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US 12,527,797 B2Granted
Isochromene derivatives as phosphoinositide 3-kinases inhibitors
AssigneeChiesi Farmaceutici S.p.A.
InventorsMatteo Biagetti, Paolo Ronchi, Claudio Fiorelli, Paolo Bruno
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Abstract
The invention relates to compounds of formula (I) inhibiting phosphoinositide 3-kinases (PI3K), to pharmaceutical compositions comprising them and therapeutic use thereof in the treatment of disorders associated with PI3K enzymes.
Claims16
A compound of formula (I):
- wherein:
- each R, when present, is independently selected from the group consisting of:
- OR7, halogen, and (C1-C6) alkyl;
- R1 and R2 taken together with the nitrogen atom they are linked to, form a 4-methylpiperazine-1-yl group;
- R3 and R4 are H;
- R5 is OR7;
- R6 is selected from the group consisting of:
- H, OR7, (C1-C6) alkyl, (C1-C6) haloalkyl, and (C1-C6) hydroxyalkyl;
- R7 is selected from the group consisting of:
- H and (C1-C6) alkyl;
- and
- p is zero or an integer ranging from 1 to 4;
- or a pharmaceutically acceptable salt of said compound.
10 more elements
A compound selected from the group consisting of:
- 3-{1-[4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl}-4-{3-[(4-methylpiperazin-1-yl)methyl]phenyl}-1H-isochromen-1-one;
- 3-(1-(4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((dimethylamino)methyl)phenyl)-1H-isochromen-1-one;
- 3-{1-[4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl}-4-{4-chloro-3-[(dimethylamino)methyl]phenyl}-1H-isochromen-1-one;
- 3-{1-[4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl}-4-{3-[(2R)-1-methylpyrrolidin-2-yl]phenyl}-1H-isochromen-1-one;
- 3-{1-[4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl}-4-{4-fluoro-3-[(4-methylpiperazin-1-yl)methyl]phenyl}-1H-isochromen-1-one;
- 3-(1-(4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-fluoro-5-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one;
- and
- 3-(1-(4-Amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(1-(dimethylamino) ethyl)phenyl)-1H-isochromen-1-one,
- or a pharmaceutically acceptable salt of said compound.
6 more elements
A compound selected from the group consisting of:
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Hydrobromide;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Hydrochloride;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Hemi 1,5-Naphthalenedisulfonate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Hemisulfate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Tosylate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Mesylate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one 2-Naphthalene sulfonate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Isethionate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Maleate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Esylate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Hemipamoate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Xinafoate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Salycilate;
- (R) and/or(S)-3-(1-(4-amino-3-(5-hydroxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-isochromen-1-one Benzoate,
- or a pharmaceutically acceptable salt of said compound.
12 more elements
Dependencies are inferred from the claim text.