Solid state forms of mnk inhibitors
Assignees4E Therapeutics, Inc., Board of Regents, The University of Texas System
InventorsTheodore J. Price, James J. Sahn, Daniel Rixson, Osama Suleiman, Arlindo Lucas Castelhano, Garry Robert Smith
Life of this patent
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Abstract
The present disclosure relates to solid forms of a compound having the following Structure (I): or a tautomer thereof. The present disclosure is also directed to methods of making and using a compound of Structure (I).
Claims41
A solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the solid form has an X-ray powder diffraction pattern with at least two peaks at 2-theta angles selected from the group consisting of 5.6±0.2°, 10.9±0.2°, 18.2±0.2°, and 18.6±0.2°.
A solid form of a compound having the following Structure (I):
- or a tautomer thereof, having an X-ray powder diffraction pattern substantially in accordance with that depicted in FIG. 1.
A solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the solid form is prepared by a process comprising steps of:
- (i) providing N-(6-((8″-methyl-1″,5″-dioxo-1″,5″-dihydro-2″H-dispiro[cyclopropane-1,1′-cyclohexane-4′,3″-imidazo[1,5-a]pyridin]-6″-yl)amino)pyrimidin-4-yl)cyclopropanecarboxamide (Int-A);
- (ii) contacting Int-A with a hydroxide base (e.g., potassium hydroxide) in a suitable solvent (e.g., ethanol, tetrahydrofuran, and water, or a mixture thereof);
- and
- (iii) isolating the solid form of a compound having Structure (I).
A solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the solid form has an X-ray powder diffraction pattern with at least two peaks at 2-theta angles selected from the group consisting of 19.2±0.2°, 19.5±0.2°, and 21.2±0.2°.
A solid form of a compound having the following Structure (I):
- or a tautomer thereof, having an X-ray powder diffraction pattern substantially in accordance with that depicted in FIG. 3.
A solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the solid form is prepared by a process comprising steps of:
- (i) providing Structure (I) Pattern 3;
- (ii) heating Structure (I) Pattern 3 to about 250° C. under vacuum;
- and
- (iii) isolating the solid form of a compound having Structure (I).
An amorphous solid form of a compound having the following Structure (I):
- or a tautomer thereof.
An amorphous solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the amorphous form is prepared by a process comprising steps of:
- (i) providing Structure (I) Pattern 3;
- (ii) ball milling Structure (I) Pattern 3 at a suitable frequency (e.g., 30 Hz) and for a suitable amount of time (e.g., 3 sessions of 90 min each);
- and
- (iii) isolating the amorphous form of a compound having Structure (I).
A crystalline solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the crystalline solid form is described in the Example herein.
A crystalline solid form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the crystalline solid form is prepared by a process comprising steps of:
- (i) providing Structure (I);
- (ii) contacting Structure (I) with one or more suitable solvents (e.g., n-heptane, ethyl acetate, isopropyl acetate, methyl isobutyl ketone, 2-propanol, methyl ethyl ketone, acetone, ethanol, tert-butyl methyl ether, 2-methyl-1-propanol, cyclohexane, methanol, toluene, tetrahydrofuran, acetonitrile, water, dimethylsulfoxide, or a combination thereof);
- and
- (iii) isolating the crystalline solid form,
- the process optionally comprising a step of heating or cooling the mixture of Structure (I) in a suitable solvent or a solid precipitate isolated therefrom.
A salt form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the salt form is formed between Structure (I) and a co-former selected from hydrochloric acid, hydrobromic acid, sulfuric acid, acetic acid, maleic acid, fumaric acid, phosphoric acid, citric acid, p-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, tartaric acid, succinic acid, and malic acid.
A salt form of a compound having the following Structure (I):
- or a tautomer thereof, wherein the salt form is prepared by a process comprising steps of:
- (i) providing Structure (I);
- (ii) contacting Structure (I) with a co-former selected from hydrochloric acid, hydrobromic acid, sulfuric acid, acetic acid, maleic acid, fumaric acid, phosphoric acid, citric acid, p-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, tartaric acid, succinic acid, and malic acid;
- and
- (iii) isolating the salt form.
A solid form (e.g., a crystalline or amorphous form of a free base or salt form) of a compound having the following Structure (I):
- or a tautomer thereof, wherein the solid form is prepared by a process described in the Examples herein.
A method of preparing a solid form of a compound having the following Structure (I):
- or a tautomer thereof, the method comprising steps of:
- (i) providing N-(6-((8″-methyl-1″,5″-dioxo-1″,5″-dihydro-2″H-dispiro[cyclopropane-1,1′-cyclohexane-4′,3″-imidazo[1,5-a]pyridin]-6″-yl)amino)pyrimidin-4-yl)cyclopropanecarboxamide (Int-A);
- (ii) contacting Int-A with a hydroxide base (e.g., potassium hydroxide) in a suitable solvent (e.g., ethanol, tetrahydrofuran, and water, or a mixture thereof);
- and
- (iii) isolating the solid form of a compound having Structure (I).
A method of preparing a solid form of a compound having the following Structure (I):
- or a tautomer thereof, the method comprising steps of:
- (i) providing Structure (I) Pattern 3;
- (ii) heating Structure (I) Pattern 3 to about 250° C. under vacuum;
- and
- (iii) isolating the solid form of a compound having Structure (I).
A method of preparing an amorphous form of a compound having the following Structure (I):
- or a tautomer thereof, the method comprising steps of:
- (i) providing Structure (I) Pattern 3;
- (ii) ball milling Structure (I) Pattern 3 at a suitable frequency (e.g., 30 Hz) and for a suitable amount of time (e.g., 3 sessions of 90 min each);
- and
- (iii) isolating the amorphous form of a compound having Structure (I).
A method of preparing a crystalline solid form of a compound having the following Structure (I):
- or a tautomer thereof, the method comprising steps of:
- (i) providing Structure (I);
- (ii) contacting Structure (I) with one or more suitable solvents (e.g., n-heptane, ethyl acetate, isopropyl acetate, methyl isobutyl ketone, 2-propanol, methyl ethyl ketone, acetone, ethanol, tert-butyl methyl ether, 2-methyl-1-propanol, cyclohexane, methanol, toluene, tetrahydrofuran, acetonitrile, water, dimethylsulfoxide, or a combination thereof);
- and
- (iii) isolating the crystalline solid form,
- the method optionally comprising a step of heating or cooling the mixture of Structure (I) in a suitable solvent or a solid precipitate isolated therefrom.
A method of preparing a salt form of a compound having the following Structure (I):
- or a tautomer thereof, the method comprising steps of:
- (i) providing Structure (I);
- (ii) contacting Structure (I) with a co-former selected from hydrochloric acid, hydrobromic acid, sulfuric acid, acetic acid, maleic acid, fumaric acid, phosphoric acid, citric acid, p-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, tartaric acid, succinic acid, and malic acid;
- and
- (iii) isolating the salt form.
Dependencies are inferred from the claim text.