Sulphoximine-substituted quinazoline derivatives as immuno-modulators, their preparation and use as medicaments
View Patent ↗The present invention relates to sulphoximine-substituted quinazoline derivatives of the formula (I), processes for their preparation and their use as a medicament for the treatment of various diseases.
1. A compound of formula (I):
in which
R 1 represents
(i) an aryl or heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , —NR 6 —C(O)—R 11 , —NR 6 —C(O)—OR 11 , —NR 6 —C(O)—NR 7 R 8 , —NR 7 —SO 2 —R 11 , cyano, halogen, C 1 C 6 -alkoxy, —OCF 3 , —CF 3 , C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, and/or heterocyclyl having 3 to 8 ring atoms,
(ii) a C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, or C 2 -C 6 -alkynyl, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , —NR 6 —C(O)R 11 , —NR 6 —C(O)—OR 11 , —NR 6 —C(O)—NR 7 R 8 , —NR 6 —SO 2 —R 11 , cyano, halogen, C 1 -C 6 -alkoxy, —OCF 3 , —CF 3 , C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, and/or heterocyclyl, or
(iii) a C 3 -C 8 cycloalkyl or heterocyclyl ring having 3 to 8 ring atoms, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , —NR 6 —C(O)—R 11 , —NR 6 —C(O)—OR 11 , —NR—C(O)—NR 7 R 8 , —NR 6 —SO 2 —R 11 , cyano, halogen, C 1 -C 6 -alkoxy, —OCF 3 , —CF 3 , C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, and/or heterocyclyl having 3 to 8 ring atoms;
R 2 represents
(i) hydrogen,
(ii) hydroxyl, halogen, cyano, nitro, —CF 3 , —OCF 3 , —C(O)OR 11 , —C(O)OH, —C(O)NR 7 R 8 , —C(S)NR 7 R 8 , —NR 7 R 8 , —NR 6 —C(O)—OR 11 , —NR 6 —C(O)—OR 11 , —NR 6 —C(O)—NR 7 R 8 , —NR 6 —SO 2 —R 11 ,
(iii) C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy, which in each case is optionally, identically or differently, mono- or polysubstituted by halogen, hydroxyl, C 1 -C 6 -alkoxy, —CF 3 , —OCF 3 , or —NR 7 R 8 , or
(iv) a C 3 -C 8 -cycloalkyl ring which is optionally, identically or differently, mono- or polysubstituted by halogen, hydroxyl, C 1 -C 6 -alkoxy, —CF 3 , —OCF 3 , —NR 7 R 8 , and/or C 1 -C 6 -alkyl;
R 3 represents a C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, a C 3 —C 7 -cycloalkyl, aryl ring, a heterocyclyl ring having 3 to 8 ring atoms, or a monocyclic heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —C(O)OR 11 , —C(O)NR 7 R 8 , —NR 7 R 8 , cyano, halogen, —CF 3 , C 1 -C 6 -alkoxy, —OCF 3 , and/or C 1 -C 6 -alkyl;
R 4 represents hydrogen, —SO 2 R 11 , —C(O)R 11 , C(O)OR 11 , —C(O)NR 7 R 8 , —C(S)OR 11 , —C(S)NR 7 R 8 or —R 11 ;
X, Y independently of one another represent —O— or —NR 5 —;
A represents
(i) a bond, or
(ii) an aryl or heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , —NR 6 —C(O)—R 11, —C(O)NR 7 R 8 , —NR 6 —C(O)—OR 11 , —NR 6 —C(O)—NR 7 R 8 , —NR 6 —SO 2 —R 11 , cyano, halogen, C 1 -C 6 -alkoxy, —OCF 3 , —CF 3 , C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, and/or heterocyclyl having 3 to 8 ring atoms;
n represents 1-6;
R 5 represents hydrogen;
R 6 represents hydrogen or a C 1 -C 6 -alkyl radical;
R 7 and R 8 independently of one another represent
(i) hydrogen, and/or
(ii) C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 3 -C 8 -cycloalkyl, aryl ring, a heterocyclyl ring having 3 to 8 ring atoms, and/or a heteroaryl ring, and in each case are optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 9 R 10 , cyano, halogen, —CF 3 , C 1 -C 6 -alkoxy, and/or —OCF 3 , or
R 7 and R 8 together with the nitrogen atom form a 5- to 7-membered ring, which optionally in addition to the nitrogen atom contains 1 or 2 further heteroatoms, and which is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 9 R 10 , cyano, halogen, —CF 3 , C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, and/or —OCF 3 ;
R 9 and R 10 independently of one another each represent hydrogen or C 1 -C 6 -alkyl, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl; and
R 11 represents a C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, aryl ring, a heterocyclyl ring having 3 to 8 ring atom, or a heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, halogen, cyano, nitro, —NR 7 R 8 , C 1 -C 6 -alkyl , —CF 3 , C 1 -C 6 -alkoxy, and/or —OCF 3 ;
or a pharmaceutically acceptable salt thereof, or a diastereomer or enantiomer thereof.
2. A compound according to claim 1 , in which
R 1 represents
(i) an aryl or heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , cyano, halogen, C 1 -C 6 -alkoxy, —NR 6 —C(O)R 11 , —OCF 3 , —CF 3 , or C 1 -C 6 -alkyl,
(ii) a C 1 -C 6 -alkyl, which is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , cyano, halogen, C 1 -C 6 -alkoxy, —NR 6 —C(O)R 11 , —OCF 3 , —CF 3 , or C 1 -C 6 -alkyl, or
(iii) a C 3 -C 8 cycloalkyl or heterocyclyl ring having 3 to 8 ring atoms and optionally identically or differently mono- or polysubstituted by hydroxyl, —NR 7 R 8 , cyano, halogen, C 1 -C 6 -alkoxy, —OCF 3 , —CF 3 , C 1 -C 6 -alkyl,
R 2 represents hydrogen, halogen, cyano, —C(O)OR 11 , —C(O)OH, or —C(O)NR 7 R 8 , or C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy which in each case is optionally, identically or differently, mono- or polysubstituted by halogen, hydroxyl, C 1 -C 6 -alkoxy, —CF 3 , —OCF 3 , or —NR 7 R 8 ,
R 3 represents a C 1 -C 6 -alkyl or a C 3 —C 7 -cycloalkyl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —C(O)OR 11 , —C(O)NR 7 R 8 , —NR 7 R 8 , cyano, halogen, —CF 3 , C 1 -C 6 -alkoxy, —OCF 3 and/or C 1 -C 6 -alkyl,
R 4 represents hydrogen, —SO 2 R 11 , —C(O)OR 11 , or —C(O)NR 7 R 8 ,
X represents —NR 5 —,
Y represents —O— or NR 5 ,
A represents
(i) a bond or
(ii) an aryl or heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , —C(O)NR 7 R 8 , cyano, halogen, C 1 -C 6 -alkoxy, —OCF 3 , —CF 3 , C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, and/or heterocyclyl having 3 to 8 ring atoms,
n represents 1-5,
R 7 and R 8 independently of one another represent hydrogen, or and/or a C 1 -C 6 -alkyl radical, C 3 -C 8 -cycloalkyl, aryl ring, a heterocyclyl ring having 3 to 8 ring atoms, and/or a heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 9 R 10 , cyano, halogen, —CF 3 , C 1 -C 6 -alkoxy, and/or OCF 3 , and
R 11 represents a C 1 -C 3 -alkyl, a C 3 -C 8 -cycloalkyl, aryl ring, a heterocyclyl ring having 3 to 8 ring atoms, or a heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, halogen, cyano, nitro, —NR 7 R 8 , C 1 -C 6 -alkyl , —CF 3 , C 1 -C 6 -alkoxy, and/or —OCF 3 .
3. A compound according to claim 1 , in which
R 1 represents
(i) a phenyl or monocyclic heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 6 —C(O)—R 11 , cyano, or C 1 -C 6 -alkyl,
(ii) a C 1 -C 6 -alkyl radical which is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , C 1 -C 6 -alkoxy, and/or C 3 -C 6 -cycloalkyl, or
(iii) a C 3 -C 8 cycloalkyl ring.
4. A compound according to claim 1 , in which R 2 represents hydrogen, halogen, cyano, —C(O)OR 11 , —C(O)OH or a C 1 -C 6 -alkoxy radical.
5. A compound according to claim 1 , in which R 3 represents a C 1 -C 3 -alkyl radical.
6. A compound according to claim 1 , in which R 4 represents hydrogen, —SO 2 R 11 or —C(O)OR 11 .
7. A compound according to claim 1 , in which R 4 represents hydrogen.
8. A compound according to claim 1 , in which A represents a bond or a phenyl or monocyclic heteroaryl ring.
9. A compound according to claim 1 , in which X represents —NH—.
10. A compound according to claim 1 , in which R 7 and R 8 independently of one another represent a C 1 -C 6 -alkyl radical.
11. A compound according to claim 1 , in which n represents 1-4.
12. A compound according to claim 1 in which
R 1 represents
(i) a phenyl or monocyclic heteroaryl ring, which in each case is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 6 —C(O)—R 11 , cyano, or C 1 -C 6 -alkyl, or
(ii) a C 1 -C 6 -alkyl radical which is optionally, identically or differently, mono- or polysubstituted by hydroxyl, —NR 7 R 8 , C 1 -C 6 -alkoxy, and/or C 3 -C 6 -cycloalkyl, or
(iii) a C 3 -C 8 cycloalkyl ring,
R 2 represents hydrogen, halogen, cyano, —C(O)OR 11 , —C(O)OH, or C 1 -C 6 -alkoxy,
R 3 represents C 1 -C 6 -alkyl,
R 4 represents hydrogen, SO 2 R 11 or —C(O)OR 11 ,
X represents —NH—,
Y represents —O— or —NH—,
A represents a bond, phenyl, or monocyclic heteroaryl ring,
n represents 1-4,
R 6 represents hydrogen,
R 7 and R 8 each represent C 1 -C 6 -alkyl,
R 11 represents C 1 -C 6 -alkyl or phenyl, which in each case is optionally substituted by nitro.
13. A process for the preparation of a compound according to claim 1 , comprising
eacting an intermediate compound according to formula (II) with a compound of the formula R 1 —XH to obtain a compound according to formula I, where R 4 is not hydrogen.
14. A process according to claim 13 , further comprising replacing the R 4 group with hydrogen for the preparation of compounds with R 4 equal to hydrogen, characterized by subsequent removal of R 4 unequal to hydrogen.
15. A pharmaceutical composition comprising a compound according to claim 1 and at least one galenic excipient selected from vehicles, fillers, disintegrants, binders, moisturizers, lubricants, absorbents and adsorbents, diluents, solvents, cosolvents, emulsifiers, solubilizers, taste corrigents, colorants, preservatives, stabilizers, wetting agents, salts for changing the osmotic pressure, and buffers.
16. A compound according to claim 1 , wherein
R 1 is an aryl or heteroaryl ring, which in each case is optionally substituted by hydroxyl, or is C 1 -C 6 -alkyl radical or C 3 -C 8 cycloalkyl which in each case is optionally mono- or polysubstituted by —NR 7 R 8 or C 1 -C 6 -alkoxy,
R 2 is hydrogen, halogen, —C(O)OR 11 , —C(O)OH or C 1 -C 6 -alkoxy,
R 3 is C 1 -C 3 -alkyl radical
R 4 is hydrogen, —SO 2 R 11 , or —C(O)OR 11 ,
X is —NH—,
Y is —O—,
A is a bond or an aryl ring,
n is 1-4,
R 7 and R 8 are each independently of one another C 1 -C 6 -alkyl,
R 11 is C 1 -C 3 -alkyl or an aryl ring, which in each case is optionally substituted by nitro.
17. A compound according to claim 1 , wherein R 9 and R 10 , independently of one another, is hydrogen or C 1 -C 6 -alkyl, which in each case is optionally mono- or polysubstituted by hydroxyl.
18. A compound according to claim 1 , wherein R 11 is C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, a C 3 -C 8 -cycloalkyl, aryl ring, a heterocyclyl ring having 3 to 8 ring atoms, or a heteroaryl ring, which in each case is optionally mono- or polysubstituted by hydroxyl, halogen, cyano, nitro, —NR 7 R 8 , C 1 -C 6 -alkyl , —CF 3 , C 1 -C 6 -alkoxy, and/or —OCF 3 .
19. A compound according to claim 1 , wherein said compound is selected from:
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]—N-(ethoxycarbonyl)-S-ethylsulphoximide,
(RS-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S -{3-[({6-Bromo-4-[(cyclopropylmethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(cyclopropylmethyl)amino]quinazolin-7-yl}oxy)methyl]phenyl}-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(4-hydroxyphenyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(1H-pyrazol-3-ylamino)quinazolin-7-yl]oxy}methyl)-phenyl]—N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(1H-pyrazol-3-ylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(2-methoxyethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-N-(ethoxycarbonyl)-S-ethylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(2-methoxyethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-(dimethylamino)ethyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-(dimethylamino)ethyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclobutylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclobutylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
Ethyl 7-({(RS)-3-[N-(ethoxycarbonyl)-S-methylsulphonimidoyl]benzyl}oxy)-4-(isopropylamino)quinazoline-6-carboxylate,
4-(Isopropylamino)-7-{[(RS)-3-(S -methylsulphonimidoyl)benzyl]oxy}-quinazoline-6-carboxylic acid,
(RS)-S-[3({[6-Bromo-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(4-pyridylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(4-pyridylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(3-pyridylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3({[6-Methoxy-4-(3-pyridylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(thiazol-2-ylamino)-chinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(thiazol-2-yl-amino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-ethylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-ethylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-ethylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-ethylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-ethyl-S-[3-({[6-methoxy-4-(thiazol-2-ylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-Ethyl-S-[3-({[6-methoxy-4-(thiazol-2-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-Ethyl-S [3-({[6-methoxy-4-(1H-pyrazol-3-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-Ethyl—S [3-({[6-methoxy-4-(oxazo-3-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(oxazo-3-ylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}quinazolin-7-yl)oxy]methyl}phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}quinazolin-7-yl)oxy]methyl}phenyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(2-hydroxyethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(2-hydroxyethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[4-({[6-methoxy-4-(3-pyridylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[4-({[6-Methoxy-4-(3-pyridylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[4-({[6-methoxy-4-(1,3,4-thiadiazol-2-yl-amino)quinazolin-7-yl]oxy}ethyl)phenyl]sulphoximide,
(RS)-S-[4-({[6-Methoxy-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(3-pyridylamino)quinazolin-7-yl]-amino}methyl)phenyl]sulphoximide,
(RS)-S-Methyl-S-[3-({[4-(3-pyridylamino)quinazolin-7-yl]amino}methyl)phenyl]-sulphoximide,
(RS)-S-[3-({[4-(Isopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-Methyl-S-[3-({[4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]amino}-methyl)phenyl]sulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(thiazol-2-ylamino)quinazolin-7-yl]-amino}methyl)phenyl]sulphoximide,
(RS)-S-Methyl-S-[3-({[4-(thiazol-2-ylamino)quinazolin-7-yl]amino}methyl)-phenyl]sulphoximide,
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(2-methyl-5-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[4-(2-Methyl-5-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({4-[(3-Cyanophenyl)amino]-6-methoxyquinazolin-7-yl}oxy)methyl]phenyl}-N -(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-{3-[({4-[(3-Cyanophenyl)amino]-6-methoxyquinazolin-7-yl}oxy)methyl]phenyl}-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(2-methyl-4-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[4-(2-Methyl-4-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
N-{2-[(6-Bromo-7-{3-[(RS)-N-(ethoxycarbonyl)-S-methylsulphonimidoyl]-benzyloxy}quinazolin-4-yl)amino]ethyl}acetamide,
N-{2-[(6-Bromo-7-{3-[(RS)-S-methylsulphonimidoyl]benzyloxy}quinazolin-4-yl)-amino]ethyl}acetamide,
(RS)-S-[3-({[6-Bromo-4-(ethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(ethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(3-hydroxy-2,2-dimethylpropyl)amino]quinazolin-7-yl}-oxy)methyl]phenyl}-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(RS)-2-hydroxy-1-methylethyl]amino}quinazolin-7-yl)-oxy]methyl}phenyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(S)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4- {[(R)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(R)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]methyl}-phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(R)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-S-methylsulphoximide,
and pharmaceutically acceptable salts thereof.
20. A compound according to claim 1 , wherein said compound is selected from:
(RS)-N-(Ethoxycarbonyl)-S-[3-({[4-(isopropylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methyl-sulphoximide,
Ethyl 7-({(RS)-3-[N-(ethoxycarbonyl)-S-methylsulphonimidoyl]benzyl}oxy)-4-(thiazol-2-ylamino)quinazoline-6-carboxylate,
Ethyl 7-{[(RS)-3-(S-methylsulphonimidoyl)benzyl]oxy}-4-(thiazol-2-ylamino)-quinazoline-6-carboxylate,
(RS)-N-(Ethoxycarbonyl)-S-[3-({[4-(isopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Isopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[4-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[4-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-ethyl-S-[3-({[4-(isopropylamino)-6-methoxyquinaz olin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-Ethyl-S-[3-({[4-(isopropylamino)-6-methoxyquinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Cyano-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxyc arb onyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Cyano-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
and pharmaceutically acceptable salts thereof.
21. A compound according to claim 1 , wherein said compound is selected from:
(RS)-S-(4-{[4-(Isopropylamino)-6-methoxyquinazolin-7-yl]oxy}butyl)-S-methyl-N-[(4-nitrophenyl)sulphonyl]sulphoximide,
(RS)-S-(4-{[4-(Isopropylamino)-6-methoxyquinazolin-7-yl]oxy}butyl)-S-methyl-sulphoximide,
(RS)-S-(4-{[4-(Isopropylamino)-6-methoxyquinazolin-7-yl]oxy}propyl)-S-methyl-N-[(4-nitrophenyl)sulphonyl]sulphoximide,
(RS)-S-(4-{[4-(Isopropylamino)-6-methoxyquinazolin-7-yl]oxy}propyl)-S-methyl-sulphoximide,
Ethyl 4-(isopropylamino)-7-[(RS)-3-{S-methyl-N-[(4-nitrophenyl)sulphonyl]-sulphonimidoyl}propoxy]quinazoline-6-carboxylate,
Ethyl 4-(isopropylamino)-7-[(RS)-3-(S-methylsulphonimidoyl)propoxy]-quinazoline-6-carboxylate,
(RS)-S-[4-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)pyridin-3-yl]-S-methylsulphoximide,
and pharmaceutically acceptable salts thereof.
22. A compound according to claim 19 , wherein said compound is selected from:
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(cyclopropylmethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(cyclopropylmethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(4-hydroxyphenyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(1H-pyrazol-3-ylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(1H-pyrazol-3-ylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(2-methoxyethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(2-methoxyethyl)amino]quinazolin-7-yl}oxy)methyl]-phenyl}-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-(dimethylamino)ethyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-(dimethylamino)ethyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclopropylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclobutylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(cyclobutylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}quinazolin-7-yl)oxy]methyl}phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}quinazolin-7-yl)oxy]methyl}phenyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(2-hydroxyethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(2-hydroxyethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(isopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-S-methylsulphoximide,
N-{2-[(6-Bromo-7-{3-[(RS)-N-(ethoxycarbonyl)-S-methylsulphonimidoyl]-benzyloxy}quinazolin-4-yl)amino]ethyl}acetamide,
N-{2-[(6-Bromo-7-{3-[(RS)-S-methylsulphonimidoyl]benzyloxy}quinazolin-4-yl)-amino]ethyl}acetamide,
(RS)-S-[3-({[6-Bromo-4-(ethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[6-Bromo-4-(ethylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({6-Bromo-4-[(3-hydroxy-2,2-dimethylpropyl)amino]quinazolin-7-yl}-oxy)methyl]phenyl}-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(RS)-2-hydroxy-1-methylethyl]amino}quinazolin-7-yl)-oxy]methyl}phenyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(S)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]methyl}phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(S)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(R)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]methyl}-phenyl)-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-(3-{[(6-Bromo-4-{[(R)-2-hydroxypropyl]amino}quinazolin-7-yl)oxy]-methyl}phenyl)-S-methylsulphoximide,
and pharmaceutically acceptable salts thereof.
23. A compound according to claim 19 , wherein said compound is selected from:
Ethyl 7-({(RS)-3-[N-(ethoxycarbonyl)-S-methylsulphonimidoyl]benzyl}oxy)-4-(isopropylamino)quinazoline-6-carboxylate,
4-(Isopropylamino)-7-{[(RS)-3-(S-methylsulphonimidoyl)benzyl]oxy}-quinazoline-6-carboxylic acid,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(4-pyridylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(4-pyridylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(3-pyridylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(3-pyridylamino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(thiazol-2-ylamino)-chinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(thiazol-2-yl-amino)quinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[6-methoxy-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-ethylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-ethylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-N-(ethoxycarbonyl)-S-ethylsulphoximide,
(RS)-S-[3-({[4-(Cyclobutylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]-S-ethylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-ethyl-S-[3-({[6-methoxy-4-(thiazol-2-ylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-Ethyl-S-[3-({[6-methoxy-4-(thiazol-2-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-Ethyl-S-[3-({[6-methoxy-4-(1H-pyrazol-3-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-Ethyl-S-[3-({[6-methoxy-4-(oxazo-3-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]sulphoximide,
(RS)-S-[3-({[6-Methoxy-4-(oxazo-3-ylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[4-({[6-methoxy-4-(3-pyridylamino)-quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[4-({[6-methoxy-4-(3-pyridylamino)quinazolin-7-yl]oxy}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[4-({[6-methoxy-4-(1,3,4-thiadiazol-2-yl-amino)quinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[4-({[6-Methoxy-4-(1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]oxy}-methyl)phenyl]-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-[3-({[4-(Cyclopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(3-pyridylamino)quinazolin-7-yl]-amino}methyl)phenyl]sulphoximide,
(RS)-S-Methyl-S-[3-({[4-(3-pyridylamino)quinazolin-7-yl]amino}methyl)phenyl]-sulphoximide,
(RS)-S-[3-({[4-(Isopropylamino)quinazolin-7-yl]amino}methyl)phenyl]-S-methylsulphoximide,
(RS)-S-Methyl-S-[3-({[4-({1,3,4-thiadiazol-2-ylamino)quinazolin-7-yl]amino}-methyl)phenyl]sulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(thiazol-2-ylamino)quinazolin-7-yl]-amino}methyl)phenyl]sulphoximide,
(RS)-S-Methyl-S-[3-({[4-(thiazol-2-ylamino)quinazolin-7-yl]amino}methyl)-phenyl]sulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(2-methyl-5-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[4-(2-Methyl-5-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
(RS)-S-{3-[({4-[(3-Cyanophenyl)amino]-6-methoxyquinazolin-7-yl}oxy)methyl]phenyl}-N-(ethoxycarbonyl)-S-methylsulphoximide,
(RS)-S-{3-[({4-[(3-Cyanophenyl)amino]-6-methoxyquinazolin-7-yl}oxy)methyl]phenyl}-S-methylsulphoximide,
(RS)-N-(Ethoxycarbonyl)-S-methyl-S-[3-({[4-(2-methyl-4-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)phenyl]sulphoximide,
(RS)-S-[3-({[4-(2-Methyl-4-pyridylamino)-6-methoxyquinazolin-7-yl]oxy}methyl)-phenyl]-S-methylsulphoximide,
and pharmaceutically acceptable salts thereof.