Crystalline 2,5-dione-3-(1-methyl-1h-indol-3-yl)-4-[1-(pyridin-2ylmethyl)piperidin-4-yl]-1h- pyrrole mono-hydrochloride

• US 20050288332A1
• Filed: 07/08/2003
• Published: 12/29/2005
• Est. Priority Date: 07/12/2002
• Status: Active Grant

• Current Assignee: Denovo Biopharma LLC
• Original Assignee: Eli Lilly and Company
• Inventors: Bush, Julie Kay, Faul, Margaret Mary, Reutzel-Edens, Susan Marie
• Granted Patent: US 8,114,901 B2
• Time in Patent Office: Days
• US Class Current: 514/332
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/14 containing three or more hetero rings

Abstract

The present invention relates to crystalline 2,5-dione-3-(1-methyl-1H-indol-3-yl)-4-[1-(pyridin-2-yl-methyl)piperidin-4-yl]-1H-indol-3-yl]-1H-pyrrole mono-hydrochloride salt, a pharmaceutical formulation containing said salt and to methods for treating cancer and for inhibiting tumor growth using said salt.

Claims

1. Crystalline 2,5-dione-3-(1-methyl-1H-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl]-1H-pyrrole mono-hydrochloride, a hydrate thereof, or mixtures thereof.

4. A pharmaceutical composition comprising a salt of claim 1 and a pharmaceutical carrier.

5. A method of treating non-Hodgkins lymphoma which comprises administering to a mammal in need thereof an effective amount of a compound of claim 1.

6. A method of treating glioblastoma which comprises administering to a mammal in need thereof an effective amount of a compound of claim 1.

7. A method of treating non-small cell lung cancer which comprises administering to a mammal in need thereof an effective amount of a compound of claim 1.

2. Crystalline 2,5-dione-3-(1-methyl-1H-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl]-1H-pyrrole mono-hydrochloride, a hydrate thereof, or mixtures thereof, having an X-ray diffraction pattern which comprises the following peaks:

6.8±

0.1, 10.9±

0.1, 14.2±

0.1 and 16.6±

0.1°

in 2θ

;

when the pattern is obtained from a copper radiation source (CuKα

;

λ

=1.54056 Å

).

3. The crystalline mono-hydrochloride of claim 2 having an X-ray diffraction pattern which further comprises the following peaks:

6.3±

0.1, 7.2±

0.1, 12.5±

0.1 and 17.0±

0.1°

in 2θ

.

15. A pharmaceutical composition comprising a salt of claim 2 and a pharmaceutical carrier.

16. A pharmaceutical composition comprising a salt of claim 3 and a pharmaceutical carrier.

17. A method of treating non-Hodgkins lymphoma which comprises administering to a mammal in need thereof an effective amount of a compound of claim 2.

18. A method of treating non-Hodgkins lymphoma which comprises administering to a mammal in need thereof an effective amount of a compound of claim 3.

19. A method of treating glioblastoma which comprises administering to a mammal in need thereof an effective amount of a compound of claim 2.

20. A method of treating glioblastoma which comprises administering to a mammal in need thereof an effective amount of a compound of claim 3.

21. A method of treating non-small cell lung cancer which comprises administering to a mammal in need thereof an effective amount of a compound of claim 2.

22. A method of treating non-small cell lung cancer which comprises administering to a mammal in need thereof an effective amount of a compound of claim 3.

8-14. -14. (canceled)