Patent ID: 8674108
Filing Date: 2014-03-18
Classification: A61K,A61P,C07D

Abstract:
1. A crystalline solvate of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), wherein the crystalline solvate is designated as a solid form selected from the group consisting of Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form K, Form L, Form M, Form N, Form O, Form P, Form Q, Form R, Form S, Form T, Form W, and Hydrate B, wherein Form D is an acetonitrile solvate, or an acetonitrile/water 75/25 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 5.6±0.2 degrees, 6.0±0.2 degrees, 7.8±0.2 degrees, 13.5±0.2 degrees, 14.1±0.2 degrees, 14.7±0.2 degrees, and 16.2±0.2 degrees; Form E is a methylethyl ketone (MEK) solvate, a MEK/water 99/1 solvate, a MEK/water 90/10 solvate, or a MEK/water 80/20 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 8.0±0.2 degrees, 8.6±0.2 degrees, 10.1±0.2 degrees, 11.0±0.2 degrees, 11.9±0.2 degrees, 16.5±0.2 degrees, 17.1±0.2 degrees, and 18.1±0.2 degrees; Form F is an acetonitrile/water 75/25 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 7.2±0.2 degrees, 7.8±0.2 degrees, 9.4±0.2 degrees, 10.7±0.2 degrees, 12.1±0.2 degrees, 12.8±0.2 degrees, 14.1+0.2 degrees, and 14.7±0.2 degrees; Form G is an isopropyl acetate solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 6.3±0.2 degrees, 7.3±0.2 degrees, and 12.4±0.2 degrees; Form H is an isopropyl acetate/water 95/5 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 7.9±0.2 degrees, 9.9±0.2 degrees, 10.4±0.2 degrees, 11.6±0.2 degrees, 12.1±0.2 degrees, 14.8±0.2 degrees, 16.0±0.2 degrees, and 17.9±0.2 degrees; Form I is a MEK solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 6.8±0.2 degrees, 8.4±0.2 degrees, 9.4±0.2 degrees, 10.2±0.2 degrees, 11.4±0.2 degrees, 17.1±0.2 degrees, 17.8±0.2 degrees, and 18.3±0.2 degrees; Form J is a MEK/water 99/1 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 6.0±0.2 degrees, 7.9±0.2 degrees, 8.8±0.2 degrees, 9.9±0.2 degrees, 11.8±0.2 degrees, 17.7±0.2 degrees, 18.0±0.2 degrees, and 18.5±0.2 degrees; Form K is a methylethyl ketone (MEK) solvate, a MEK/water 99/1 solvate, a MEK/water 90/10 solvate, or a MEK/water 80/20 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 8.0±0.2 degrees, 8.5±0.2 degrees, 10.0±0.2 degrees, 11.8±0.2 degrees, 15.4±0.2 degrees, 15.9±0.2 degrees, 16.9±0.2 degrees, and 18.0±0.2 degrees; Form L is an isopropyl acetate/water 95/5 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 7.9±0.2 degrees, 10.4±0.2 degrees, 10.9±0.2 degrees, 12.1±0.2 degrees, 14.8±0.2 degrees, 16.0±0.2 degrees, 18.6±0.2 degrees, and 20.5±0.2 degrees; Form M is a methylethyl ketone (MEK) solvate or a MEK/water 99/1 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 5.2±0.2 degrees, 6.0±0.2 degrees, 6.9±0.2 degrees, 10.7±0.2 degrees, 12.3±0.2 degrees, 17.6±0.2 degrees, 18.3±0.2 degrees, and 21.1±0.2 degrees; Form N is a MEK/water 90/10 solvate or a MEK/water 80/20 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 8.2±0.2 degrees, 9.7±0.2 degrees, 10.6±0.2 degrees, 11.5±0.2 degrees, 12.4±0.2 degrees, 16.6±0.2 degrees, 17.6+0.2 degrees, and 23.8±0.2 degrees; Form O is a methylethyl ketone (MEK) solvate, or a MEK/water 99/1 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 5.7±0.2 degrees, 8.5±0.2 degrees, 9.5±0.2 degrees, 11.4±0.2 degrees, 15.3±0.2 degrees, 17.2±0.2 degrees, 18.9±0.2 degrees, and 22.2±0.2 degrees; Form P is a MEK/water 90/10 solvate or a MEK/water 80/20 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 6.1±0.2 degrees, 7.4±0.2 degrees, 8.2±0.2 degrees, 9.1±0.2 degrees, 11.5±0.2 degrees, 12.3±0.2 degrees, 16.7±0.2 degrees, and 17.7±0.2 degrees; Form O is a MEK/water 80/20 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 6.3±0.2 degrees, 7.6±0.2 degrees, 8.4±0.2 degrees, 11.1±0.2 degrees, 12.5±0.2 degrees, 16.4±0.2 degrees, 16.9±0.2 degrees, and 18.0±0.2 degrees; Form R is an acetonitrile solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 6.7±0.2 degrees, 7.7±0.2 degrees, 13.2±0.2 degrees., 15.1±0.2 degrees, and 17.8±0.2 degrees; Form S is a MEK/water 80/20 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 4.8±0.2 degrees, 7.7±0.2 degrees, 8.2±0.2 degrees, 9.6±0.2 degrees, 11.6±0.2 degrees, 15.1±0.2 degrees, 18.3±0.2 degrees, and 23.6±0.2 degrees; Form T is an isopropyl acetate/water 95/5 solvate, and is characterized by the following peaks in an X-ray powder diffraction pattern: 4.9±0.2 degrees, 8.3±0.2 degrees, 9.8±0.2 degrees, 11.6±0.2 degrees, 18.1±0.2 degrees, 18.7±0.2 degrees, 21.1±0.2 degrees, and 24.0±0.2 degrees; Form W is a solvated form from 10% water/90% acetonitrile, and is characterized by the following peaks in an X-ray powder diffraction pattern: 5.5±0.2 degrees, 10.9±0.2 degrees, 12.1±0.2 degrees, 13.3±0.2 degrees, 14.6±0.2 degrees, 17.2±0.2 degrees, 18.8±0.2 degrees, and 21.8±0.2 degrees; and Hydrate B is a hydrated form of Compound 1, and is characterized by the following peaks in an X-ray powder diffraction pattern: 4.9±0.2 degrees, 6.0±0.2 degrees, 7.2±0.2 degrees, 8.9±0.2 degrees, 10.1±0.2 degrees, 10.7±0.2 degrees, 11.3±0.2 degrees, and 11.9±0.2 degrees, and wherein the peaks are measured on a 2θ scale.