SUBSTITUTED- 1H-BENZO[D]IMIDAZOLE SERIES COMPOUNDS AS LYSINE-SPECIFIC DEMETHYLASE 1 (LSD1) INHIBITORS

• US 20150065495A1
• Filed: 08/28/2014
• Published: 03/05/2015
• Est. Priority Date: 08/30/2013
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah (State of Utah)
• Inventors: Vankayalapati, Hariprasad, Sharma, Sunil, Sorna, Venkataswamy
• Granted Patent: US 9,556,170 B2
• Time in Patent Office: Days
• US Class Current: 514/228.2
• CPC Class Codes: C07D 235/32 Benzimidazole-2-carbamic acids, unsubstituted or substituted; Esters thereof; Thio-analogues thereof
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The present invention provides compounds which are useful as inhibitors of lysine-specific demethylase 1 (“LSD1”). The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to a method for preparing these compounds. The present invention also relates to a method of treating a mammalian disorder in which LSD1 levels are elevated by administering these compounds and compositions to a patient in need thereof. The present invention also relates to a method for decreasing histone demethylase activity in a mammal comprising administering to the mammal an effective amount of these compounds and compositions.

Claims

1. A compound of Formula I

2. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 as an active agent in said composition and a pharmaceutically acceptable carrier.

3. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound of claim 1.

4. A method for treatment of a mammalian disorder in which lysine-specific demethylase 1 (LSD1) levels are elevated comprising administering to a patient in need thereof an effective amount of a compound of claim 1.

5. A method for decreasing histone demethylase activity in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound of claim 1.

6. A compound selected from the group consisting of:

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 as an active agent in said composition and a pharmaceutically acceptable carrier.

8. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound of claim 6.

9. A method for treatment of a mammalian disorder in which lysine-specific demethylase 1 (LSD1) levels are elevated comprising administering to a patient in need thereof an effective amount of a compound of claim 6.

10. A method for decreasing histone demethylase activity in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound of claim 6.

11. A compound having a structure represented by a formula:

12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 11 as an active agent in said composition and a pharmaceutically acceptable carrier.

13. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound of claim 11.

14. A method for treatment of a mammalian disorder in which lysine-specific demethylase 1 (LSD1) levels are elevated comprising administering to a patient in need thereof an effective amount of a compound of claim 11.

15. A method for decreasing histone demethylase activity in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound of claim 11.