Chemical compounds
The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3-kinase activity.
1. A compound of formula (I):
wherein
R 1 is C 1-6 alkoxy or —N(C 1-6 alkyl) 2 ;
R 2 is hydrogen or C 1-6 alkyl optionally substituted by —C(O)OC 1-6 alkyl or —OC(O)C 1-6 alkyl;
R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen and halogen;
R 7 and R 8 are each independently C 1-6 alkyl, or
R 7 and R 8 , together with the nitrogen atom to which they are attached, are linked to form a 5- or 6-membered heterocyclyl wherein the 5- or 6-membered heterocyclyl optionally contains a further nitrogen atom and is optionally substituted by C 3-6 cycloalkyl, 4- to 6-membered heterocyclyl containing one or two heteroatoms independently selected from oxygen and nitrogen, or C 1-6 alkyl wherein the C 1-6 alkyl is optionally substituted by hydroxy or C 1-6 alkoxy, or
R 7 and R 8 , together with the nitrogen atom to which they are attached, are linked to form a 5- or 6-membered heterocyclyl wherein the 5- or 6-membered heterocyclyl contains an oxygen atom and is optionally substituted by one or two substituents independently selected from C 1-6 alkyl; or a salt thereof.
2. A compound according to claim 1 , or a salt thereof, wherein R 1 is C 1-6 alkoxy.
3. A compound according to claim 1 , or a salt thereof, wherein R 2 is hydrogen.
4. A compound according to claim 1 , or a salt thereof, wherein R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen and fluoro.
5. A compound according to claim 1 , or a salt thereof, wherein R 7 and R 8 , together with the nitrogen atom to which they are attached, are linked to form a 5- or 6-membered heterocyclyl wherein the 5- or 6-membered heterocyclyl optionally contains a further nitrogen atom and is optionally substituted by C 3-6 cycloalkyl, 4- to 6-membered heterocyclyl containing one or two heteroatoms independently selected from oxygen and nitrogen, or C 1-6 alkyl wherein the C 1-6 alkyl is optionally substituted by hydroxy or C 1-6 alkoxy.
6. A compound which is:
N-(2-(2-fluoro-4((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-(tert-butyl)piperazin-1-yl)methyl)-2-fluorophenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((dimethylamino)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(3-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-(tert-butyl)piperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-cyclobutylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2,6-difluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-(sec-butyl)piperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(3,5-difluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
2-methoxy-5-morpholino-N-(2-(4-((4-(oxetan-3-yl)piperazin-1-yl)methyl)phenyl)pyridin-4-yl)pyridine-3-sulfonamide;
N-(2-(2,3-difluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((4-(oxetan-3-yl)piperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-cyclobutylpiperazin-1-yl)methyl)-2-fluorophenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2,5-difluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((4-(2-methoxyethyl)piperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((3-methylpyrrolidin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4((2-methylpyrrolidin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-(piperidin-1-ylmethyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-(((cis)-2,6-dimethylmorpholino)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
2-methoxy-5-morpholino-N-(2-(4-(morpholinomethyl)phenyl)pyridin-4-yl)pyridine-3-sulfonamide;
N-(2-(2-fluoro-4-(piperazin-1-ylmethyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
2-(dimethylamino)-N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-(tert-butyl)piperazin-1-yl)methyl)-2-fluorophenyl)pyridin-4-yl)-2-(dimethylamino)-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-((4-(tert-butyl)piperazin-1-yl)methyl)-2-fluorophenyl)pyridin-4-yl)-2-methoxy-N-methyl-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-N-methyl-5-morpholinopyridine-3-sulfonamide;
N-ethyl-N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholino-N-propylpyridine-3-sulfonamide;
N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-N-isopropyl-2-methoxy-5-morpholinopyridine-3-sulfonamide;
ethyl 2-(N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamido)acetate;
(N-(2-(2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamido)methyl pivalate; or
N-(2-(5-chloro-2-fluoro-4-((4-isopropylpiperazin-1-yl)methyl)phenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-(((2S,6R)-2,6-dimethylmorpholino)methyl)-2-fluorophenyl)pyridin-4-yl)-2-methoxy-5-morpholinopyridine-3-sulfonamide;
N-(2-(4-(((2S,6R)-2,6-dimethylmorpholino)methyl)-2-fluorophenyl)pyridin-4-yl)-2-ethoxy-5-morpholinopyridine-3-sulfonamide; or a salt thereof.
7. A compound which is:
or a salt thereof.
8. A compound according to claim 1 in the form of a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.