Sulfonic amide and sulfoximine-substituted diaryl-dihydropyrimidinones and usage thereof

1. A compound of the formula (I)

in which

Z represents a sulfonamide grouping of the formula

or represents a sulfoximine grouping of the formula

in which

* denotes the point of attachment to the phenyl ring,

R Z1 represents hydrogen, or represents (C 1 -C 6 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino and up to three times by fluorine,

R Z2 represents hydrogen, (C 3 -C 6 )-cycloalkyl, 4- to 6-membered heterocyclyl or 5- or 6-membered heteroaryl

or

represents (C 1 -C 6 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino, (C 1 -C 4 )-alkylcarbonylamino, (C 1 -C 4 )-alkoxycarbonylamino, (C 1 -C 4 )-alkylsulfinyl, (C 1 -C 4 )-alkylsulfonyl, (C 3 -C 6 )-cycloalkyl, phenyl, 4- to 6-membered heterocyclyl, 5- or 6-membered heteroaryl or a group of the formula —C(═O)—NR Z5 R Z6 and up to three times by fluorine,

where the alkoxy substituent mentioned for its part may be substituted up to three times by fluorine,

and where

the heterocyclyl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of fluorine, (C 1 -C 4 )-alkyl, oxo, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono- and di-(C 1 -C 4 )-alkylamino

and

the phenyl group mentioned and the heteroaryl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, difluoromethyl, trifluoromethyl and (C 1 -C 4 )-alkoxy,

and where

R Z5 and R Z6 are identical or different and independently of one another represent hydrogen or (C 1 -C 4 )-alkyl

or

R Z5 and R Z6 together with the nitrogen atom to which they are attached form a 4- to 6-membered aza heterocycle which may contain a further ring heteroatom from the group consisting of N, O and S and may be substituted by (C 1 -C 4 )-alkyl, oxo, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino,

or

R Z1 and R Z2 together with the nitrogen atom to which they are attached form a 4- to 10-membered aza heterocycle which may contain a further ring heteroatom from the group consisting of N, O and S and may be substituted up to two times by identical or different substituents from the group consisting of fluorine, (C 1 -C 4 )-alkyl, oxo, hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono- and di-(C 1 -C 4 )-alkylamino,

R Z3 represents (C 1 -C 6 )-alkyl which may be substituted by (C 3 -C 6 )-cycloalkyl or up to three times by fluorine, or represents phenyl which may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, difluoromethyl and trifluoromethyl, or represents (C 3 -C 6 )-cycloalkyl,

and

R Z4 represents hydrogen, (C 1 -C 4 )-alkyl or (C 3 -C 6 )-cycloalkyl,

R 1 represents cyano or acetyl,

R 2 represents hydrogen, represents (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkylsulfonyl which may be substituted up to three times by fluorine, or represents a group of the formula —CH 2 —C(═O)—NH—R 4 in which

R 4 represents hydrogen, represents (C 1 -C 4 )-alkyl which may be substituted by (C 3 -C 6 )-cycloalkyl or up to three times by fluorine, or represents (C 3 -C 6 )-cycloalkyl,

and

R 3 represents hydrogen, fluorine or chlorine,

or a salt, a solvate or a solvate of a salt thereof.

2. The compound of claim 1 in which

Z represents a sulfonamide grouping of the formula

or represents a sulfoximine grouping of the formula

in which

* denotes the point of attachment to the phenyl ring,

R Z1 represents hydrogen or represents (C 1 -C 4 )-alkyl which may be substituted by hydroxyl, methoxy or ethoxy,

R Z2 represents hydrogen, (C 3 -C 6 )-cycloalkyl, 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl

or

represents (C 1 -C 4 )-alkyl which may be substituted by hydroxyl, (C 1 -C 4 )-alkoxy, amino, mono- or di-(C 1 -C 4 )-alkylamino, (C 1 -C 4 )-alkylcarbonylamino, (C 1 -C 4 )-alkoxycarbonylamino, (C 1 -C 4 )-alkylsulfinyl, (C 1 -C 4 )-alkylsulfonyl, (C 3 -C 6 )-cycloalkyl, phenyl, 5- or 6-membered heterocyclyl, 5- or 6-membered heteroaryl or a group of the formula —C(═O)—NR Z5 R Z6 and up to three times by fluorine,

where the alkoxy substituent mentioned for its part may be substituted up to three times by fluorine,

and where

the heterocyclyl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of (C 1 -C 4 )-alkyl, oxo, hydroxyl and (C 1 -C 4 )-alkoxy

and

the phenyl group mentioned and the heteroaryl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl and (C 1 -C 4 )-alkoxy,

and where

R Z5 and R Z6 are identical or different and independently of one another represent hydrogen or (C 1 -C 4 )-alkyl

or

R Z5 and R Z6 together with the nitrogen atom to which they are attached form a 5- or 6-membered aza heterocycle which may contain a further ring heteroatom from the group consisting of N and O and may be substituted by (C 1 -C 4 )-alkyl, oxo, hydroxyl or (C 1 -C 4 )-alkoxy,

or

R Z1 and R Z2 together with the nitrogen atom to which they are attached form a 5- to 10-membered aza heterocycle which may contain a further ring heteroatom from the group consisting of N and O and may be substituted up to two times by identical or different substituents from the group consisting of (C 1 -C 4 )-alkyl, oxo, hydroxyl and (C 1 -C 4 )-alkoxy,

R Z3 represents (C 1 -C 4 )-alkyl which may be substituted by (C 3 -C 6 )-cycloalkyl or up to three times by fluorine, or represents phenyl which may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, methyl and trifluoromethyl, or represents (C 3 -C 6 )-cycloalkyl,

and

R Z4 represents hydrogen, methyl or cyclopropyl,

R 1 represents cyano,

R 2 represents hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkylsulfonyl, each of which may be substituted up to three times by fluorine, or represents a group of the formula —CH 2 —C(═O)—NH—R 4 in which

R 4 represents hydrogen, methyl, cyclopropyl or cyclopropylmethyl,

and

R 3 represents hydrogen or fluorine,

or a salt, a solvate or a solvate of a salt thereof.

3. The compound of claim 1 in which

Z represents a sulfonamide grouping of the formula

in which

* denotes the point of attachment to the phenyl ring,

R Z1 represents hydrogen, methyl or 2-hydroxyethyl,

R Z2 represents hydrogen, cyclopropyl, 5- or 6-membered heterocyclyl or 5- or 6-membered heteroaryl

or

represents (C 1 -C 4 )-alkyl which may be substituted by hydroxyl, methoxy, ethoxy, amino, methylamino, ethylamino, dimethylamino, diethylamino, acetylamino, cyclopropyl, 5- or 6-membered heterocyclyl or a group of the formula —C(═O)—NR Z5 R Z6 ,

where methoxy and ethoxy substituents mentioned for their part may be substituted up to three times by fluorine,

and where

the heterocyclyl groups mentioned may be substituted up to two times by identical or different substituents from the group consisting of methyl, ethyl, oxo, hydroxyl, methoxy and ethoxy

and

the heteroaryl group mentioned may be substituted up to two times by identical or different substituents from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy and ethoxy,

and where

R Z5 and R Z6 independently of one another represent hydrogen or methyl or together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or morpholine ring,

or

R Z1 and R Z2 together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or morpholine ring,

R 1 represents cyano,

R 2 represents hydrogen, methyl, methylsulfonyl or the group of the formula —CH 2 —C(═O)—NH 2 ,

and

R 3 represents hydrogen,

or a salt, a solvate or a solvate of a salt thereof.

4. The compound of claim 1 in which

Z represents a sulfoximine grouping of the formula

in which

* denotes the point of attachment to the phenyl ring

and

R Z3 represents (C 1 -C 4 )-alkyl which may be substituted by cyclopropyl or up to three times by fluorine, or represents cyclopropyl,

R 1 represents cyano,

R 2 represents hydrogen, methyl, methylsulfonyl or the group of the formula —CH 2 —C(═O)—NH 2 ,

and

R 3 represents hydrogen,

or a salt, a solvate or a solvate of a salt thereof.

5. The compound of claim 1 in which

Z represents a sulfonamide grouping of the formula

in which

* denotes the point of attachment to the phenyl ring

and

R Z2 represents hydrogen, methyl or the group of the formula —CH 2 —C(═O)—NH 2 ,

R 1 represents cyano,

R 2 represents hydrogen, methyl or methylsulfonyl,

and

R 3 represents hydrogen,

or a salt, a solvate or a solvate of a salt thereof.

6. The compound of claim 1 in which

Z represents a sulfoximine grouping of the formula

in which

* denotes the point of attachment to the phenyl ring,

R 1 represents cyano,

R 2 represents hydrogen, methyl or methylsulfonyl,

and

R 3 represents hydrogen,

or a salt, a solvate or a solvate of a salt thereof.

7. A process for preparing a compound of the formula (I) of claim 1 , in which

Z represents a sulfonamide grouping of the formula

in which

* denotes the point of attachment to the phenyl ring

and

R Z1 and R Z2 have the meanings given in claim 1 ,

comprising:

converting an aniline derivative of the formula (II)

in which R 1 , R 2 and R 3 have the meanings given in claim 1 ,

with sodium nitrite and hydrochloric acid into the corresponding diazonium salt and reacting the diazonium salt in a one-pot reaction with sulfur dioxide in the presence of copper(I) chloride to give a sulfonyl chloride of the formula (III)

in which R 1 , R 2 and R 3 have the meanings given above,

reacting the sulfonyl chloride of the formula (III) with an amine of the formula (IV)

in which R Z1 and R Z2 have the meanings given in any of claims 1 , 2 , 3 and 5 ,

if appropriate in the presence of an auxiliary base, to give the sulfonamide of the formula (I-A)

in which R 1 , R 2 , R 3 , R Z1 and R Z2 have the meanings given above,

and optionally, separating compounds of the formula (I-A) obtained in this manner by methods known to the person skilled in the art into their enantiomers and/or diastereomers and/or converted with the appropriate (i) solvents and/or (ii) bases or acids into their solvates, salts and/or solvates of the salts.

8. A process for preparing a compound of the formula (I) of claim 1 , in which

Z represents a sulfoximine grouping of the formula

in which

* denotes the point of attachment to the phenyl ring

and

R Z3 has the meaning given in any of claims 1 , 2 , 4 and 6 ,

comprising,

oxidizing a phenyl thioether derivative of the formula (V)

in which R 1 , R 2 , R 3 and R Z3 have the meanings given in any of claims 1 , 2 , 4 and 6 ,

with hydrogen peroxide, a peracid or a periodate to give the sulfoxide of the formula (VI)

in which R 1 , R 2 , R 3 and R Z3 have the meanings given above,

converting the sulfoxide of formula (VI) with 2,2,2-trifluoroacetamide and (diacetoxyiodo)benzene in the presence of dimeric rhodium(II) acetate as catalyst and magnesium oxide as base into an N-acylsulfoximine of the formula (VII)

in which R 1 , R 2 , R 3 and R Z3 have the meanings given above,

and removing the trifluoroacetyl group in the N-acylsulfoximine of the formula (VII) under basic conditions to give the sulfoximine of the formula (I-B)

in which R 1 , R 2 , R 3 and R Z3 have the meanings given above,

and optionally separating the compounds of the formula (I-B) obtained in this manner by methods known to the person skilled in the art into their enantiomers and/or diastereomers and/or converted with the appropriate (i) solvents and/or (ii) bases or acids into their solvates, salts and/or solvates of the salts.

9. A pharmaceutical composition comprising a compound of claim 1 in combination with one or more inert non-toxic pharmaceutically acceptable auxiliaries.