Solid forms of pharmaceutically acceptable salts of (S)-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(3-hydroxypyrrolidin-1-yl)methanone as JAK inhibitors
View Patent ↗The present disclosure relates to a JAK inhibitor compound and uses thereof. Specifically, the present disclosure discloses a compound of formula (G) in a solid form, isotopically labeled compound thereof, or optical isomer thereof, geometric isomer thereof, a tautomer thereof or a mixture of various isomers, or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a metabolite thereof. The present disclosure also relates to the application of the compound in a solid form in medicine.
1 . A crystal form of a pharmaceutically acceptable salt of a compound of formula (I):
wherein the crystal form of the pharmaceutically acceptable salt of the compound of formula (I) is selected from the group consisting of:
(1) the crystal form A of the benzenesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 5.82°±0.10°, 6.74°±0.10°, 11.85°±0.10°, and 16.38°±0.10°;
(2) the crystal form B of the benzenesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.93°±0.10°, 5.63°±0.10°, 9.02°±0.10°, 10.89°±0.10°, 14.84°±0.10°, 17.55°±0.10°, 18.84°±0.10°, 23.12°±0.10°, 25.55°±0.10°, and 26.14°±0.10°;
(3) the crystal form A of the citrate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.85°±0.10°, 6.42°±0.10°, 14.63°±0.10°, 17.12°±0.10°, 20.75°±0.10°, and 25.34°±0.10°;
(4) the crystal form B of the citrate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.96°±0.10°, 7.67°±0.10°, 10.20°±0.10°, 11.04°±0.10°, 14.73°±0.10°, 19.23°±0.10°, 22.86°±0.10°, 23.54°±0.10°, 24.28°±0.10°, and 25.08°±0.10°;
(5) the crystal form A of the fumarate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.96°±0.10°, 7.66°±0.10°, 10.21°±0.10°, 11.06°±0.10°, 14.74°±0.10°, 16.11°±0.10°, 22.87°±0.10°, and 25.10°±0.10°;
(6) the crystal form A of the hydrochloride salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 8.05°±0.10°, 17.11°±0.10°, 18.02°±0.10°, 20.84°±0.10°, 21.09°±0.10°, 22.77°±0.10°, and 23.14°±0.10°;
(7) the crystal form A of the maleate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.55°±0.10°, 8.78°±0.10°, 12.69°±0.10°, 13.96°±0.10°, 16.62°=0.10°, 17.61°±0.10°, 18.32°±0.10°, 25.39°±0.10°, and 26.53°±0.10°;
(8) the crystal form B of the methanesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (°20) selected from the group consisting of 5.91°±0.10°, 9.22°±0.10°, 15.83°±0.10°, 17.73°±0.10°, 19.02°±0.10°, and 25.01°±0.10°;
(9) the crystal form A of the mucolate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.98°±0.10°, 10.22°±0.10°, 11.07°±0.10°, 14.75°±0.10°, 14.94°±0.10°, 16.13°±0.10°, 19.65°±0.10°, and 30.79°±0.10°;
(10) the crystal form A of the phosphate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 5.29°±0.10°, 7.47°±0.10°, 10.61°±0.10°, 19.16°±0.10°, and 21.32°±0.10°;
(11) the crystal form A of the tartrate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 7.90°±0.10°, 8.69°±0.10°, 13.12°±0.10°, 13.43°±0.10°, 18.11°=0.10°, 21.28°±0.10°, and 22.90°±0.10°; and
(12) the crystal form A of the p-toluenesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (°20) selected from the group consisting of 5.90°±0.10°, 9.34°±0.10°, 14.87°±0.10°, 15.33°±0.10°, 17.88°±0.10°, 18.76°±0.10°, 19.71°±0.10°, and 24.26°±0.10°.
2 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the benzenesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 5.82°±0.10°, 6.74°±0.10°, 11.85°±0.10°, and 16.38°±0.10°.
3 . The crystal form according to claim 2 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 19.46°±0.10° and 20.20°±0.10°.
4 . The crystal form according to claim 1 , wherein the crystal form is crystal form B of the benzenesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.93°±0.10°, 5.63°±0.10°, 9.02°±0.10°, 10.89°±0.10°, 14.84°±0.10°, 17.55°±0.10°, 18.84°±0.10°, 23.12°±0.10°, 25.55°±0.10°, and 26.14°±0.10°.
5 . The crystal form according to claim 4 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 10.30°±0.10°, 11.43°±0.10°, 14.23°±0.10°, 17.04°±0.10°, 19.66°±0.10°, 20.24°±0.10°, 22.71°±0.10°, and 24.91°±0.10°.
6 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the citrate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.85°±0.10°, 6.42°±0.10°, 14.63°±0.10°, 17.12°±0.10°, 20.75°±0.10°, and 25.34°±0.10°.
7 . The crystal form according to claim 6 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 7.64°±0.10°, 15.40°±0.10°, 18.12°±0.10°, 18.84°±0.10°, and 19.37°±0.10°.
8 . The crystal form according to claim 1 , wherein the crystal form is crystal form B of the citrate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.96°±0.10°, 7.67°±0.10°, 10.20°±0.10°, 11.04°±0.10°, 14.73°±0.10°, 19.23°±0.10°, 22.86°±0.10°, 23.54°±0.10°, 24.28°±0.10°, and 25.08°±0.10°.
9 . The crystal form according to claim 8 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 12.42°±0.10°, 16.09°±0.10°, 17.55°±0.10°, and 27.91°±0.10°.
10 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the fumarate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.96°±0.10°, 7.66°±0.10°, 10.21°±0.10°, 11.06°±0.10°, 14.74°±0.10°, 16.11°±0.10°, 22.87°±0.10°, and 25.10°±0.10°.
11 . The crystal form according to claim 10 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 12.44°±0.10°, 19.25°±0.10°, 23.54°±0.10°, 24.27°±0.10°, and 25.37°±0.10°.
12 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the hydrochloride salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 8.05°±0.10°, 17.11°±0.10°, 18.02°±0.10°, 20.84°±0.10°, 21.09°±0.10°, 22.77°±0.10°, and 23.14°±0.10°.
13 . The crystal form according to claim 12 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 15.04°±0.10°, 20.44°±0.10°, and 22.07°±0.10°.
14 . The crystal form according to claim 1 , wherein the crystal form A of the maleate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 4.55°±0.10°, 8.78°±0.10°, 12.69°±0.10°, 13.96°±0.10°, 16.62°±0.10°, 17.61°±0.10°, 18.32°±0.10°, 25.39°±0.10°, and 26.53°±0.10°.
15 . The crystal form according to claim 14 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 13.74°±0.10° and 21.72°±0.10°.
16 . The crystal form according to claim 1 , wherein the crystal form is crystal form B of the methanesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 5.91°±0.10°, 9.22°±0.10°, 15.83°±0.10°, 17.73°±0.10°, 19.02°±0.10°, and 25.01°±0.10°.
17 . The crystal form according to claim 16 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 20.61°±0.10°, 21.36°±0.10°, and 23.18°±0.10°.
18 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the mucolate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (2θ) selected from the group consisting of 4.98°±0.10°, 10.22°±0.10°, 11.07°±0.10°, 14.75°±0.10°, 14.94°±0.10°, 16.13°±0.10°, 19.65°±0.10°, and 30.79°=0.10°.
19 . The crystal form according to claim 18 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 7.69°±0.10°, 21.51°±0.10°, and 22.92°±0.10°.
20 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the phosphate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 5.29°±0.10°, 7.47°±0.10°, 10.61°±0.10°, 19.16°±0.10°, and 21.32°±0.10°.
21 . The crystal form according to claim 20 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 15.94°±0.10°, 16.77°±0.10°, 18.68°±0.10°, and 25.36°±0.10°.
22 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the tartrate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 7.90°±0.10°, 8.69°±0.10°, 13.12°±0.10°, 13.43°±0.10°, 18.11°±0.10°, 21.28°±0.10°, and 22.90°±0.10°.
23 . The crystal form according to claim 22 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 15.08°±0.10°, 17.17°±0.10°, 17.44°±0.10°, 19.40°±0.10°, 20.74°±0.10°, 24.15°±0.10°, and 24.95°±0.10°.
24 . The crystal form according to claim 1 , wherein the crystal form is crystal form A of the p-toluenesulfonate salt of the compound of formula (I) characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 5.90°±0.10°, 9.34°±0.10°, 14.87°±0.10°, 15.33°±0.10°, 17.88°±0.10°, 18.76°±0.10°, 19.71°±0.10°, and 24.26°±0.10°.
25 . The crystal form according to claim 24 , wherein the crystal form is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least one additional characteristic peak at a diffraction angle (° 2θ) selected from the group consisting of 12.99°±0.10°, 16.10°±0.10°, 19.34°±0.10°, 20.39°=0.10°, and 24.99°±0.10°.
26 . A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier, adjuvant, or excipient and the crystal form according to claim 1 .
27 . The pharmaceutical composition according to claim 26 , wherein the pharmaceutical composition is formulated as a dispersion.
28 . The pharmaceutical composition according to claim 27 , wherein the dispersion comprises a pharmaceutically acceptable medium.
29 . The pharmaceutical composition according to claim 28 , wherein the pharmaceutically acceptable medium disperses the crystal form.
30 . The pharmaceutical composition according to claim 26 , wherein the pharmaceutical composition is formulated as a solution.
31 . The pharmaceutical composition according to claim 30 , wherein the solution comprises a pharmaceutically acceptable solvent.
32 . The pharmaceutical composition according to claim 31 , wherein the pharmaceutically acceptable solvent dissolves the crystal form.