18-20 member bi-polycyclic compounds

Patent metadata

Field	Value
Publication number	US-10752591-B2
Application number	US-201916502092-A
Country	US
Kind code	B2
Filing date	Jul 3, 2019
Priority date	Jun 4, 2014
Publication date	Aug 25, 2020
Grant date	Aug 25, 2020

Abstract

The invention relates to a method of inhibiting loss of muscle mass or muscle function in a subject in need thereof, or a method of treating miofibers ex vivo, the method comprising administering a therapeutically effective amount of a 18-20 member bi-polycyclic compound to the subject or to the miofibers.

First claim

The invention claimed is:

1. A method of inhibiting loss of muscle mass or muscle function in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I:
A-W—Z  (I)

or a pharmaceutically acceptable salt thereof, or a composition comprising thereof, wherein A is

W is a heterocyclylene, arylene, heteroarylene, alkenylenearylene, arylenealkenylene alkenyleneheteroarylene, or heteroarylenealkenylene; and
Z is a hydrogen bond donor.

2. The method of claim 1 , wherein W is an indolinylene linked to A at any one of positions 2, 3, 4, 5, 6 or 7 of the indolinylene; a quinolinene linked to A at any one of positions 2, 3, 4, 5, 6, 7, or 8; or an isoquinolinene linked to A at any one of positions 1, 3, 4, 5, 6, 7, or 8.

3. The method of claim 1 , wherein W is -propylene-phenylene-.

4. The method of claim 1 , wherein Z is —C(O)NR 1 R 2 or —C(O)OR 3 , wherein R 1 and R 2 are each independently hydrogen (H), hydroxyl (OH), C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, or aminoaryl; and R 3 is H or C 1-6 alkyl.

5. The method of claim 2 , wherein Z is linked to the indolinylene, quinolinene, or isoquinolinene at any one of the positions that is not linked to A.

6. The method of claim 1 , wherein W is an indolinylene linked to A at any one of positions 2, 3, 4, 5, 6 or 7 of the indolinylene; Z is —C(O)NR 1 R 2 or —C(O)OR 3 , wherein R 1 and R 2 are each independently hydrogen, hydroxyl, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, or aminoaryl; and R 3 is H or C 1-6 alkyl, and wherein Z is linked to the indolinylene at any one of positions 2, 3, 4, 5, 6 or 7 of the indolinylene not linked to A.

7. The method of claim 1 , wherein W is a quinolinene linked to A at any one of positions 2, 3, 4, 5, 6, 7 or 8 of the quinolinene; Z is —C(O)NR 1 R 2 or —C(O)OR 3 , wherein R 1 and R 2 are each independently hydrogen, hydroxyl, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, or aminoaryl; and R 3 is H or C 1-6 alkyl, and wherein Z is linked to the quinolinene at any one of positions 2, 3, 4, 5, 6, 7 or 8 of the quinolinene.

8. The method of claim 1 , wherein W is a isoquinolinene linked to A at one of positions 1, 3, 4, 5, 6, 7 or 8 of the isoquinolinene moiety; Z is —C(O)NR 1 R 2 or —C(O)OR 3 , wherein R 1 and R 2 are each independently hydrogen, hydroxyl, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, or aminoaryl; and R 3 is H or C 1-6 alkyl, and wherein Z is linked to the quinoline ring at any one of positions 2, 3, 4, 5, 6, 7 or 8 of the isoquinolinene.

9. The method of claim 1 , wherein the compound is

10. The method of claim 1 , wherein the loss of muscle mass is associated with any one of an inherited myopathy, muscular dystrophy, neuromyotonia, nemaline myopathy, multi/minicore myopathy, centronuclear myopathy, mitochondrial myopathy, inflammatory myopathy, metabolic myopathy, intensive care unit-acquired weakness (ICUAW), chronic obstructive pulmonary disease (COPD), heart failure, traumatic injury or malignancy.

11. The method of claim 1 , wherein W is a napthyl radical.

Assignees

• Haro Pharmaceutical Inc
• The Royal Institution For The Advancement Of Learning/Mcgill Univ
• Univ Montreal
• Haro Pharmaceuticals Inc

Inventors

• Bettoun David
• Martinez Eduardo
• Gleason James
• Mader Sylvie
• Xing Shuo

Classifications

• C07D215/54 Primary

  attached in position 3 · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07D209/42

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D409/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07C2602/10

  the other ring being six-membered, e.g. tetraline · CPC title