxo Carboxy, carbamoyl or phenyl may be substituted,
and their optical isomers, diastereomers in pure form or in the form of their mixtures and their addition salts and prodrugs. 2. Compounds of formula I, Ia, Ib or Ic according to claim 1, wherein mean
2) n zero, one, or two
the individual substituents R¹ independently
Fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, hydroxy, mercapto, C₁-C₆-alkyl, C₅-C₆-cycloalkyl, C₁-C₄-alkoxy, (C₁-C₄-alkoxy) - (C₁-C₂-alkoxy), C₁- C₄-alkylthio, C₁-C₄-alkylsulfinyl, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylamino, wherein the alkyl groups may be substituted with fluorine, chlorine, hydroxyl, amino, carboxy, aminocarbonyl, C₁-C₄-alkyloxycarbonyl;
Amino, di (C₁-C₄-alkyl) amino, C₁-C₄-acyl, C₁-C₄-acyloxy, C₁-C₄-acylamino, cyano, carbamoyl, carboxy, (C₁-C₄-alkyl) -oxycarbonyl or
a phenyl, phenoxy, benzoyl, heteroaroyl or heteroaryl radical substituted by a radical R⁵,
where R⁵
Fluorine, chlorine, trifluoromethyl, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₄-alkoxy, may be,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X is oxygen, sulfur, selenium or substituted nitrogen N-R², where R² may have the meanings given below,
Y is [R⁶], O-R⁶, S-R⁶, N-R⁶R⁷, N =CR⁶R⁷ or [C-R⁶R⁷R⁸], where R⁶, R⁷ and R⁸ may have the meanings given below,
R², R⁶, R⁷ and R⁸ may be identical or different and independently of one another hydrogen,
C₁-C₈-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₂-C₈ alkenyl, optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ alkoxy, C₁-C₆ alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₃-C₈-alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆-alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₃-C₈cycloalkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆alkoxy, C₁-C₆-alkylamino, Di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₅-C₈cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
(C₃-C₈cycloalkyl) - (C₁-C₄alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ Alkoxy, C₁-C₆alkylamino, di (C₁-C₆alkyl) amino, C₁-C₆alkylthio, C₁-C₆alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
(C₅-C₈cycloalkenyl) - (C₁-C₄-alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ Alkoxy, C₁-C₆alkylamino, di (C₁-C₆alkyl) amino, C₁-C₆alkylthio, C₁-C₆alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₁-C₆-alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₆-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₆ alkoxy, C₁-C₆-alkylamino, di (C₁-C₆-alkyl) amino, C₁-C₆-alkylthio, C₁-C₆-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₂-C₈ alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
(C₃-C₈cycloalkyl) carbonyl, optionally substituted by fluoro, chloro or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
(C₅-C₈cycloalkenyl) carbonyl optionally substituted by fluoro, chloro or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
(C₃-C₈cycloalkyl) - (C₁-C₃alkyl) carbonyl, optionally substituted by fluoro, chloro or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
(C₅-C₆cycloalkenyl) - (C₁-C₃alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, C₁-C₄alkoxy, oxo, phenyl;
C₁-C₈-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, bromine, hydroxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄-alkylthio;
C₂-C₈ alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₂-C₈ alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₁-C₈-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
C₂-C₈ alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₁-C₈-alkylamino and di (C₁-C₈-alkyl) aminocarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
C₂-C₈ alkenylamino and di (C₁-C₆ alkenyl) aminocarbonyl optionally substituted by fluoro, chloro, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
C₁-C₆-alkylsulfonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, phenyl;
C₂-C₆ alkenylsulfonyl optionally substituted by fluoro, chloro, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to three independent radicals R⁵, wherein the alkyl radical may each contain 1 to 5 carbon atoms and R⁵ is as defined above
or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R⁵, where the alkyl radical can contain in each case 1 to 3 C atoms, and
R³ and R⁴ are identical or different and independently of one another hydrogen,
C₁-C₈-alkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy,
C₁-C₄alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfinyl, carboxy, carbamoyl;
C₂-C₈ alkenyl optionally substituted with fluoro or chloro, hydroxy, amino, mercapto, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄alkylsulfinyl, carboxy, carbamoyl;
C₃-C₈cycloalkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl, carboxy, carbamoyl;
C₃-C₈-cycloalkenyl, optionally substituted by fluorine or chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄alkylsulfinyl, carboxy, carbamoyl;
with up to three mutually independent radicals R⁵ substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, wherein the alkyl radical may each contain 1 to 3 carbon atoms and R⁵ is as defined above,
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring having 3 to 8 carbon atoms, optionally substituted by fluorine, chlorine, hydroxyl, amino, C₁-C₆-alkyl, C₂- C₆- Alkenyl, C₂-C₆ alkynyl, C₁-C₆ acyloxy, benzoyloxy, C₁-C₆ alkoxy, C₁-C₆ alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted. 3. Compounds of the formula I, Ia, Ib or Ic, according to claims 1 or 2, wherein
3) n zero, one, or two,
the individual substituents R 1 independently of one another fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, hydroxy, mercapto, C₁-C₆-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio, amino, C₁-C₄-alkylamino, di (C₁-C Alkyl) alkylthio, C₄-alkyl) amino, (C₁-C₂-alkyl) oxycarbonyl (C₁-C₄-alkyl) amino, C₁-C₆-acyl, C₁-C₄-acylamino, or
a phenyl radical substituted by a radical R⁵,
where R⁵
Fluorine, chlorine, trifluoromethyl, C₁-C₄-alkyl, C₁-C₄-alkoxy may be,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X represents oxygen, sulfur or substituted nitrogen N-R², where R² may have the meanings given below.
Y is [R⁶], O-R⁶, S-R⁶, N-R⁶R⁷, N =CR⁶R⁷ or [C-R⁶R⁷R⁸], where R⁶, R⁷ and R⁸ may have the meanings given below,
R², R⁶, R⁷ and R⁸ may be identical or different and independently of one another hydrogen,
C₁-C₆-alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy,
C₁-C₄alkoxy, C₁-C₄alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
C₂-C₆ alkenyl optionally substituted with fluoro, chloro, cyano, amino, mercapto, hydroxy, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₃-C₆-alkynyl, optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₃-C₆-cycloalkyl, optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₅-C₆cycloalkenyl, optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
(C₃-C₆cycloalkyl) - (C₁-C₂-alkyl), optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄alkoxy, C₁ C₄-alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
(C₅-C₆cycloalkenyl) - (C₁-C₂-alkyl), optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄alkoxy, C₁ C₄-alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₁-C₆-alkylcarbonyl, optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄ -alkyl) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
C₂-C₆ alkenylcarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄ alkoxy, oxo, phenyl;
(C₃-C₆-cycloalkyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
(C₅-C₆cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
(C₃-C₆-cycloalkyl) - (C₁-C₂-alkyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
(C₅-C₆cycloalkenyl) - (C₁-C₂-alkyl) carbonyl, optionally substituted by fluorine, chlorine, hydroxy, C₁-C₄-alkoxy, oxo, phenyl;
C₁-C₆-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄-alkylthio;
C₂-C₆ alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, phenyl;
C₂-C₆ alkynyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, phenyl;
C₁-C₆-alkylthiocarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄-alkoxy, phenyl;
C₂-C₆ alkenylthiocarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄ alkoxy, phenyl;
C₁-C₆-alkylamino and di (C₁-C₆-alkyl) aminocarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄-alkoxy, phenyl;
C₂-C₆ alkenylamino and di (C₁-C₆ alkenyl) aminocarbonyl optionally substituted by fluoro, chloro, C₁-C₄ alkoxy, phenyl;
C₁-C₆-alkylsulfonyl, optionally substituted by fluorine, chlorine, C₁-C₄-alkoxy, phenyl;
C₂-C₆ alkenylsulfonyl;
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to three independent radicals R⁵, wherein the alkyl radical may each contain 1 to 4 carbon atoms and R⁵ is as defined above
or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R⁵, where the alkyl radical can contain in each case 1 to 3 C atoms, and
R³ and R⁴ are the same or different, independently of one another
C₁-C₆-alkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy,
C₁-C₄alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfinyl, carboxy, carbamoyl;
C₂-C₆ alkenyl optionally substituted with fluorine or chlorine, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfonyl, C₁-C₄ alkylsulfinyl;
C₃-C₆cycloalkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio, C₁-C₄-alkylsulfonyl, C₁-C₄-alkylsulfinyl;
C₃-C₆cycloalkenyl, optionally substituted by fluorine or chlorine, phenoxy, C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfinyl; or
with up to three mutually independent radicals R 5 substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, where the alkyl radical can contain in each case 1 to 3 C atoms and R⁵ is as defined above,
one of R³ or R⁴ may be hydrogen.
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring having 3 to 6 carbon atoms, which is optionally substituted by fluorine, chlorine, hydroxyl, amino, C₁-C₄-alkyl, C₂-C₄- Alkenyl, C₂-C₄-alkynyl, C₁-C₄-acyloxy, benzoyloxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted. 4. Compounds of the formula I, Ia, Ib or Ic according to one or more of claims 1-3, wherein
4) n zero, or one,
the individual substituents R¹ independently of one another fluorine, chlorine, trifluoromethyl, hydroxy, mercapto, C₁-C₃-alkyl, C₁-C₃-alkoxy, C₁-C₃-alkylthio, amino, C₁-C₃-alkylamino, di (C₁-C₃-alkyl) amino, (C₁-C₂-alkyl) oxycarbonyl (C₁-C₄-alkyl) amino, C₁-C₃-acylamino,
T, U, V and W are CH, CR¹ or N, with at least one and at most two nitrogen atoms in the ring,
X represents oxygen, sulfur or substituted nitrogen N-R 2, where R 2 may have the meanings given below,
Y is O-R⁶, S-R⁶, N-R⁶R⁷ or N = CR⁶R⁷, where R⁶, R⁷ and R⁸ can have the meanings given below,
R₂, R₆, R₇ and R₈ are identical or different and independently of one another hydrogen,
C₁-C₆-alkyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₂-C₆ alkenyl optionally substituted with fluoro, chloro, amino, mercapto, hydroxy, C₁-C₄ acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄ alkoxy, C₁-C₄ alkylamino, di (C₁-C₄ alkyl ) amino, C₁-C₄-alkylthio;
C₃-C₈-alkynyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₃-C₆cycloalkyl, optionally substituted with fluorine, chlorine, C₁-C₄-acyloxy, benzoyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄-alkylthio ;
C₅-C₆-cycloalkenyl,
(C₃-C₆ cycloalkyl) - (C₁-C₂ alkyl),
(C₅-C₆-cycloalkenyl) - (C₁-C₂ alkyl),
C₁-C₆-alkylcarbonyl, optionally substituted by fluorine, chlorine, amino, mercapto, hydroxy, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl ) amino, C₁-C₄-alkylthio;
C₂-C₄-alkenylcarbonyl,
(C₃-C₆ cycloalkyl) carbonyl,
(C₅-C₆-cycloalkenyl) carbonyl,
(C₃-C₆ cycloalkyl) - (C₁-C₂-alkyl) carbonyl,
(C₅-C₆-cycloalkenyl) - (C₁-C₂-alkyl) carbonyl,
C₁-C₆-alkyloxycarbonyl, optionally substituted by fluorine, chlorine, C₁-C₄-alkoxy, C₁-C₄-alkylamino, di (C₁-C₄-alkyl) amino, C₁-C₄-alkylthio;
C₂-C₆ alkenyloxycarbonyl,
C₂-C₆ Alkynyloxycarbonyl,
C₁-Alkylthiocarbonyl,
C₂-C₆ Alkenylthiocarbonyl,
C₁-C₆-alkylamino and di (C₁-C₆-alkyl) aminocarbonyl,
C₂-C₆ alkenylamino and di (C₁-C₄ alkenyl) aminocarbonyl,
C₁-alkylsulfonyl,
C₂-C₆ Alkenylsulfonyl,
or arylcarbonyl, aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, arylalkoxycarbonyl, substituted with up to two independent radicals R⁵, where the alkyl radical can contain in each case 1 to 3 C atoms and R⁵ is as defined above under 3 or with up to two mutually independent radicals R⁵ substituted heteroaryl, heteroarylalkyl, heteroarylalkenyl, Heteroarylalkylcarbonyl or Heteroarylalkenylcarbonyl, wherein the alkyl radical in each case 1 to 2 C-atoms can contain, and
R₃ and R₄ are the same or different, independently of one another
C₁-C₆-alkyl, optionally substituted by fluorine, chlorine, hydroxy, amino, mercapto, C₁-C₄-acyloxy, benzoyloxy, benzyloxy, phenoxy, C₁-C₄-alkoxy,
C₁-C₄alkylamino, di (C₁-C₄alkyl) amino, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₁-C₄alkylsulfinyl, carboxy,
C₂-C₆ alkenyl, optionally substituted with fluorine or chlorine,
C₃-C₆ cycloalkyl,
C₅-C₆cycloalkenyl optionally substituted with fluoro or chloro; or
with up to three mutually independent radicals R⁵ substituted aryl, arylalkyl, heteroaryl or heteroarylalkyl, where the alkyl radical may contain in each case 1 to 2 C atoms and R⁵ is as defined above,
one of R³ or R⁴ may be hydrogen,
R³ and R⁴ may together also represent a radical = C-Z¹Z² linked via a double bond, where Z¹ and Z² have the meaning given above for R³ and R⁴,
R³ and R⁴ or R³ and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring having 3 to 6 carbon atoms, which is optionally substituted by fluorine, chlorine, hydroxyl, amino, C₁-C₄-alkyl, C₂-C₄- Alkenyl, C₂-C₄-alkynyl, C₁-C₄-acyloxy, benzoyloxy, C₁-C₄-alkoxy, C₁-C₄-alkylthio, oxo, thioxo, carboxy, carbamoyl or phenyl may be substituted. 5. A process for the preparation of compounds of formulas I, Ia, Ib and Ic as in claims 1-4, characterized in that

• A) for the preparation of compounds of the formulas I, Ib with X equal to oxygen and Ia, Ic with X as defined under 1) -5) with the exception of N-R² is NHY equal to R⁶, O-R⁶, S-R⁶, N -R⁶R⁷, N = C-R⁶R⁷ or C-R⁶R⁷R⁸ and the radicals R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ as defined under 1) -5)
  a compound of the formula II, IIa, IIb or IIc wherein for R¹, R², R³, R⁴ and R⁵ are the definitions mentioned under 1) -4), with a compound of formula III, Y-NH₂ (III) wherein Y is R⁶, O-R⁶, S-R⁶, N-R⁶R⁷ , N = C-R⁶R⁷ or C-R⁶R⁷R⁸ can mean and for R⁶, R⁷ and R⁸ the definitions mentioned under 1) -4) apply, is implemented or that
• B) Compounds of formulas I, Ia, Ib and Ic with X, Y and the radicals R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ as defined under 1) -5) can be prepared by reaction of a compound of Formula I, Ia, Ib or Ic, wherein for X and the radicals R¹, R², R³, R⁴, R⁵ and R⁶ are the definitions mentioned under 1) -4) and Y is H, OH, SH, NH₂ or NHR⁶ with a reagent of the formula IV, R⁹-Z (IV) where R⁹ has the meanings mentioned above under 1) -4) for R², R⁶, R⁷ and R⁸ with the exception of hydrogen and Z is a leaving group or
• C) compounds of the formulas I and Ib, where X is sulfur and R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are as defined under 1) -4) are prepared by reaction of a compound of formula I or Ib, wherein X is oxygen and for R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ the definitions mentioned under 1) -4) apply, with a sulfurizing reagent or
• D) for the preparation of compounds of formulas I, Ia, Ib and Ic, with X and R¹, R², R³, R⁴ and R⁵ as defined under 1) -4) and Y is O-R⁶, S-R⁶ or N-R⁶R⁷
  Compounds of the formulas I, Ia, Ib or Ic with X and R¹, R², R³, R⁴ and R⁵ as defined under 1) -5) and Y is OH, SH, NH₂ or NHR⁶ with a compound of the formula V, R⁹- OH (V) where R⁹
  Alkyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Alkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Alkynyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Cycloalkyl optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Cycloalkenyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  (Cycloalkyl) - (alkyl), optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl,
  (Cycloalkenyl) - (alkyl), optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo , Carboxy, carbamoyl,
  Alkylcarbonyl, optionally substituted by fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl,
  Alkenylcarbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkenyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkyl) - (alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl,
  (Cycloalkenyl) - (alkyl) carbonyl, optionally substituted by fluorine, chlorine or hydroxyl, alkoxy, oxo, phenyl,
  or with up to five mutually independent radicals R⁵ substituted aryl, arylcarbonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, arylalkenylcarbonyl, wherein R⁵ is as defined above
  or with up to three independent radicals R⁵ substituted heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl, be reacted in the presence of a dehydrating agent or
• E) compounds of the formulas I and Ib where X is oxygen and Y, R¹, R², R³, R⁴ and R⁵ are as defined under 1) -4), by cyclization of a compound of the formula VI, with Y, R¹, R², R³, R⁴ and R⁵ as defined under 1) -4) and Z is a leaving group are prepared.

6. Compounds according to one or more of claims 1-4 for use as a medicine. 7. A pharmaceutical composition containing an effective amount of at least one compound according to one or more of claims 1-4. 8. A process for the preparation of a medicament according to claim 7, characterized characterized in that the effective amount of a compound according to one or several of claims 1-4 with conventional pharmaceutical excipients in one appropriate dosage form is brought. 9. Use of compounds according to one or more of claims 1-4 for the manufacture of medicaments for the treatment of viral diseases.