US2024043457A1PendingUtilityA1
Crystalline forms of 5-chloro-n4-[-2-(dimethylphosphoryl) phenyl]-n2-{2-methoxy-4-[4[(4-methylpiperazin-1-yl) piperidin-1-yl] phenyl} pyrimidine-2,4-diamine
Est. expiryOct 21, 2034(~8.2 yrs left)· nominal 20-yr term from priority
C07F 9/65583C07D 239/48C07B 2200/13C07D 401/12A61K 31/506A61P 11/00C07D 401/14A61P 35/00A61P 43/00C07F 9/025
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Claims
Abstract
Novel crystalline forms of brigatinib, pharmaceutical compositions comprising the same, and methods of their preparation and use of the same are disclosed herein.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . Crystalline brigatinib.
2 . Substantially pure crystalline brigatinib.
3 . Crystalline Form A of brigatinib.
4 . The crystalline Form A of claim 3 , wherein the crystalline Form A of brigatinib is substantially pure.
5 . The crystalline Form A of claim 3 or 4 having an x-ray powder diffraction pattern substantially as shown in FIG. 2 .
6 . The crystalline Form A of claim 3 or 4 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 6.1, 8.6, 9.6, 10.8, 11.3, 13.5, 14.3, 15.9, 17.2, 18.9, 19.4, 20.1, 21.8, 22.6, 23.1, 23.9, and 27.7.
7 . The crystalline Form A of claim 3 or 4 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 9.6, 17.2, 19.4, 20.1, 23.1, and 27.7.
8 . The crystalline Form A of any one of claims 3 - 7 , wherein the crystalline Form A is anhydrous.
9 . The crystalline Form A of any of one claims 3 - 7 having an onset melting temperature of 214.5° C.
10 . The crystalline Form A of any one of claims 3 - 7 having a FT-IR spectrum with any at least one of the following frequency bands:
Frequency (cm −1 )
3241.0, 3165.1
2980.0 to 2793.2
1616.4 to 1417.6
1441.1 to 1219.8
1354.6 to 1278.0
1307.4 to 1196.1
1163.6 to 1135.0
1094.9 to 794.6
867.4
768.6 to 716.8.
11 . A process for preparing crystalline Form A of brigatinib comprising elevating the temperature of crystallization to 60° C. and adding an NaOH solution at a slow rate.
12 . Crystalline Form B of brigatinib.
13 . The crystalline Form B of claim 14 , wherein the crystalline Form B of brigatinib is substantially pure.
14 . The crystalline Form B of claim 12 or 13 having an x-ray powder diffraction pattern substantially as shown in FIG. 14 .
15 . The crystalline Form B of claim 12 or 13 having an x-ray powder diffraction pattern with at least four peaks expressed in degrees two-theta chosen from 5.7, 9.2, 11.5, 12.8, 14.5, 15.5, 16.9, 17.7, 19.2, 20.4, 21.8, 23.2, and 29.5.
16 . The crystalline Form B of claim 12 or 13 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 11.5, 14.5, 16.9, 19.2 and 23.2.
17 . Crystalline Form C of brigatinib.
18 . The crystalline Form C of claim 17 , wherein the crystalline Form C of brigatinib is substantially pure.
19 . The crystalline Form C of claim 17 or 18 having an x-ray powder diffraction pattern substantially as shown in FIG. 18 .
20 . The crystalline Form C of claim 17 or 18 having an x-ray powder diffraction pattern with at least four peaks expressed in degrees two-theta chosen from 2.1, 2.5, 5.4, 9.9, 10.9, 12.9, 14.9, 15.9, 16.6, 17.3, 17.9, 19.2, 20.6, 23.9, 26.8, and 27.4.
21 . The crystalline Form C of claim 17 or 18 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 5.4, 14.9, 15.9, 17.3, 19.2, and 23.9.
22 . Crystalline Form D of brigatinib.
23 . The crystalline Form D of claim 22 , wherein the crystalline Form D of brigatinib is substantially pure.
24 . The crystalline Form D of claim 22 or 23 having an x-ray powder diffraction pattern substantially as shown in FIG. 19 .
25 . The crystalline Form D of claim 22 or 23 having an x-ray powder diffraction pattern with at least four peaks expressed in degrees two-theta chosen from 4.7, 9.2, 9.7, 11.1, 14.5, 17.4, 18.9, 22.4, and 23.7.
26 . The crystalline Form D of claim 22 or 23 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 9.7, 11.1, 17.4, 18.9, and 23.7.
27 . Crystalline Form E of brigatinib.
28 . The crystalline Form E of claim 27 , wherein the crystalline Form E of brigatinib is substantially pure.
29 . The crystalline Form E of claim 27 or 28 having an x-ray powder diffraction pattern substantially as shown in FIG. 21 .
30 . The crystalline Form E of claim 27 or 28 having an x-ray powder diffraction pattern with at least four peaks expressed in degrees two-theta chosen from 9.1, 10.2, 11.2, 12.0, 13.7, 14.4, 15.8, 16.5, 17.4, 18.3, 19.2, 21.6, 22.3, 23.1, 23.9, 26.0, 26.4, 25.8, and 29.3.
31 . The crystalline Form E of claim 27 or 28 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 9.1, 10.2, 15.8, 19.2, and 23.9.
32 . Crystalline Form F of brigatinib.
33 . The crystalline Form F of claim 32 , wherein the crystalline Form F of brigatinib is substantially pure.
34 . The crystalline Form F of claim 32 or 33 having an x-ray powder diffraction pattern substantially as shown in FIG. 23 .
35 . The crystalline Form F of claim 32 or 33 having an x-ray powder diffraction pattern with at least four peaks expressed in degrees two-theta chosen from 8.5, 9.8, 11.1, 16.3, 17.0, 17.6, 18.7, 19.4, 20.3, 22.0, 23.2, 23.9, and 27.1.
36 . The crystalline Form F of claim 32 or 33 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 9.8, 17.0, 19.4, 20.3 and 27.1.
37 . Crystalline Form G of brigatinib.
38 . The crystalline Form G of claim 37 , wherein the crystalline Form G of brigatinib is substantially pure.
39 . The crystalline Form G of claim 37 or 38 having an x-ray powder diffraction pattern substantially as shown in FIG. 24 .
40 . The crystalline Form G of claim 37 or 38 having an x-ray powder diffraction pattern with at least four peaks expressed in degrees two-theta chosen from 7.2, 8.3, 9.7, 10.4, 12.9, 15.8, 18.1, 18.7, 20.7, 21.5, 22.8, 23.5, 24.5, and 26.8.
41 . The crystalline Form G of claim 37 or 38 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 8.3, 9.7, 12.9, 15.8, 18.1, 20.7, 22.8, and 26.8.
42 . Crystalline Form H of brigatinib.
43 . The crystalline Form H of claim 42 , wherein the crystalline Form H of brigatinib is substantially pure.
44 . The crystalline Form H of claim 42 or 43 having an x-ray powder diffraction pattern substantially as shown in FIG. 25 .
45 . The crystalline Form H of claim 42 or 43 having an x-ray powder diffraction pattern with characteristic peaks expressed in degrees two-theta chosen from 4.2, 5.2, 8.4, 10.9, 12.7, 15.0, 15.7, 16.5, 17.2, 18.4, 19.5, and 21.3.
46 . The crystalline Form H of claim 42 or 43 having an x-ray powder diffraction pattern with at least two peaks expressed in degrees two-theta chosen from 4.2, 5.2, 8.4, 10.9, 12.7, and 21.3.
47 . A pharmaceutical composition comprising at least one crystalline form of brigatinib and at least component chosen from pharmaceutically acceptable carriers, pharmaceutically acceptable vehicles, and pharmaceutically acceptable excipients.
48 . The pharmaceutical composition of claim 47 , wherein the at least one crystalline form of brigatinib is substantially pure.
49 . The pharmaceutical composition of claim 47 or 48 , wherein the at least one crystalline form of brigatinib is chosen from Form A, Form B, Form C, Form D, Form E, Form F, Form G, and Form H.
50 . The pharmaceutical composition of claim 47 or 48 , wherein the crystalline brigatinib is Form A.
51 . A method for treating non-small cell lung cancer in a subject in need thereof comprising administering to the subject at least one crystalline form of brigatinib.
52 . The method of claim 51 , wherein the at least one crystalline form of brigatinib is substantially pure.
53 . The method of claim 51 or 52 , wherein the at least one crystalline form of brigatinib is chosen from Form A, Form B, Form C, Form D, Form E, Form F, Form G, and Form H.
54 . The method of claim 51 or 52 , wherein the at least one crystalline form of brigatinib is Form A.Join the waitlist — get patent alerts
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