Solid forms of selective androgen receptor modulators

Patent metadata

Field	Value
Publication number	US-12053448-B2
Application number	US-202117373771-A
Country	US
Kind code	B2
Filing date	Jul 12, 2021
Priority date	Sep 11, 2007
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present invention relates to solid forms of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide and process for producing the same.

First claim

What is claimed is:

1. A method of treating a condition caused by androgen decline in aging male (ADAM) or androgen decline in female (ADIF) comprising administering a composition comprising a crystalline form A of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide compound, characterized by an X-ray powder diffraction pattern displaying peaks at °2θ (d value Å) angles of about 5.6 (15.9), 7.5 (11.8), 8.6 (10.3), 9.9 (8.9), 12.4 (7.1), 15.0 (5.9), 16.7 (5.3), 17.3 (5.1), 18.0 (4.9), 18.5 (4.8), 19.3 (4.6), 19.8 (4.5), 20.6 (4.3), 21.8 (4.1), 22.3 (4.0), 23.4 (3.8), 23.9 (3.7), 24.6 (3.6), 24.9 (3.6), 25.4 (3.5), 26.0 (3.4), 26.5 (3.4) and 27.8 (3.2).

2. The method of claim 1 , wherein said condition caused by androgen decline in aging male (ADAM) is selected from fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, benign prostate hyperplasia, and prostate cancer or any combination thereof.

3. The method of claim 1 , wherein said condition caused by androgen decline in female (ADIF) is selected from sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, depression, anemia, hair loss, obesity, endometriosis, uterine cancer, and ovarian cancer or any combination thereof.

4. A method of treating chronic muscular wasting comprising administering a composition comprising a crystalline form A of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide compound, characterized by an X-ray powder diffraction pattern displaying peaks at °2θ (d value Å) angles of about 5.6 (15.9), 7.5 (11.8), 8.6 (10.3), 9.9 (8.9), 12.4 (7.1), 15.0 (5.9), 16.7 (5.3), 17.3 (5.1), 18.0 (4.9), 18.5 (4.8), 19.3 (4.6), 19.8 (4.5), 20.6 (4.3), 21.8 (4.1), 22.3 (4.0), 23.4 (3.8), 23.9 (3.7), 24.6 (3.6), 24.9 (3.6), 25.4 (3.5), 26.0 (3.4), 26.5 (3.4) and 27.8 (3.2).

5. A method of treating prostate cancer comprising administering a composition comprising a crystalline form A of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide compound, characterized by an X-ray powder diffraction pattern displaying peaks at °2θ (d value Å) angles of about 5.6 (15.9), 7.5 (11.8), 8.6 (10.3), 9.9 (8.9), 12.4 (7.1), 15.0 (5.9), 16.7 (5.3), 17.3 (5.1), 18.0 (4.9), 18.5 (4.8), 19.3 (4.6), 19.8 (4.5), 20.6 (4.3), 21.8 (4.1), 22.3 (4.0), 23.4 (3.8), 23.9 (3.7), 24.6 (3.6), 24.9 (3.6), 25.4 (3.5), 26.0 (3.4), 26.5 (3.4) and 27.8 (3.2).

6. A process for the preparation of a crystalline form D of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide, wherein said crystalline form D of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide has:
a. an X-ray powder diffraction pattern comprising unique peaks at °2θ (d value Å); angles of 4.4 (19.9), 8.5 (10.4), 8.8 (10.0), 11.3 (7.8), 12.7 (6.9), 13.8 (6.4), 14.4 (6.1), 14.6 (6.0), 15.1 (5.8), 16.1 (5.5), 16.6 (5.3), 16.9 (5.2), 18.0 (4.9), 18.7 (4.7), 19.0 (4.6), 19.4 (4.55), 20.8 (4.25), 22.1 (4.0), 22.7 (3.9), 23.1 (3.8), 23.4 (3.8), 24.7 (3.6), 24.9 (3.56), 25.3 (3.51), 27.8 (3.2), 29.3 (3.0); and
b. a melting point of 130° C.,

the process comprising heating a sample of other forms of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide to 110° C. in the presence of form D.

7. A process for the preparation of a crystalline form D of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide, wherein said crystalline form D of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide has:
a. an X-ray powder diffraction pattern comprising unique peaks at °2θ (d value Å); angles of 4.4 (19.9), 8.5 (10.4), 8.8 (10.0), 11.3 (7.8), 12.7 (6.9), 13.8 (6.4), 14.4 (6.1), 14.6 (6.0), 15.1 (5.8), 16.1 (5.5), 16.6 (5.3), 16.9 (5.2), 18.0 (4.9), 18.7 (4.7), 19.0 (4.6), 19.4 (4.55), 20.8 (4.25), 22.1 (4.0), 22.7 (3.9), 23.1 (3.8), 23.4 (3.8), 24.7 (3.6), 24.9 (3.56), 25.3 (3.51), 27.8 (3.2), 29.3 (3.0); and
b. a melting point of 130° C.,

the process comprising “seeding” a sample of other forms of (S)—N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide with a small amount of crystalline form D and storing the sample at 110° C./0% RH for 7 days or at 50° C. in water for 24 hours.

Assignees

• Univ Tennessee Res Found

Inventors

• Dalton James T
• Bird Thomas G
• Ahn Tai
• Dickason David A
• Hong Seoung-Soo

Classifications

• B60R16/033

  characterised by the use of electrical cells or batteries (for propulsion puposes B60K1/04; supplying batteries to, or removing batteries from, vehicles B60S5/06; testing of charge state G01R31/36) · CPC title

• B60R5/04

  arranged at rear of vehicle {(B60R5/003, B60R5/006 take precedence; external trunks arranged at rear of vehicle B60R9/065)} · CPC title

• B62J9/27

  characterised by mounting arrangements, e.g. quick release arrangements · CPC title

• C07C253/30

  by reactions not involving the formation of cyano groups · CPC title

• C07C255/60

  at least one of the singly-bound nitrogen atoms being acylated · CPC title