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Machine translation
1. (WO2016123581) CRYSTALLINE C21H22C12N4O2 MALONATE
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

What is claimed is:

1 . A malonate salt of a compound of formula (I):


which is a crystalline salt.

2. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 3.0° 2Θ.

3. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at about 3.0 and 5.2° 2Θ.

4. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks selected from the group consisting of about 3.0, 5.2, 8.0, and 10.9° 2Θ.

5. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising XRPD 20-reflections (°) at about 3.0. 5.2, 8.0, 10.9, 15.7, 18.4, 23.1 , and 25.4.

6. A malonate salt of a compound of formula (I):


having an XRPD pattern substantially as shown in FIG. 7.

7. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having an infrared spectroscopy (IR) spectrum comprising one or more peaks at about 1573, 1504, 1475, 1253, 1033, and 883 cm"1.

8. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having an IR spectrum substantially as shown in FIG. 8.

9. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having (i) an XRPD pattern comprising one or more peaks at about 3.0. 5.2,

8.0, and 10.9° 2Θ; and (ii) an IR spectrum comprising one or more peaks at about 1573, 1504, 1475, 1253, 1033, and 883 cm"1.

10. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having a DSC thermogram with an endotherm having an onset temperature of approximately 142.1 °C.

1 1 . Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having a DSC thermogram substantially as shown in FIG. 9.

12. A pharmaceutical composition comprising a crystalline compound according to any one of claims 1 -1 1 and a pharmaceutically acceptable carrier.

13. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 1 -1 1 .

14. The method according to claim 13, wherein the subject is a mammal.

15. The method according to claim 14, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

16. The method according to claim 14, wherein the mammal is a human.

17. The method according to claim 13 further comprising administering to the subject at least one additional anti-cancer agent.

18. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 12.

19. The method according to claim 18, wherein the subject is a mammal.

20. The method according to claim 19, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

21. The method according to claim 19, wherein the mammal is a human.

22. The method according to claim 18 further comprising administering to the subject at least one additional anti-cancer agent.

23. A method of making Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate comprising reacting malonic acid and 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide under conditions suitable to form Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate.

24. The method according to claim 23, wherein the malonic acid and 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide are reacted in an ethanol slurry.

AMENDED CLAI MS

received by the International Bureau on

26 April 2016 (26.04.2016)

What is claimed is:

1 A malonate salt of a compound of formula (I):


characterized by an X-ray powder diffraction (XRPD) pattern comprising a characteristic peak at about 3.0° 2Θ, which is a crystalline salt.

3. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at about 3.0 and 5.2° 2Θ.

4. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising additional characteristic peaks selected from the group consisting of about 5.2, 8.0, and 10.9° 2Θ.

5. The malonate salt according to claim 1 characterized by an X-ray powder diffraction (XRPD) pattern comprising XRPD 20-reflections (°) at about 3.0. 5.2, 8.0, 10.9, 15.7, 18.4, 23.1 , and 25.4.

AMENDED SHEET (ARTICLE 19)

6. A malonate salt of a compound of formula (I):


having an XRPD pattern substantially as shown in FIG. 7.

7. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having an infrared spectroscopy (IR) spectrum comprising one or more peaks at about 1573, 1504, 1475, 1253, 1033, and 883 cm"1.

8. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having an IR spectrum substantially as shown in FIG. 8.

9. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having (i) an XRPD pattern comprising one or more peaks at about 3.0. 5.2, 8.0, and 10.9° 2Θ; and (ii) an IR spectrum comprising one or more peaks at about 1573, 1504, 1475, 1253, 1033, and 883 cm"1.

AMENDED SHEET (ARTICLE 19)

10. Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having a DSC thermogram with an endotherm having an onset temperature of approximately 142.1 °C.

1 1 . Form A crystalline 4-(5-Chloro-2-isopropylaminopyridin-4-yl)-1 H-pyrrole-2-carboxylic acid [1 -(3-chlorophenyl)-2-hydroxyethyl]amide malonate according to claim 1 having a DSC thermogram substantially as shown in FIG. 9.

12. A pharmaceutical composition comprising a crystalline compound according to any one of claims 1 -1 1 and a pharmaceutically acceptable carrier.

13. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a crystalline compound according to any one of claims 1 -1 1 .

14. The method according to claim 13, wherein the subject is a mammal.

15. The method according to claim 14, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

AMENDED SHEET (ARTICLE 19)

The method according to claim 14, wherein the mammal is a human.

17. The method according to claim 13 further comprising administering to the subject at least one additional anti-cancer agent.

18. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition according to claim 12.

19. The method according to claim 18, wherein the subject is a mammal.

20. The method according to claim 19, wherein the mammal is selected from the group consisting of humans, primates, farm animals, and domestic animals.

21 . The method according to claim 19, wherein the mammal is a human.

22. The method according to claim 18 further comprising administering to the subject at least one additional anti-cancer agent.

AMENDED SHEET (ARTICLE 19)