Phenylsulfonylamide pyrimidine

A compound of the formula ##STR14## wherein R.sup.1 is hydrogen, lower-alkyl, lower-alkoxy, lower-alkylthio, halogen or trifluoromethyl;

• R.sup.2 is hydrogen, lower-alkyl, halogen, lower-alkoxy, trifluoromethyl or --OCH.sub.2 COOR.sup.9 ;
• R.sup.3 is hydrogen, lower-alkyl, halogen, lower-alkylthio, trifluoromethyl, lower-alkoxy or trifluoromethoxy;
• R.sup.2 and R.sup.3 together are butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• R.sup.4 is hydrogen, lower-alkyl, trifluoromethyl, lower-alkoxy, lower-alkylthio, hydroxy-lower-alkyl, hydroxy-lower-alkoxy, hydroxy-lower-alkoxy-lower-alkyl, hydroxy-lower-alkoxy-lower-alkoxy, alkoxy-lower-alkyl, alkoxy-lower-alkyloxy, lower-alkylsulfinyl, lower-alkylsulfonyl, 2-methoxy-3-hydroxypropoxy, 2-hydroxy-3-phenylpropyl, amino-lower-alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, amino, lower-alkyl-amino, di-lower-alkylamino, arylamino, aryl, arylthio, aryloxy, aryl-lower-alkyl, heterocyclyl, heterocyclyl-lower-alkyl, heterocyclyl-amino, heterocyclylthio, heterocyclyloxy, --CHO, --CH.sub.2 OH or --CH.sub.2 Cl;
• R.sup.5 to R.sup.8 are independently hydrogen, halogen, trifluoromethyl, lower-alkoxy, lower-alkylthio or cyano;
• R.sup.6 and R.sup.5 or R.sup.7 together are butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• X is --O--or --S--;
• Y is --CHO, C.sub.1-4 -alkyl, --(CH.sub.2).sub.1-4 --, Z--R.sup.9, --(CH.sub.2).sub.1-4 --OC(O) (CH.sub.2).sub.1-4 CH.sub.3, --(CH.sub.2).sub.1-4 OC(O)Het, --(CH.sub.2).sub.1-4 NHC(O) R.sup.10, --(CH.sub.2).sub.1-4 OCH.sub.2 CH(OH)CH.sub.2 OH and cyclic ketals thereof, --(CH.sub.2).sub.1-4 NR.sup.9 CH.sub.2 CH(OH)CH.sub.2 OH, --(CH.sub.2 ).sub.1-4 OCH.sub.2 CH.sub.2 SCH.sub.3, --(CH.sub.2).sub.1-4 OCH.sub.2 CH.sub.2 S (O)CH.sub.3, CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 -ZH, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 OC(O)R.sup.10, --(CH.sub.2).sub.1-4 NR.sup.9 (CH.sub.2).sub.1-4 -ZH, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 OC(O)Het, --(CH.sub.2).sub.0-3 CH(OH)R.sup.10, --(CH.sub.2).sub.0-3 CH(OH)(CH.sub.2).sub.1-4 ZH, --(CH.sub.2).sub.0-3)CH(OH)CH.sub.2 SCH.sub.3, --(CH.sub.2).sub.0-3 CH(OH)CH.sub.2 S(O)CH.sub.3, --(CH.sub.2).sub.0-3 CH(OH)OCH.sub.2 CH.sub.2 OH, --(CH.sub.2).sub.0-3 C(O) (CH.sub.2).sub.1-4 CH.sub.3, --(CH.sub.2).sub.0-3 C(O) (CH.sub.2).sub.1-4 Z R.sup.11, --(CH.sub.2).sub.0-3 C(O)CH.sub.2 Hal, --(CH.sub.2).sub.1-4 Hal, --(CH.sub.2).sub.1-4 CN, --(CH.sub.2).sub.0-3 C(O)OR.sup.9, --OR.sup.12 or --SR.sup.12 ;
• R.sup.9 is hydrogen or C.sub.1-4 -alkyl;
• R.sup.10 is C.sub.1-4 -alkyl;
• R.sup.11 is hydrogen, C.sub.1-4 -alkanoyl or heterocyclylcarbonyl;
• R.sup.12 is C.sub.1-4 -alkyl or --(CH.sub.2).sub.0-4 -aryl;
• Z is --O--, --S-- or --NR.sup.9 --;
• Het is a heterocyclic residue;
• Hal is halogen;
• and
• n is 0 or 1;
• wherein aryl is phenyl and phenyl substituted with halogen, lower-alkyl, lower-alkoxy, carboxyl, or trifluoromethyl and heterocycle is mono- or bicyclic 5- and 6- membered heterocyclic residues which are unsubstituted or which are mono- or disubstituted by lower-alkyl, lower-alkoxy, halogen, aryl or aryl-lower-alkyl and which have oxygen, nitrogen or sulphur as the hetero atom or a salt thereof.

A pharmaceutical composition comprising an effective amount of a compound of the formula ##STR15## wherein R.sup.1 is hydrogen, lower-alkyl, lower-alkoxy, lower-alkylthio, halogen or trifluoromethyl;

• R.sup.2 is hydrogen, lower-alkyl, halogen, lower-alkoxy, trifluoromethyl or --OCH.sub.2 COOR.sup.9 ;
• R.sup.3 is hydrogen, lower-alkyl, halogen, lower-alkylthio, trifluoromethyl, lower-alkoxy or trifluoromethoxy;
• R.sup.2 and R.sup.3 together are butadienyl, methylenedioxy, ethylene-dioxy or isopropylidenedioxy;
• R.sup.4 is hydrogen, lower-alkyl, trifluoromethyl, lower-alkoxy, lower-alkylthio, hydroxy-lower-alkyl, hydroxy-lower-alkoxy, hydroxy-lower-alkoxy-lower-alkyl, hydroxy-lower-alkoxy-lower alkoxy, alkoxy-lower-alkyl, alkoxy-lower-alkyloxy, lower-alkylsulfinyl, lower-alkylsulfonyl, 2-methoxy-3-hydroxypropoxy, 2-hydroxy-3-phenylpropyl, amino-lower-alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, amino, lower-alkyl-amino, di-lower-alkylamino, arylamino, aryl, arylthio, aryloxy, aryl-lower-alkyl, heterocyclyl, heterocyclyl-lower-alkyl, heterocyclyl-amino, heterocyclylthio, heterocyclyloxy, --CHO, --CH.sub.2 OH or --CH.sub.2 Cl;
• R.sup.5 to R.sup.8 are independently hydrogen, halogen, trifluoromethyl, lower-alkoxy, lower-alkylthio or cyano;
• R.sup.6 and R.sup.5 or R.sup.7 together are butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• X is --O--or --S--;
• Y is --CHO, C.sub.1-4 -alkyl, --(CH.sub.2).sub.1-4 -Z--R.sup.9, --(CH.sub.2).sub.1-4 --OC(O)(CH.sub.2).sub.1-4 CH.sub.3, --(CH.sub.2).sub.1-4 OC(O)Het, --(CH.sub.2).sub.1-4 NHC(O)R.sup.10, --(CH.sub.2).sub.1-4 OCH.sub.2 CH (OH) CH.sub.2 OH and cyclic ketals thereof, --(CH.sub.2).sub.1-4 NR.sup.9 CH.sub.2 CH(OH)CH.sub.2 OH, --(CH.sub.2).sub.1-4 OCH.sub.2 CH.sub.2 SCH.sub.3, --(CH.sub.2).sub.1-4 OCH.sub.2 CH.sub.2 S(O)CH.sub.3, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 -ZH, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 OC(O)R.sup.10, --(CH.sub.2).sub.1-4 NR.sup.9 (CH.sub.2).sub.1-4 -ZH --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 OC(O)Het, --(CH.sub.2).sub.0-3 CH(OH)R.sup.10, --(CH.sub.2) --(CH.sub.2).sub.0-3 CH(OH)(CH.sub.2).sub.1-4 ZH, --(CH.sub.2).sub.0-3 CH(OH)CH.sub.2 SCH.sub.3, --(CH.sub.2).sub.0-3 CH(OH)CH.sub.2 S(O)CH.sub.3, --(CH.sub.2).sub.0-3 CH(OH)OCH.sub.2 CH.sub.2 OH, --(CH.sub.2).sub.0-3 C(O)(CH.sub.2).sub.1-4 CH.sub.3, --(CH.sub.2).sub.0-3 C(O)(CH.sub.2).sub.1-4 Z R.sup.11, --(CH.sub.2).sub.0-3 C(O)CH.sub.2 Hal, --(CH.sub.2).sub.1-4 Hal, --(CH.sub.2).sub.1-4 CN, --(CH.sub.2).sub.0-3 C(O)OR.sup.9, --OR.sup.12 or --SR.sup.12 ;
• R.sup.9 is hydrogen or C.sub.1-4 -alkyl;
• R.sup.10 is C.sub.1-4 -alkyl;
• R.sup.11 is hydrogen, C.sub.1-4 -alkanoyl or heterocyclylcarbonyl;
• R.sup.12 is C.sub.1-4 -alkyl or --(CH.sub.2).sub.0-4 -aryl;
• Z is --O--, --S-- or --NR.sup.9 --;
• Het is a heterocyclic residue;
• Hal is halogen;
• and
• n is 0 or 1;
• wherein aryl is phenyl and phenyl substituted with halogen, lower-alkyl, lower-alkoxy, carboxyl or trifluoromethyl and heterocycle is mono- or bicyclic 5- and 6- membered heterocyclic residues which are unsubstituted or which are mono- or di-substituted by lower-alkyl, lower-alkoxy, halogen, aryl or aryl-lower-alkyl and which have oxygen, nitrogen or sulphur as the hetero atom
• or a salt thereof and a pharmaceutical carrier material.

A process for the manufacture of a compound of the formula ##STR16## wherein R.sup.1 is hydrogen, lower-alkyl, lower-alkoxy, lower-alkylthio, halogen or trifluoromethyl;

• R.sup.2 is hydrogen, lower-alkyl, halogen, lower-alkoxy, trifluoromethyl or --OCH.sub.2 COOR.sup.9 ;
• R.sup.3 is hydrogen, lower-alkyl, halogen, lower-alkylthio, trifluoromethyl, lower-alkoxy or trifluoromethoxy;
• R.sup.2 and R.sup.3 together are butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• R.sup.4 is hydrogen, lower-alkyl, trifluoromethyl, lower-alkoxy, lower-alkylthio, hydroxy-lower-alkyl, hydroxy-lower-alkoxy, hydroxy-lower-alkoxy-lower-alkyl, hydroxy-lower-alkoxy-lower-alkoxy, alkoxy-lower-alkyl, alkoxy-lower-alkyloxy, lower-alkylsulfinyl, lower-alkylsulfonyl, 2-methoxy-3-hydroxypropoxy, 2-hydroxy-3-phenylpropyl, amino-lower-alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, amino, lower-alkyl-amino, di-lower-alkylamino, arylamino, aryl, arylthio, aryloxy, aryl-lower-alkyl, heterocyclyl, heterocyclyl-lower-alkyl, heterocyclyl-amino, heterocyclylthio, heterocyclyloxy, --CHO, --CH.sub.2 OH or --CH.sub.2 Cl;
• R.sup.5 to R.sup.8 are independently hydrogen, halogen, trifluoro-methyl, lower-alkoxy, lower-alkylthio or cyano;
• R.sup.6 and R.sup.5 or R.sup.7 together are butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• X is --O--or --S--;
• Y is --CHO, C.sub.1-4 -alkyl, --(CH.sub.2).sub.1-4 -Z--R.sup.9, --(CH.sub.2).sub.1-4 --OC(O)(CH.sub.2).sub.1-4 CH.sub.3, --(CH.sub.2).sub.1-4 OC(O)Het, --(CH.sub.2).sub.1-4 NHC(O) R.sup.10, --(CH.sub.2).sub.1-4 OCH.sub.2 CH(OH)CH.sub.2 OH and cyclic ketals thereof, --(CH.sub.2).sub.1-4 NR.sup.9 CH.sub.2 CH(OH)CH.sub.2 OH, --(CH.sub.2).sub.1-4 OCH.sub.2 CH.sub.2 SCH.sub.3, --(CH.sub.2).sub.1-4 OCH.sub.2 CH.sub.2 S(O)CH.sub.3, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 -ZH, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 OC(O)R.sup.10, --(CH.sub.2).sub.1-4 NR.sup.9 (CH.sub.2).sub.1-4 -ZH, --(CH.sub.2).sub.1-4 O(CH.sub.2).sub.1-4 OC(O)Het, --(CH.sub.2).sub.0-3 CH(OH)R.sup.10, --(CH.sub.2).sub.0-3 CH(OH) (CH.sub.2).sub.1-4 ZH, --(CH.sub.2).sub.0-3 CH(OH)CH.sub.2 SCH.sub.3, --(CH.sub.2).sub.0-3 CH(OH)CH.sub.2 S(O)CH.sub.3 , --(CH.sub.2).sub.0-3 CH(OH)OCH.sub.2 CH.sub.2 OH, --(CH.sub.2).sub.0-3 C(O)(CH.sub.2).sub.1-4 CH.sub.3, --(CH.sub.2).sub.0-3 C(O)(CH.sub.2).sub.1-4 Z R.sup.11, --(CH.sub.2).sub.0-3 C(O)CH.sub.2 Hal, --(CH.sub.2).sub.1-4 Hal, --(CH.sub.2).sub.1-4 CN, --(CH.sub.2).sub.0-3 C(O)OR.sup.9, --OR.sup.12 or --SR.sup.12 ;
• R.sup.9 is hydrogen or C.sub.1-4 -alkyl;
• R.sup.10 is C.sub.1-4 -alkyl;
• R.sup.11 is hydrogen, C.sub.1-4 -alkanoyl or heterocyclylcarbonyl;
• R.sup.12 is C.sub.1-4 -alkyl or --(CH.sub.2).sub.0-4 -aryl;
• Z is --O--, --S-- or --NR.sup.9 --;
• Het is a heterocyclic residue;
• Hal is halogen;
• and
• n is 0 or 1;
• wherein aryl is phenyl and phenyl substituted with halogen, lower-alkyl, lower-alkoxy, carboxyl or trifluoromethyl and heterocycle is mono- or bicyclic 5- and 6- membered heterocyclic residues which are unsubstituted or which are mono- or di-substituted by lower-alkyl, lower-alkoxy, halogen, aryl or aryl-lower-alkyl and which have oxygen, nitrogen or sulphur as the hetero atom or a salt thereof which process comprises
• a) reacting a compound of the formula ##STR17## wherein R.sup.1 -R.sup.8, X and n have the significance given earlier in this claim and Hal is halogen, with a compound of the formula
• R.sup.12 AM III
• wherein A is oxygen or sulphur and M is an alkali metal, to give a compound of formula I in which Y is the residue --OR.sup.12 or --SR.sup.12 ;
• or
• b) reacting a compound of the formula ##STR18## wherein R.sup.4 -R.sup.8, R.sup.10, X and n have the significance given earlier in this claim, with a compound of the formula ##STR19## wherein R.sup.1, R.sup.2, R.sup.3 and M have the significance given earlier
• in this claim, to give a compound of formula I in which Y is a residue R.sup.10 and R.sup.1 -R.sup.8, X and n have the significance given above, if desired, oxidizing a compound of formula I obtained in which Y and/or R.sup.4 is a residue CH.sub.3 to give a compound of formula I in which Y and/or R.sup.4 is a residue CHO and, if desired, converting the residue CHO into a different residue Y and/or R.sup.4 ;
• or
• c) reacting a compound of the formula ##STR20## wherein R.sup.1, R.sup.2, R.sup.3 and Hal has the significance given earlier in this claim, with a compound of the formula ##STR21## wherein R.sup.4 -R.sup.8, R.sup.12, n, A and X have the significance given earlier in this claim, and, if desired, converting the compound of formula I obtained into a salt.