Polymorphs of (1S,2S,3S,5R)-3-((6-(Difluoromethyl)-5-Fluoro-1,2,3,4-Tetrahydroisoquinolin-8-YL)OXY)-5-(4-Methyl-7H-Pyrrolo[2,3-D]Pyrimidin-7-YL)Cyclopentane-1,2-DIOL Mono-Hydrochloride
This invention relates to crystalline mono-HCl salt forms of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, and to compositions and therapeutic uses thereof.
1 . A crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol.
2 . The A crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol of claim 1 characterized by a PXRD pattern measured using Cu K-alpha radiation comprising one or more peaks at about 11.0, 11.4 and 17.1 degrees 2-theta (+/−0.2 degrees 2-theta).
3 . The A crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol of claim 1 characterized by a PXRD pattern measured using Cu K-alpha radiation comprising one or more peaks at about 8.4, 11.0, 11.4 and 17.1 degrees 2-theta (+/−0.2 degrees 2-theta).
4 . The A crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol of claim 1 characterized by a PXRD pattern measured using Cu K-alpha radiation comprising one or more peaks at about 11.0, 11.4, 15.0 and 17.1 degrees 2-theta (+/−0.2 degrees 2-theta).
5 . The A crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol of claim 1 characterized by a PXRD pattern measured using Cu K-alpha radiation comprising peaks at about 8.4, 11.0, 11.4, 15.0 and 17.1 degrees 2-theta (+/−0.2 degrees 2-theta).
6 . (canceled)
7 . The A pharmaceutical composition comprising a crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol as claimed in claim 1 and a pharmaceutically acceptable carrier or excipient.
8 . A crystalline mono-HCl salt of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol as claimed in claim 1 , or a composition thereof as claimed in claim 7 , for use as a medicament.
9 . A crystalline mono HCl salt form of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol as claimed in claim 1 , or a composition thereof as claimed in claim 7 , for use in the treatment of abnormal cell growth in a mammal.
10 . (canceled)
11 . A method of treatment of abnormal cell growth in a mammal comprising administering to the mammal a therapeutically effective amount of a crystalline mono-HCl salt form of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol as claimed in claim 1 .
12 . (canceled)
13 . A combination of a crystalline mono-HCl salt form of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7- yl)cyclopentane-1,2-diol as claimed in claim 1 , with another anti-cancer agent.