Selective estrogen receptor degraders

Patent metadata

Field	Value
Publication number	US-11117902-B2
Application number	US-202016876819-A
Country	US
Kind code	B2
Filing date	May 18, 2020
Priority date	Jul 12, 2018
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Novel selective estrogen receptor degraders (SERDs) according to the formula:pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein either R1 or R2 is independently selected from Cl, F, —CF3, or —CH3, and the other is hydrogen, and methods for their use are provided.

First claim

We claim:

1. A crystalline form of the compound of the formula:

wherein either R 1 or R 2 is independently selected from Cl, F, —CF 3 , or —CH 3 , and the other is hydrogen,
or a pharmaceutically acceptable salt thereof.

2. A crystalline form according to claim 1 , wherein the compound is

pharmaceutically acceptable salt thereof.

3. A crystalline form according to claim 2 , characterized by having an X-ray powder diffraction (XRPD) pattern comprising peaks at ° 2θ values of 19.8±0.2, in combination with one or more of the peaks selected from the group consisting of 6.8±0.2, 16.0±0.2, and 22.1±0.2.

4. A crystalline form according to claim 2 , characterized by having an X-ray powder diffraction (XRPD) pattern comprising peaks at ° 2θ values of

Angle
Relative Intensity (% of

Peak
(°2-Theta) +/− 0.2°
most intense peak)

1
6.8
29.40

2
15.3
8.30

3
16.0
20.10

4
17.4
7.60

5
18.1
16.00

6
19.8
100.00

7
21.1
14.60

8
22.1
28.90

9
24.9
16.40

10
25.4
21.90.

5. A crystalline form according to claim 2 , wherein the pharmaceutically acceptable salt is a benzenesulfonic acid salt.

6. A crystalline form according to claim 5 , characterized by having an X-ray powder diffraction (XRPD) pattern comprising peaks at ° 2θ values of wherein the compound is 20.5±0.2 in combination with one or more of the peaks selected from the group consisting of 12.3±0.2, 22.2±0.2, and 23.1±0.2.

7. A crystalline form according to claim 5 , characterized by having an X-ray powder diffraction (XRPD) pattern comprising peaks at ° 2θ values of

Angle
Relative Intensity

(°2-Theta) +/−
(% of most intense

Peak
0.2°
peak)

1
7.6
27.10

2
10.6
34.50

3
12.3
42.10

4
12.6
32.30

5
17.7
32.80

6
19.2
26.70

7
20.5
100.00

8
22.2
45.50

9
23.1
36.30

10
24.2
29.80.

8. A crystalline form according to claim 2 , wherein the pharmaceutically acceptable salt is a 4-methylbenzenesulfonic acid salt.

9. A crystalline form according to claim 8 , characterized by having an X-ray powder diffraction (XRPD) pattern comprising peaks at ° 2θ values of wherein the compound is 20.1±0.2 in combination with one or more of the peaks selected from the group consisting of 12.8±0.2, 19.5±0.2, and 22.8±0.2.

10. A crystalline form according to claim 8 , characterized by having an X-ray powder diffraction (XRPD) pattern comprising peaks at ° 2θ values of

Angle
Relative Intensity (%

Peak
(°2-Theta) +/− 0.2°
of most intense peak)

1
7.6
25.70

2
12.4
27.90

3
12.8
36.80

4
18.9
26.50

5
19.5
56.90

6
20.1
100.00

7
20.9
41.50

8
21.8
40.90

9
22.8
39.40

10
25.4
29.70.

Assignees

• Lilly Co Eli

Inventors

• Bastian Jolie Anne
• Cohen Jeffrey Daniel
• Rubio Almudena
• Sall Daniel Jon
• McMahon Jennifer Anne

Classifications

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• C07D491/052 Primary

  the oxygen-containing ring being six-membered · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title