PIM KINASE INHIBITORS AS CANCER CHEMOTHERAPEUTICS
Inhibitors of Pim kinases, ways to make them and methods of treating patients using them are disclosed.
1 . A compound having formula I
or a salt thereof, wherein
A 1 and A 2 are independently selected H, R 1 , R 2 , R 3 , R 4 , OH, OR 5 , NH 2 , NHR 7 , N(R 7 ) 2 , F, Cl, Br or I;
R 1 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 2 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 3 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 4 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected heterocycloalkyl, CF 3 , F, Cl, Br or I;
R 5 is alkyl which is unsubstituted or substituted with one or two of independently selected R 6 , OH, OR 7 , NH 2 , NHR 7 or N(R 7 ) 2 ;
R 6 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 7 is H, R 8 , R 9 , R 10 or R 11 ;
R 8 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 9 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 10 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 11 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected heterocycloalkyl, CF 3 , F, Cl, Br or I; or
A 1 and A 2 are taken together with the atoms to which they are attached and are benzene, cycloalkane, heteroarene or heterocycloalkane, each of which is unfused or fused with benzene, heteroarene or heterocycloalkane;
A 3 is H, R 12 , R 13 , R 14 or R 15 ;
R 12 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 13 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 14 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 15 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , NHW 1 , N(W 1 ) 2 , phenyl, heteroaryl or heterocycloalkyl;
W 1 is phenyl, alkyl, alkenyl or alkynyl;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two of independently selected R 16 , OR 16 , SR 16 , S(O)R 16 , SO 2 R 16 , C(O)R 16 , CO(O)R 16 , OC(O)R 16 , OC(O)OR 16 , NH 2 , NHR 16 , N(R 16 ) 2 , C(O)NH 2 , C(O)NHR 16 , C(O)N(R 16 ) 2 , SO 2 NH 2 , SO 2 NHR 16 , SO 2 N(R 16 ) 2 , C(O)H, C(O)OH, OH, (O), N 3 , NO 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, Cl, Br or I; wherein
R 16 is H, R 17 , R 18 , R 19 or R 20 ;
R 17 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 18 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 19 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 20 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , NH(alkyl), N(alkyl) 2 or R 21 ;
R 21 is phenyl, heteroaryl or heterocycloalkyl, each of which is unfused or fused with benzene, heteroarene or heterocycloalkane;
and wherein the moieties represented by R 17 , R 18 , R 19 and R 21 are unsubstituted or substituted with OH, CN, F, Cl, Br or I.
2 . The compound of claim 1 wherein
A 1 and A 2 are independently selected H, R 1 , R 2 , R 3 , R 4 OH, OR 5 , NH 2 , NHR 7 , N(R 7 ) 2 , F, Cl, Br or I;
R 1 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 2 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 3 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 4 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected heterocycloalkyl, CF 3 , F, Cl, Br or I;
R 5 is alkyl which is unsubstituted or substituted with one or two of independently selected R 6 , OH, OR 7 , NH 2 , NHR 7 or N(R 7 ) 2 ;
R 6 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 7 is H, R 8 , R 9 , R 10 or R 11 ;
R 8 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 9 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 10 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 11 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected heterocycloalkyl, CF 3 , F, Cl, Br or I; or
A 1 and A 2 are taken together with the atoms to which they are attached and are benzene, cycloalkane, heteroarene or heterocycloalkane, each of which is unfused or fused with benzene, heteroarene or heterocycloalkane;
A 3 is H, R 12 , R 13 , R 14 or R 15 ;
R 12 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 13 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 14 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 15 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , NHW 1 , N(W 1 ) 2 , phenyl, heteroaryl or heterocycloalkyl;
W 1 is phenyl, alkyl, alkenyl or alkynyl;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two of independently selected R 16 , OR 16 , C(O)R 16 , CO(O)R 16 , NH 2 , OH, NO 2 , CF 3 , F, Cl, Br or I; wherein
R 16 is H, R 17 , R 18 , R 19 or R 20 ;
R 17 is phenyl which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 18 is heteroarene which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 19 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 20 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , NH(alkyl), N(alkyl) 2 or R 21 ;
R 21 is phenyl, heteroaryl or heterocycloalkyl, each of which is unfused or fused with benzene, heteroarene or heterocycloalkane;
and wherein the moieties represented by R 17 , R 18 , R 19 and R 21 are unsubstituted or substituted with OH, CN, F, Cl, Br or I.
3 . The compound of claim 2 wherein
A 1 and A 2 are independently selected H, R 1 , R 2 , R 3 , R 4 , OH, OR 5 , NH 2 , NHR 7 , N(R 7 ) 2 , F, Cl, Br or I;
R 1 is phenyl which is unfused or fused with heteroarene;
R 2 is heteroarene;
R 3 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene;
R 4 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected heterocycloalkyl, CF 3 , F, Cl, Br or I;
R 5 is alkyl which is unsubstituted or substituted with one or two of independently selected R 6 , OH, OR 7 , NH 2 , NHR 7 or N(R 7 ) 2 ;
R 6 is phenyl;
R 7 is H, R 8 , R 9 , R 10 or R 11 ;
R 8 is phenyl;
R 9 is heteroarene;
R 10 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
R 11 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected heterocycloalkyl, CF 3 , F, Cl, Br or I; or
A 1 and A 2 are taken together with the atoms to which they are attached and are benzene, cycloalkane, heteroarene or heterocycloalkane, each of which is unfused or fused with benzene;
A 3 is H, R 12 , R 13 , R 14 or R 15 ;
R 12 is phenyl;
R 13 is heteroarene;
R 14 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
R 15 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , NHW 1 , N(W 1 ) 2 , phenyl, heteroaryl or heterocycloalkyl;
W 1 is phenyl, alkyl, alkenyl or alkynyl;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two of independently selected R 16 , OR 16 , C(O)R 16 , CO(O)R 16 , NH 2 , OH, NO 2 , CF 3 , F, Cl, Br or I; wherein
R 16 is H, R 17 , R 18 , R 19 or R 20 ;
R 17 is phenyl;
R 18 is heteroarene;
R 19 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
R 20 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , NH(alkyl), N(alkyl) 2 or R 21 ;
R 21 is phenyl, heteroaryl or heterocycloalkyl;
and wherein the moieties represented by R 17 , R 18 , R 19 and R 21 are unsubstituted or substituted with OH, CN, F, Cl, Br or I.
4 . The compound of claim 3 wherein
A 1 and A 2 are independently selected H, R 1 , R 2 , R 3 , R 4 , F, Cl, Br or I;
R 1 is phenyl which is unfused or fused with heteroarene;
R 2 is heteroarene;
R 3 is heterocycloalkenyl, which is unfused or fused with benzene;
R 4 is alkyl;
A 1 and A 2 are taken together with the atoms to which they are attached and are benzene, cycloalkane, heteroarene or heterocycloalkane, each of which is unfused or fused with benzene;
A 3 is H, R 12 , or R 15 ;
R 12 is phenyl;
R 15 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NHW 1 , N(W 1 ) 2 , or heterocycloalkyl;
W 1 is phenyl or alkyl;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two of independently selected R 16 , OR 16 , C(O)R 16 , CO(O)R 16 , NH 2 , OH, NO 2 , CF 3 , F, Cl, Br or I; wherein
R 16 is H, R 17 , R 18 , R 19 or R 20 ;
R 17 is phenyl;
R 18 is heteroarene;
R 19 is heterocycloalkyl;
R 20 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two of independently selected NH 2 , N(alkyl) 2 or R 21 ;
R 21 is phenyl or heterocycloalkyl;
and wherein the moieties represented by R 17 are unsubstituted or substituted with OH, CN, F, Cl, Br or I.
5 . The compound of claim 1 which is
8-bromo-2-[(3-hydroxyphenylamino)methyl]-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
8-chloro-2-(2-piperidin-1-ylethyl)-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
2-dimethylaminomethyl-8-pyrrolidin-1-yl-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
2-dimethylaminomethyl-8-(4-hydroxyphenyl)-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
2-dimethylaminomethyl-8-((E)-pent-1-enyl)-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
2-((S)-3-hydroxypyrrolidin-1-ylmethyl)-8-thiophen-3-yl-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
2-dimethylaminomethyl-8-(6-piperidin-1-yl-hex-1-ynyl)-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
7-(1H-indol-5-yl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
7-(4-hydroxyphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-((dimethylamino)methyl)-6-phenyl-7-m-tolylthieno[3,2-d]pyrimidin-4(3H)-one;
(R)-7-bromo-2-((3-hydroxypyrrolidin-1-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
8-[(3-hydroxyphenylamino)methyl]-5,6,6b,10a-tetrahydro-9H-11-thia-7,9-diaza-benzo[a]fluoren-10-one;
9H-7-thia-9,11-diaza-benzo[c]fluoren-8-one;
9-(3-aminopropoxy)-3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one;
6-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
6-(4-fluorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
8,9-dichloro-2-(4-nitrophenyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8,9-dichloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-methyl-8-nitro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-bromo-9-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2,7,9-trimethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one;
1,3-dimethyl-1H-pyrazolo[4′,3′:4,5]thieno[3,2-d]pyrimidin-7(6H)-one;
6-bromothieno[3,2-d]pyrimidin-4(3H)-one;
7-bromothieno[3,2-d]pyrimidin-4(3H)-one;
6-(3-hydroxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
6-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(dimethylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-(piperidin-1-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-(morpholin-4-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-[3-(trifluoromethyl)phenyl]thieno[3,2-d]pyrimidin-4(3H)-one;
6-(3-aminophenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
9-methyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-(3-pyrrolidin-1-ylpropyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(4-hydroxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3-hydroxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-phenyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-(3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-(3-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
7-(4-chlorophenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
5,6-dihydronaphtho[2′,1′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
7-(3-hydroxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
7-(4-hydroxy-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
6-pyridin-3-ylthieno[3,2-d]pyrimidin-4(3H)-one;
2-(anilinomethyl)-8-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-vinyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-piperidin-1-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-fluoro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-nitro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-fluoro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-(trifluoromethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6,7-difluoro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-bromo[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-(trifluoromethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-(3-hydroxyphenyl)-7-methylthieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3-methoxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3-hydroxy-4-methoxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(4-hydroxypiperidin-1-yl)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}-8-(trifluoromethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-(piperidin-1-ylmethyl)-8-(trifluoromethyl) [1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(trifluoromethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-(morpholin-4-ylmethyl)-8-(trifluoromethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3,5-dihydroxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-(1H-pyrrol-1-yl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo-2-(morpholin-4-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo-2-[(dimethylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo-2-(piperidin-1-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-(4-piperidin-1-ylbutyl) [1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[3-(dimethylamino)propyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
5,6-dihydronaphtho[1′,2′:4,5]thieno[3,2-d]pyrimidin-8(9H)-one;
6-(4-hydroxy-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
9-bromo[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-{[(4-hydroxyphenyl)amino]methyl}-5,6-dihydronaphtho[2′,1′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
8-[(3-hydroxypiperidin-1-yl)methyl]-5,6-dihydronaphtho[2′,1′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
9-phenoxy[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-(4-hydroxyphenyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3-hydroxy-2-methylphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3-hydroxy-4-methylphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(2-hydroxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-(azepan-1-ylmethyl)-8-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(methylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[2-(dimethylamino)ethyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-pyridin-3-ylthieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(ethylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(propylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(isopropylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(pentylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(neopentylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3,3-dimethylbutyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-(2-morpholin-4-ylethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{2-[(3-hydroxyphenyl)amino]ethyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-(2-morpholin-4-ylethoxy)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
9-hydroxy[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-phenyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
3-methoxy-5,6-dihydronaphtho[2′,1′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
8-chloro-2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-(tetrahydropyrimidin-1(2H)-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-(1,4′-bipiperidin-1′-ylmethyl)-8-chloro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(3-hydroxypiperidin-1-yl)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-(piperidin-1-ylmethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(2,6-dimethylmorpholin-4-yl)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-{[(3R)-3-hydroxypiperidin-1-yl]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-vinyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-thien-3-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-phenyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-chloro-2-[(3,4-dihydroxypiperidin-1-yl)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-ethyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-methyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}-8-methyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one
6-tert-butyl-7-(3-hydroxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]thieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}thieno[3,2-d]pyrimidin-4(3H)-one;
7-bromo[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
3-(benzyloxy)-5,6-dihydronaphtho[2′,1′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
methyl 4-oxo-3,4-dihydro[1]benzothieno[3,2-d]pyrimidine-7-carboxylate;
7-(4-hydroxyphenyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-(3-hydroxyphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
6-(1H-pyrazol-5-yl)thieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-piperidin-1-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-(4-hydroxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
6-(2-hydroxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
7-hydroxy[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(3-fluorophenyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(3-furyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-(2-hydroxyphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
3-hydroxy-5,6-dihydronaphtho[2′,1′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
6H-chromeno[3′,4′:4,5]thieno[3,2-d]pyrimidin-10(9H)-one;
4-{2-[(dimethylamino)methyl]-4-oxo-3,4-dihydro[1]benzothieno[3,2-d]pyrimidin-8-yl}benzonitrile;
2-[(dimethylamino)methyl]-8-nitro[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-ethynyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-(1H-indol-2-yl)thieno[3,2-d]pyrimidin-4(3H)-one;
6-phenyl-7-(4-pyrrolidin-1-ylphenyl)thieno[3,2-d]pyrimidin-4(3H)-one;
7-bromo-2-[(dimethylamino)methyl]-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-7-(3-hydroxyphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-7-(4-hydroxyphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(3,3-dimethylbut-1-ynyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-pent-1-ynyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-(3-chlorophenyl)-2-[(dimethylamino)methyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}-8-thien-3-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(1-phenylethyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-isopropyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo-2-{[(4-fluoro-3-methoxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo-2-{[(4-fluoro-3-hydroxyphenyl)amino]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-bromo-2-{[(3-hydroxyphenyl)amino]methyl}-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
7-(4-hydroxyphenyl)-2-{[(3-hydroxyphenyl)amino]methyl}-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3-hydroxyphenyl)amino]methyl}-8-phenyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-bromo-2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}-8-thien-3-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
8-(4-hydroxyphenyl)-2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
4-(2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}-4-oxo-3,4-dihydro[1]benzothieno[3,2-d]pyrimidin-8-yl)benzonitrile;
8-(3-chloro-5-fluorophenyl)-2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}-8-phenyl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-[3-(dimethylamino)prop-1-ynyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
7-(4-acetylphenyl)-2-[(dimethylamino)methyl]-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-7-(4-methylphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-pyridin-3-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-pyrimidin-5-yl[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(1H-pyrrol-2-yl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(3-hydroxyphenyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(3-fluoro-4-hydroxyphenyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-7-(3-methylphenyl)-6-phenylthieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-[(1E)-1-methylprop-1-enyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-[(E)-2-phenylvinyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
2-[(dimethylamino)methyl]-8-(5-phenylpent-1-ynyl)[1]benzothieno[3,2-d]pyrimidin-4(3H)-one;
or a therapeutically acceptable salt thereof.