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

Patent metadata

Field	Value
Publication number	US-10858368-B2
Application number	US-201716349811-A
Country	US
Kind code	B2
Filing date	Nov 15, 2017
Priority date	Nov 15, 2016
Publication date	Dec 8, 2020
Grant date	Dec 8, 2020

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 (I):

Including hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein:
A is selected from a group consisting of

X is selected from the group consisting of O, S, SO, SO 2 , NR;
n 1 is 0, 1, 2;
n 2 is 0, 1, 2;
R is selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, C 3-7 cycloalkyl,

COR 2 , CO 2 R 2a , CONR 2b R 2c , SO 2 NR 2b R 2c , and SO 2 R 2d ; R 1a , R 1b , R 1c , R 1d and R 1e are at each occurrence independently selected from the group consisting of H, OH, NO 2 , halogen, CN, C 1-6 linear alkyl, C 3-7 branched alkyl, C 3-7 cycloalkyl, C 1-6 linear alkoxy, C 3-7 branched alkoxy, C 3-7 cycloalkoxy, C 1-6 linear haloalkyl, C 3-7 branched haloalkyl, C 1-6 linear haloalkoxy, —S(C 1-6 linear alkyl), S(C 3-7 branched alkyl), —S(C 3-7 cycloalkyl), COR 6 , CO 2 R 7 , CONR 8a R 8b , SO 2 NR 8a R 8b , NR 9a R 9b , NR 9a COR 10 , NR 9a SO 2 R 11 , and NR 9a SO 2 NR 12a R 12b ;
R 2 is selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 2a is selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 2b is selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 2c is selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 2d is selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, C 3-7 cycloalkyl, C 1-6 linear haloalkyl, C 3-7 branched haloalkyl, —(CH 2 ) q CN, —(CH 2 ) q SO 2 R 13 , —(CH 2 ) q OR 14 ,

R 3 is selected from a group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, C 3-7 cycloalkyl, optionally substituted aryl,

R 4 is an optionally substituted aryl;
R 5a and R 5b are each independently optionally substituted aryl;
R 6 is at each occurrence independently selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 7 is at each occurrence independently selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 8a is at each occurrence independently selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 8b is at each occurrence independently selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 9a is at each occurrence independently selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 9b is at each occurrence independently selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 10 is at each occurrence independently selected from the group consisting of H, C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 11 is at each occurrence independently selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 12a is at each occurrence independently selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 12b is at each occurrence independently selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 13 is selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
R 14 is selected from the group consisting of C 1-6 linear alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl;
n is 1, 2, or 3;
m is 1 or 2;
and q is 1, 2, or 3.

2. The compound of claim 1 , having the formula (II):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

3. The compound of claim 1 , having the formula (III):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

4. The compound of claim 1 , having the formula (IV):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

5. The compound of claim 1 , having the formula (V):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

6. The compound of claim 1 , having the formula (VI):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

7. The compound of claim 1 , having the formula (VII):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

8. The compound of claim 1 , having the formula (VIII):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

9. The compound of claim 1 , having the formula (IX):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

10. The compound of claim 1 , having the formula (X):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

11. The compound of claim 1 , having the formula (XI):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

12. The compound of claim 1 , having the formula (XII):

Including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs and complexes thereof.

13. The

Assignees

• Temple University—Of the Commonwealth System of Higher Education
• 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

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D493/10 Primary

  Spiro-condensed systems · CPC title

• C07D491/107 Primary

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title