Cyclopropylamines as LSD1 inhibitors

• US 9,994,546 B2
• Filed: 10/07/2016
• Issued: 06/12/2018
• Est. Priority Date: 02/13/2014
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: Wu, Liangxing, Yao, Wenqing
• Primary Examiner(s): O DELL, DAVID K
• Application Number:
  US15/288,605
• Publication Number:
  US 20170121302A1
• Time in Patent Office: 613 Days
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 205/04 having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/34 with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 211/98 Nitrogen atom
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Claims

1. A compound which is 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide, or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

2. A compound which is 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide.

4. A pharmaceutical composition comprising a compound of claim 2, and at least one pharmaceutically acceptable carrier.

5. A compound which is 3-(cyanomethyl)-N,N-dimethyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide, or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising a compound of claim 5, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

6. A compound which is 3-(cyanomethyl)-N,N-dimethyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide.

8. A pharmaceutical composition comprising a compound of claim 6, and at least one pharmaceutically acceptable carrier.

9. A compound which is 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound of claim 9, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

10. A compound which is 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide.

12. A pharmaceutical composition comprising a compound of claim 10, and at least one pharmaceutically acceptable carrier.