Modulators of the 5-hydroxytryptamine receptor 7 and their method of use

Patent metadata

Field	Value
Publication number	US-12338247-B2
Application number	US-202217709847-A
Country	US
Kind code	B2
Filing date	Mar 31, 2022
Priority date	Nov 15, 2016
Publication date	Jun 24, 2025
Grant date	Jun 24, 2025

Abstract

Pharmaceutical compositions of the invention comprise functionalized lactone derivatives having a disease-modifying action in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.

First claim

What is claimed is:

1. A compound having formula (XXV):

or a pharmaceutically acceptable salt thereof, wherein:
R 2d is

R 1a , R 1b , R 1c , R 1d , and R 1e are at each occurrence independently selected from the group consisting of H, halogen, CN, C 1-6 linear alkyl, and C 1-6 linear alkoxy; and
R 3 is optionally substituted phenyl.

2. The compound of claim 1 , wherein R 2d is unsubstituted phenyl, 4-methoxyphenyl, 4-chlorophenyl, or 4-cyanophenyl.

3. The compound of claim 1 , wherein R 3 is selected from the group consisting of phenyl, 4-Me-phenyl, 2-morpholino-phenyl, 4-Cl-phenyl, 4-cyano-2-morpholino-phenyl, 4-methyl-2-morpholino-phenyl, 4-hydroxy-2-morpholino-phenyl, and 4-OH-phenyl.

4. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

5. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

6. A compound having formula (XXV):

or a pharmaceutically acceptable salt thereof, wherein:
R 2d is

R 1a , R 1b , and R 1e are at each occurrence independently selected from the group consisting of H, halogen, CN, C 1-6 linear alkyl, and C 1-6 linear alkoxy; and
R 3 is optionally substituted phenyl.

7. The compound of claim 6 , wherein R 2d is

8. The compound of claim 6 , wherein R 3 is selected from the group consisting of phenyl, 4-Me-phenyl, 2-morpholino-phenyl, 4-Cl-phenyl, 4-cyano-2-morpholino-phenyl, 4-methyl-2-morpholino-phenyl, 4-hydroxy-2-morpholino-phenyl, and 4-OH-phenyl.

9. A pharmaceutical composition comprising the compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10. A compound having formula (XXV):

or a pharmaceutically acceptable salt thereof, wherein:
R 2d is C 1-6 linear alkyl; and
R 3 is optionally substituted phenyl.

11. The compound of claim 10 , wherein R 2d is methyl.

12. The compound of claim 10 , wherein R 3 is selected from the group consisting of phenyl, 4-Me-phenyl, 2-morpholino-phenyl, 4-Cl-phenyl, 4-cyano-2-morpholino-phenyl, 4-methyl-2-morpholino-phenyl, 4-hydroxy-2-morpholino-phenyl, and 4-OH-phenyl.

13. A pharmaceutical composition comprising the compound of claim 10 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

14. The compound of claim 6 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 10 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Temple
• Praeventix Llc

Inventors

• Canney Daniel J
• Blass Benjamin E
• Blattner Kevin M
• Pippin Douglas A

Classifications

• C07F7/10

  containing nitrogen {having a Si-N linkage} · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D493/10 Primary

  Spiro-condensed systems · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D309/08

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