Cyclopropylamines as LSD1 inhibitors

• US 9,670,210 B2
• Filed: 02/12/2015
• Issued: 06/06/2017
• Est. Priority Date: 02/13/2014
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: He, Chunhong, Wu, Liangxing, Yao, Wenqing, Zhang, Fenglei
• Primary Examiner(s): O DELL, DAVID K
• Application Number:
  US14/620,903
• Publication Number:
  US 20150225401A1
• Time in Patent Office: 845 Days
• Field of Search: None
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/4523 containing further heterocyclic ring systems
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 211/14 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 211/16 with acylated ring nitrogen atom
• CPC Class Codes: C07D 211/32 by oxygen 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 401/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/10 : Spiro-condensed systems

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 1-{[4-(methoxymethyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acid, or a pharmaceutically acceptable salt thereof.

8. A compound of claim 1, which is 1-{[4-(ethoxymethyl)-4-({[(1R, 2S)-2-phenylcyclopropyl]amino }methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid.

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

16. A pharmaceutical composition comprising the compound of claim 8 and at least one pharmaceutically acceptable carrier or excipient.

2. A compound which is 1-{[4-(methoxymethyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopentanecarboxylic acid.

10. A pharmaceutical composition comprising the compound of claim 2 and at least one pharmaceutically acceptable carrier or excipient.

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

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

4. A compound which is 1-{[4-(methoxymethyl)-4-({[(1R, 2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid.

12. A pharmaceutical composition comprising the compound of claim 4 and at least one pharmaceutically acceptable carrier or excipient.

5. A compound which is 1-{[4-({[(1R, 2S)-2-(4-fluorophenyl)cyclopropyl]amino}methyl)-4-(methoxymethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, or a pharmaceutically acceptable salt thereof.

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

6. A compound which is 1-{[4-({[(1R, 2S)-2-(4-fluorophenyl)cyclopropyl]amino}methyl)-4-(methoxymethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid.

14. A pharmaceutical composition comprising the compound of claim 6 and at least one pharmaceutically acceptable carrier or excipient.

7. A compound which is 1-{[4-(ethoxymethyl)-4-({[(1R, 2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, or a pharmaceutically acceptable salt thereof.

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