Solid state forms of (s)-2-(((s)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-n-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1h-imidazol-4-yl)pentanamide and uses thereof

Patent metadata

Field	Value
Publication number	US-2023087828-A1
Application number	US-202218049073-A
Country	US
Kind code	A1
Filing date	Oct 24, 2022
Priority date	Aug 9, 2019
Publication date	Mar 23, 2023
Grant date	—

Abstract

The present disclosure relates to: a) solid state forms of hydrobromide salts of Compound 1; b) pharmaceutical compositions comprising one or more solid state forms of hydrobromide salts of Compound 1, and, optionally, a pharmaceutically acceptable carrier; c) methods of treating tumors or cancers by administering one or more solid state forms of hydrobromide salts of Compound 1 to a subject in need thereof, and d) methods for the preparation of solid state forms of Compound 1.

First claim

1 - 144 . (canceled)

145 . A pharmaceutical composition comprising solid form of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide of Formula (I)

wherein the solid form has a D[V,0.90] particle size of about 100 μm.

146 . The pharmaceutical composition of claim 145 , wherein the (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide has a D[V,0.10] particle size of about 0.5 μm.

147 . The pharmaceutical composition of claim 145 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.

148 . The pharmaceutical composition of claim 145 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide and provides a Tmax of more than about 1 hour.

149 . The pharmaceutical composition of claim 148 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide and provides an in vivo area under the plasma curve (AUC inf ) of less than 700 ng h/ml

150 . The pharmaceutical composition of claim 146 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.

151 . The pharmaceutical composition of claim 146 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide and provides a Tmax of more than about 1 hour.

152 . The pharmaceutical composition of claim 151 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide and provides a an in vivo area under the plasma curve (AUC inf ) of less than 700 ng h/ml

153 . A pharmaceutical composition of (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide of Formula (I)

the solid form having a D[V,0.10] particle size between about 0.5 μm and about 15 μm, a D[V,0.50] particle size between about 2 μm and about 30 μm, a D[V,0.90] particle size between about 8 μm and about 600 μm, or a D[4,3] particle size of about 5 μm to about 200 μm.

154 . The pharmaceutical composition of claim 153 , having two or more of: a D[V,0.10] particle size between about 0.5 μm and about 15 μm, a D[V,0.50] particle size between about 2 μm and about 30 μm, a D[V,0.90] particle size between about 8 μm and about 600 μm, and a D[4,3] particle size of about 5 μm to about 200 μm.

155 . The pharmaceutical composition of claim 154 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide.

156 . The pharmaceutical composition of claim 153 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide and provides a Tmax of more than about 1 hour.

157 . The pharmaceutical composition of claim 156 , wherein the composition comprises about 50 mg (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl)pentanamide and provides a an in vivo area under the plasma curve (AUC inf ) of less than 700 ng h/ml.

Assignees

• Springworks Therapeutics Inc

Inventors

• Cheng Shinta
• Shearer Todd Webster
• Williams Rex
• Patterson Kristin

Classifications

• C07D233/88 Primary

  Nitrogen atoms, e.g. allantoin · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title