Prodrugs of riluzole and their method of use

Patent metadata

Field	Value
Publication number	US-10844026-B2
Application number	US-202016748354-A
Country	US
Kind code	B2
Filing date	Jan 21, 2020
Priority date	Mar 16, 2012
Publication date	Nov 24, 2020
Grant date	Nov 24, 2020

Abstract

Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

First claim

What is claimed is:

1. A compound having formula (I):

including hydrates, solvates, pharmaceutically acceptable salts, and complexes thereof, wherein:
R 1 is selected from the group consisting of CR 3a R 3b NH 2 , and CR 3a R 3b NR 7a R 7b ,
R 3a and R 3b are taken together with an atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring comprising two to five carbon atoms and a member selected from the group consisting of O, NR 7a , S, and SO 2 ;
R 7a and R 7b are each independently selected from the group consisting of hydrogen, methyl, COR 12 , and CO 2 R 12 ;
R 12 is C1-C6 alkyl.

2. The compound according to claim 1 , wherein R 1 is CR 3a R 3b NH 2 .

3. The compound according to claim 1 , wherein R 1 is CR 3a R 3b NR 7a R 7b .

4. The compound according to claim 1 , wherein R 3a and R 3b are taken together with an atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring comprising two to five carbon atoms and a member selected from the group consisting of O.

5. The compound according to claim 1 , wherein R 3a and R 3b are taken together with an atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring comprising two to five carbon atoms and a member selected from the group consisting of NR 7a .

6. The compound according to claim 1 , wherein R 3a and R 3b are taken together with an atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring comprising two to five carbon atoms and a member selected from the group consisting of S.

7. The compound according to claim 1 , wherein R 3a and R 3b are taken together with an atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring comprising two to five carbon atoms and a member selected from the group consisting of SO 2 .

Assignees

• Biohaven Pharm Holding Co Ltd
• Univ Rutgers

Inventors

• Smith Garry Robert
• Reitz Allen B
• Mcdonnell Mark
• Chen Suzie
• Vera Matthew D
• Blass Benjamin E
• Pelletier Jeffrey Claude
• Velvadapu Venkata N
• Wrobel Jay Edward

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/428

  condensed with carbocyclic rings · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D277/82 Primary

  Nitrogen atoms · CPC title