Patent
Disclosed is a hemisulfate salt of Compound (I): and crystalline forms of the hemisulfate salt. Also disclosed are methods of using the hemisulfate salt of Compound (I) as a CGRP receptor antagonist, and pharmaceutical compositions comprising the hemisulfate salt of Compound (I). The hemisulfate salt of Compound (I) is useful in treating, preventing, or ameliorating disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).
1. A hemisulfate salt of Compound (I):
2. The hemisulfate salt of Compound (I) according to claim 1 , wherein said salt of Compound (I) is crystalline.
3. The hemisulfate salt of Compound (I) according to claim 1 , wherein said salt Compound (I) is a sesquihydrate.
4. The hemisulfate salt of Compound (I) according to claim 3 , wherein said salt comprises crystalline Form H1.5-1.
5. The hemisulfate salt of Compound (I) according to claim 4 , wherein said Form H1.5-1 is characterized by one or more of the following:
a) unit cell parameters substantially equal to the following:
Cell dimensions: a=10.92 Å
b=33.04 Å
c=7.90 Å
α=90 degrees
β=90 degrees
γ=90 degrees
Space group: P2 1 2 1 2
Molecules of Compound (I)/asymmetric unit: I
Volume=2851 Å 3
Density (calculated)=1.423 g/cm 3 ,
wherein measurement of said crystalline form is at a temperature of about 25° C.;
b) an observed powder x-ray diffraction pattern substantially in accordance with the pattern shown in FIG. 1 ;
c) a simulated powder x-ray diffraction pattern substantially in accordance with the pattern shown in FIG. 1 ;
d) a powder x-ray diffraction pattern (CuKα λ=1.5418 Å) comprising four or more 2θ values selected from: 5.4±0.1, 8.6±0.1, 9.7±0.1, 12.4±0.1, 14.9±0.1, 17.6±0.1, 18.1±0.1, 20.5±0.1, 21.4±0.1, and 22.0±0.1, wherein measurement of the crystalline form is at a temperature of about 25° C.;
and/or
e) a solid state nuclear resonance spectra comprising six or more peaks ( (ppm) referenced to TMS) selected from: 26.6±0.1, 27.1±0.1, 28.3±0.1, 30.7±0.1, 43.1±0.1, 45.9±0.1, 47.1±0.1, 52.0±0.1, 54.2±0.1, 72.5±0.1, 117.0±0.1, 117.7±0.1, 124.2±0.1, 125.2±0.1, 128.3±0.1, 130.3±0.1, 131.4±0.1, 134.1±0.1, 140.8±0.1, 144.7±0.1, 148.7±0.1, 149.8±0.1, 151.2±0.1, 153.4±0.1, 155.1±0.1, 155.6±0.1, and 156.7±0.1.
6. A pharmaceutical composition comprising said hemisulfate salt of Compound (I) according to claim 1 ; and a pharmaceutically acceptable carrier of diluent.
7. The pharmaceutical composition according to claim 6 , wherein said hemisulfate salt of Compound (I) is a sesquihydrate.
8. The pharmaceutical composition according to claim 7 , wherein said hemisulfate salt of Compound (I) comprises crystalline Form H1.5-1.