Salt of ABT-263 and solid-state forms thereof
ABT-263 bis-HCl and crystalline polymorphs thereof are suitable active pharmaceutical ingredients for pharmaceutical compositions useful in treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.
1. The compound N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R1-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino-3-((trifluoromethyl)sulfonyl)benzenesulfonamide bis-hydrochloride (ABT-263 bis-HCl) in crystalline polymorph Form I thereof, characterized at least by a powder X-ray diffraction peak at any one or more of the following positions: 6.8, 7.2, 8.5, 18.5 and 18.7° 2θ, ±0.2° 2θ.
2. The crystalline polymorph of claim 1 , characterized at least by a powder X-ray diffraction peak at each of said positions.
3. The crystalline polymorph of claim 1 , characterized by a powder X-ray diffraction pattern substantially as indicated in the following table:
Peak Position (°2θ)
Relative Intensity
6.8
59.0
7.2
75.9
8.5
14.3
9.3
4.3
11.2
6.5
13.8
15.8
14.0
17.7
14.9
9.5
16.7
17.5
17.5
15.7
18.2
52.2
18.5
100.0
18.7
95.4.
4. The compound of N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino-3-((trifluoromethyl)sulfonyl)benzenesulfonamide bis-hydrochloride (ABT-263 bis-HCl) in crystalline polymorph Form II thereof, characterized at least by a powder X-ray diffraction peak at 3.7 or 7.4° 2θ, ±0.2° 2θ.
5. The crystalline polymorph of claim 4 , characterized at least by a powder X-ray diffraction peak at both 3.7 and 7.4° 2θ, ±0.2° 2θ.
6. The crystalline polymorph of claim 4 , characterized by a powder X-ray diffraction pattern substantially as indicated in the following table:
Peak position (°2θ)
Relative intensity
3.7
6.0
7.4
100.0
12.1
5.3
15.6
8.6
16.1
16.2
16.6
21.6
18.3
70.2
19.0
13.4.
7. A crystalline solvate comprising N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino-3-((trifluoromethyl)sulfonyl)benzenesulfonamide bis-hydrochloride (ABT-263 bis-HCl) solvated with an organic solvent.
8. The solvate of claim 7 , wherein the organic solvent is selected from the group consisting of ethanol, 1-propanol, 2-propanol, 2-butanol, t-butanol, nitromethane, acetonitrile, propionitrile, ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, methyl isopropyl ketone, 1,4-dioxane, benzene, toluene and butyl ether.
9. A pharmaceutical composition comprising crystalline polymorph Form I of ABT-263 bis-HCl and one or more pharmaceutically acceptable excipients.
10. A pharmaceutical composition comprising crystalline polymorph Form II of ABT-263 bis-HCl and one or more pharmaceutically acceptable excipients.