JPWO2021091819A5

JPWO2021091819A5 -

Info

Publication number: JPWO2021091819A5
Application number: JP2022525923A
Authority: JP
Publication date: 2023-11-13

Claims

(E)-3-(4-((1R,3R)-2-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-2,3,4,9-tetrahydro-1H- Pyrido[3,4-b]indol-1-yl)-3,5-difluorophenyl)acrylic acid (compound A)

A pharmaceutically acceptable salt of
The pharmaceutically acceptable salt of Compound A is a hydrogen sulfate of Compound A.

A pharmaceutically acceptable salt of
The pharmaceutically acceptable salt of Compound A is a sulfate of Compound A.

and the sulfate salt of Compound A.

4. The pharmaceutically acceptable salt form of claim 3 , wherein the salt form is Form A.

Form A is characterized by one or more peaks in an X-ray powder diffraction pattern, the one or more peaks ranging from about 9.4 degrees 2θ to about 9.7 degrees 2θ, about 10.2 The pharmaceutically acceptable pharmaceutically acceptable compound of claim 4 is selected from a peak within a range of degrees 2θ to about 10.5 degrees 2θ, and a peak within a range of about 10.9 degrees 2θ to about 11.2 degrees 2θ. salt form.

4. The pharmaceutically acceptable salt form of claim 3 , wherein the salt form is Form C.

Form C is characterized by one or more peaks in an X-ray powder diffraction pattern, the one or more peaks being within the range of about 9.0 degrees 2θ to about 9.3 degrees 2θ, about 9.8 7. The pharmaceutically acceptable pharmaceutically acceptable compound of claim 6 selected from peaks within the range of degrees 2θ to about 10.1 degrees 2θ, and peaks within the range of about 14.1 degrees 2θ to about 14.4 degrees 2θ. salt form.

4. The pharmaceutically acceptable salt form of claim 3 , wherein the salt form is Form D.

Form D is characterized by one or more peaks in an X-ray powder diffraction pattern, the one or more peaks ranging from a peak within a range of about 6.2 degrees 2θ to about 6.6 degrees 2θ. 9. A peak within a range of about 9.3 degrees 2-theta to about 9.7 degrees 2 - theta, and a peak within a range of about 9.8 degrees 2-theta to about 10.2 degrees 2-theta. A pharmaceutically acceptable salt form of.

4. The pharmaceutically acceptable salt form of claim 3 , wherein the salt form is Form E.

Form E is characterized by one or more peaks in an X-ray powder diffraction pattern, the one or more peaks ranging from about 4.2 degrees 2θ to about 4.6 degrees 2θ, about 8.5 Peaks within the range of degrees 2θ to approximately 8.9 degrees 2θ, peaks within the range of approximately 9.7 degrees 2θ to approximately 10.1 degrees 2θ, and peaks within the range of approximately 11.7 degrees 2θ to approximately 12.1 degrees 2θ 11. A pharmaceutically acceptable salt form according to claim 10 , which may be selected from the peaks within.

A pharmaceutically acceptable salt of
Selected pharmaceutically acceptable salts include the HCl salt of Compound A, the citrate of Compound A, the mesylate of Compound A, the besylate of Compound A, the choline salt of Compound A, and the sulfur salt of Compound A. A pharmaceutically acceptable salt of Compound A selected from the group consisting of acid salts.

13. The pharmaceutically acceptable salt of claim 12 , wherein the HCl salt of Compound A has an X-ray powder diffraction pattern corresponding to the representative XRPD spectra shown in FIG. 13 or FIG. 14 .

13. The pharmaceutically acceptable salt of claim 12 , wherein the citrate salt of Compound A has an X-ray powder diffraction pattern corresponding to the representative XRPD spectrum shown in FIG .

The mesylate salt of Compound A is characterized by one or more peaks in an X-ray powder diffraction pattern;
The one or more peaks may include a peak within a range of about 5.0 degrees 2θ to about 5.4 degrees 2θ, a peak within a range of about 8.4 degrees 2θ to about 8.8 degrees 2θ, a peak within a range of about 9.4 degrees 2θ Peaks within the range of degrees 2θ to approximately 9.8 degrees 2θ, peaks within the range of approximately 10.3 degrees 2θ to approximately 10.7 degrees 2θ, and peaks within the range of approximately 12.9 degrees 2θ to approximately 13.3 degrees 2θ can be selected from the peaks within ;
The one or more peaks may include a peak within a range of about 5.0 degrees 2θ to about 5.4 degrees 2θ, a peak within a range of about 9.4 degrees 2θ to about 9.8 degrees 2θ, and a peak within a range of about 10. The one or more peaks may be selected from peaks within a range of about 8.5 degrees 2θ to about 8.9 degrees 2θ; about 12.5 degrees 2θ; may be selected from a peak within a range of 7 degrees 2θ to about 13.1 degrees 2θ, and a peak within a range of about 18.8 degrees 2θ to about 19.2 degrees 2θ;
The one or more peaks may be about 5.2 degrees 2θ ± 0.2 degrees 2θ, about 8.6 degrees 2θ ± 0.2 degrees 2θ, about 9.6 degrees 2θ ± 0.2 degrees 2θ, about 10. may be selected from 5 degrees 2θ ± 0.2 degrees 2θ, and approximately 13.1 degrees 2θ ± 0.2 degrees 2θ; or
The one or more peaks are approximately 8.7 degrees 2θ ± 0.2 degrees 2θ, approximately 12.9 degrees 2θ ± 0.2
13. The pharmaceutically acceptable salt of claim 12 , which may be selected from degrees 2θ, and about 19.0 degrees 2θ ± 0.2 degrees 2θ .

13. The pharmaceutically acceptable salt of claim 12 , wherein the besylate salt of Compound A has an X-ray powder diffraction pattern corresponding to the representative XRPD spectrum shown in FIG .

13. The pharmaceutically acceptable salt of claim 12 , wherein the choline salt of Compound A has an X-ray powder diffraction pattern that corresponds to the representative XRPD spectrum shown in FIG .

Crystalline (E)-3-(4-((1R,3R)-2-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-2,3,4,9-tetrahydro -1H-pyrido[3,4-b]indol-1-yl)-3,5-difluorophenyl)acrylic acid (compound A):

an amount of a pharmaceutically acceptable (E)-3-(4-((1R,3R)-2-(bicyclo[1.1.1]pentan-1-yl)-3-methyl-2,3 ,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-3,5-difluorophenyl)acrylic acid (compound A)

at least two solid forms of Compound A selected from the group consisting of Salt Form A of Compound A, an amount of a pharmaceutically acceptable salt Form C of Compound A , and an amount of an amorphous Compound A; blend.

A pharmaceutical composition comprising an effective amount of a pharmaceutically acceptable salt according to any one of claims 1 to 17, or a mixture according to claim 19, for inhibiting cell growth, comprising :
said cells are identified as cells having estrogen receptor alpha that mediates the growth properties of said cells;
Pharmaceutical composition or mixture .

An effective amount of the pharmaceutically acceptable salt according to any one of claims 1 to 17 for the treatment of estrogen receptor α-dependent and/or estrogen receptor α-mediated diseases or conditions.
or a mixture according to claim 19 .

22. A pharmaceutical composition according to claim 20 or 21, further comprising an amount of amorphous Compound A and/or an amount of Compound A free base.