Isethionate salt of a selective CDK4 inhibitor
View Patent ↗Disclosed are polymorphs of the isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.
1. An isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one comprising a mono-isethionate salt of Form A, characterized by one or more of the following: a powder X-ray diffraction pattern having peaks at 2θ values of about 8.7, 13.5, and 17.6, or a Raman spectrum having peaks at Raman Shift values of about 1600 cm −1 , 1290 cm −1 , 675 cm −1 , 470 cm −1 , 450 cm −1 , and 425 cm −1 , or a DSC thermogram having a sharp endotherm at about 273° C.
2. An isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one comprising a mono-isethionate salt of Form B, characterized by one or more of the following: a powder X-ray diffraction pattern having peaks at 2θ values of about 5.1, 11.8, 12.1, 12.8, 13.1, and 14.7, a Raman spectrum having peaks at Raman Shift values of about 1600 cm −1 , 1290 cm −1 , 470 cm −1 , 450 cm −1 , and 425 cm −1 , but no substantial peak at 675 cm −1 , or a DSC thermogram having a sharp endotherm at about 271° C.
3. An isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one comprising a mono-isethionate salt of Form D, characterized by one or more of the following: a powder X-ray diffraction pattern having peaks at 2θ values of about 8.4, 8.9, and 21.9, a Raman spectrum having a peak at a Raman Shift value of about 463 cm −1 , or a DSC thermogram having a sharp endotherm at about 277° C.
4. A pharmaceutical dosage form comprising an isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one according to any one of claims 1 to 3 and one or more pharmaceutically acceptable excipients.