[1,2,4]triazolo[4,3-b]pyridazines for use in the treatment of proliferative diseases

Patent metadata

Field	Value
Publication number	US-11407755-B2
Application number	US-202016930911-A
Country	US
Kind code	B2
Filing date	Jul 16, 2020
Priority date	Jul 28, 2014
Publication date	Aug 9, 2022
Grant date	Aug 9, 2022

Abstract

The invention concerns compounds of Formula (I)

or pharmaceutically-acceptable salts thereof, wherein R 1 , R 2 and n have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use as anti-proliferative and/or cell-killing agents.

First claim

The invention claimed is:

1. A co-crystal of a compound of Formula (IA):

and a co-former molecule 6-hydroxy-2-naphthoic acid, wherein the compound of Formula (IA) and the co-former molecule are in a molar ratio of 1:0.8 to 1:1.2.

2. The co-crystal of claim 1 , which has a degree of crystallinity greater than about 90%.

3. The co-crystal of claim 2 , which has a degree of crystallinity greater than about 95%.

4. The co-crystal of claim 1 , wherein the compound of Formula (IA) and the co-former molecule are in a molar ratio of 1:1.

5. The co-crystal of claim 1 , which is in a crystalline form (Form A) having a XRPD pattern with at least two specific peaks at 2-theta=19.4° and 12.5° plus or minus 0.2° 2-theta, measured using CuKα radiation.

6. The co-crystal of claim 5 , wherein the crystalline form (Form A) has a XRPD pattern with specific peaks at about 2-theta=19.4, 12.5, 12.8, 18.1, 24.2, 23.4, 14.0, 18.6, 17.0, and 17.9° plus or minus 0.2° 2-theta, measured using CuKα radiation.

7. The co-crystal of claim 5 , wherein the crystalline form (Form A) has a XRPD pattern substantially the same as the XRPD pattern shown in Figure I, measured using CuKα radiation.

8. The co-crystal of claim 1 , which is in a crystalline form (Form B) having a XRPD pattern with at least two specific peaks at 2-theta=15.2° and 6.1° plus or minus 0.2° 2-theta, measured using CuKα radiation.

9. The co-crystal of claim 8 , wherein the crystalline form (Form B) has a XRPD pattern with specific peaks at about 2-theta=15.2, 6.1, 16.8, 12.2, 26.1, 28.4, 18.3, 3.1 and 20.7° plus or minus 0.2° 2-theta, measured using CuKα radiation.

10. The co-crystal of claim 8 , wherein the crystalline form (Form B) has a XRPD pattern substantially the same as the XRPD pattern shown in Figure K, measured using CuKα radiation.

11. The co-crystal of claim 1 , which is in a crystalline form (Form C) having a XRPD pattern with at least two specific peaks at 2-theta=8.2° and 24.8° plus or minus 0.2° 2-theta, measured using CuKα radiation.

12. The co-crystal of claim 11 , wherein the crystalline form (Form C) has a XRPD pattern with specific peaks at about 2-theta=8.2, 24.8, 18.9, 29.0, 14.8, 15.5 and 16.3° plus or minus 0.2° 2-theta, measured using CuKα radiation.

13. The co-crystal of claim 11 , wherein the crystalline form (Form C) has a XRPD pattern substantially the same as the XRPD pattern shown in Figure M, measured using CuKα radiation.

14. A pharmaceutical composition comprising a co-crystal of claim 1 and a pharmaceutically acceptable carrier.

15. A method of treating cancer in a warm-blooded animal in need thereof, comprising administering to the warm-blooded animal an effective amount of a co-crystal of claim 1 or a pharmaceutical composition thereof, wherein the cancer is ovarian cancer, acute myeloid and mixed lineage leukemia (AML), multiple myeloma (MM), and diffuse large B-cell lymphoma (DLBCL).

Assignees

• Astrazeneca Ab

Inventors

• Bradbury Robert Hugh
• Rabow Alfred Arthur
• Waring Michael James
• Mccabe James Francis
• Glossop Steven Christopher
• Mahmood Arshed
• Cotter Zoe Ann

Classifications

• E21B7/062

  the tool shaft rotating inside a non-rotating guide travelling with the shaft (E21B7/067 and E21B7/068 take precedence) · CPC title

• E21B7/06

  Deflecting the direction of boreholes · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title