LSD1 inhibitors and medical uses thereof

Patent metadata

Field	Value
Publication number	US-11013718-B2
Application number	US-201916671559-A
Country	US
Kind code	B2
Filing date	Nov 1, 2019
Priority date	Oct 26, 2016
Publication date	May 25, 2021
Grant date	May 25, 2021

Abstract

Provided are novel compounds of Formula (I or Ia′): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with LSD1. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I or Ia′), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with LSD1.

First claim

The invention claimed is:

1. A compound of the Formula:

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein the compound is of the Formula:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , wherein the enantiomeric purity of the compound is at least 97%.

4. The compound of claim 2 , wherein the enantiomeric purity of the compound is at least 98%.

5. The compound of claim 2 , wherein the enantiomeric purity of the compound is at least 99%.

6. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition comprising an effective amount of a compound of claim 2 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

8. A method of treating a disease that is treatable by inhibiting LSD1 wherein said disease is selected from HIV, prostate cancer, esophageal squamous cell, neuroblastoma, ovarian cancer, bladder cancer, lung cancer, colorectal cancer, squamous cell carcinomas, breast cancer, glioblastoma multiforme, chondrosarcoma, Ewing's sarcoma, osteogenic sarcoma, rhabdomyosarcoma, melanoma, or medulloblastoma comprising the step of administering to a subject in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

9. A method of treating a disease that is treatable by inhibiting LSD1 wherein said disease is selected from HIV, prostate cancer, esophageal squamous cell, neuroblastoma, ovarian cancer, bladder cancer, lung cancer, colorectal cancer, squamous cell carcinomas, breast cancer, glioblastoma multiforme, chondrosarcoma, Ewing's sarcoma, osteogenic sarcoma, rhabdomyosarcoma, melanoma, or medulloblastoma comprising the step of administering to a subject in need thereof a compound of claim 2 , or a pharmaceutically acceptable salt thereof.

10. A compound having the Formula:

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 10 , wherein the compound is of the Formula:

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 11 , wherein the enantiomeric purity of the compound is at least 97%.

13. The compound of claim 11 , wherein the enantiomeric purity of the compound is at least 98%.

14. The compound of claim 11 , wherein the enantiomeric purity of the compound is at least 99%.

15. A pharmaceutical composition comprising an effective amount of a compound of claim 10 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition comprising an effective amount of a compound of claim 11 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

17. A method of treating a disease that is treatable by inhibiting LSD1 wherein said disease is selected from HIV, prostate cancer, esophageal squamous cell, neuroblastoma, ovarian cancer, bladder cancer, lung cancer, colorectal cancer, squamous cell carcinomas, breast cancer, glioblastoma multiforme, chondrosarcoma, Ewing's sarcoma, osteogenic sarcoma, rhabdomyosarcoma, melanoma, or medulloblastoma comprising the step of administering to a subject in need thereof a compound of claim 10 , or a pharmaceutically acceptable salt thereof.

18. A method of treating a disease that is treatable by inhibiting LSD1 wherein said disease is selected from HIV, prostate cancer, esophageal squamous cell, neuroblastoma, ovarian cancer, bladder cancer, lung cancer, colorectal cancer, squamous cell carcinomas, breast cancer, glioblastoma multiforme, chondrosarcoma, Ewing's sarcoma, osteogenic sarcoma, rhabdomyosarcoma, melanoma, or medulloblastoma comprising the step of administering to a subject in need thereof a compound of claim 11 , or a pharmaceutically acceptable salt thereof.

Assignees

• Constellation Pharmaceuticals Inc

Inventors

• Brucelle Francois
• Gehling Victor S
• Khanna Avinash

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D221/20

  Spiro-condensed ring systems · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P31/18

  for HIV · CPC title

• A61K31/438

  The ring being spiro-condensed with carbocyclic or heterocyclic ring systems · CPC title