6-pyrimidin-isoindole derivative as ERK1/2 inhibitor
AssigneeOtsuka Pharmaceutical Co., Ltd.
InventorsMichael Reader, Nicola Elizabeth Wilsher, Mark Henry Saunders, Paul Anthony Baguley, Colin Thomas Lindley, Robert Craig Melling, Bozena Ewa Adamczyk, Mirka Scarati
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Abstract
This invention relates to the compound (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide, and in particular to novel physical forms of the compound, a process for preparing the compound and synthetic intermediates for use in the process, and novel formulations containing the compound, as well as therapeutic uses of the compound.
Claims26
(2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide, having the formula (1):
- or a tautomeric form thereof, in a substantially crystalline form.
A process for making (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide, which process comprises:
- a) reacting a compound of formula (5):
- with a compound of formula (6)
- to give a compound of formula (2):
- and:
- b) reacting the compound of formula (2) with a compound of formula (3):
- to give the compound of formula (1):
- and thereafter optionally forming a salt or crystalline form thereof.
A pharmaceutical composition comprising (2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide and a vehicle selected from:
- a C2-4 alcohol;
- a polyether compound;
- mono-esters of C8 to C18 long chain fatty acids with glycerol or propylene glycol;
- di- or tri-glycerides of C8 to C10 long chain fatty acids;
- and mixtures thereof;
- and optionally a non-ionic surfactant.
(2R)-2-(6-{5-chloro-2-[(oxan-4-yl)amino]pyrimidin-4-yl}-1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]propanamide in the form of particles having a mass median diameter of between 1 μm and 100 μm.
Dependencies are inferred from the claim text.