5-hydroxytryptamine receptor 7 activity modulators and their method of use

Patent metadata

Field	Value
Publication number	US-10676464-B2
Application number	US-201916411534-A
Country	US
Kind code	B2
Filing date	May 14, 2019
Priority date	Mar 11, 2013
Publication date	Jun 9, 2020
Grant date	Jun 9, 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 according to the following formula,

or a pharmaceutically acceptable salt thereof, wherein
n is 2;
each of R 1a and R 1b is C 1-6 linear alkyl; and
R 3 is optionally substituted aryl.

2. The compound of claim 1 , wherein each of R 1a and R 1b is ethyl.

3. The compound of claim 1 , wherein R 3 is optionally substituted phenyl.

4. The compound of claim 3 , wherein R 3 is unsubstituted phenyl.

5. The compound of claim 3 , wherein R 3 is substituted phenyl.

6. The compound of claim 3 , wherein R 3 is selected from the group consisting of 4-hydroxyphenyl, 4-nitrophenyl, 4-cyanophenyl, 2-hydroxyphenyl, 3-methoxyphenyl, 3-hydroxyphenyl, unsubstituted phenyl, 2-isopropylphenyl.

7. The compound of claim 1 , having the following structure,

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , having the following structure,

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising:
a compound according to claim 1 , or a pharmaceutically acceptable salt thereof; and
one or more pharmaceutically acceptable carriers.

10. A method of treating a disease that involves dysregulation of the 5-hydroxytryptamine receptor 7 (5-HT 7 ) in patient in need thereof, wherein said method comprises administering to a patient in need thereof an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and
wherein the disease is circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulation disorder, learning disorder, memory disorder, hippocampal signaling disorder, sleep disorder, attention deficit/hyperactivity disorder, anxiety, avoidant personality disorder, premature ejaculation, eating disorder, premenstrual syndrome, premenstrual dysphonic disorder, seasonal affective disorder, or bipolar disorder.

11. A compound according to the following formula,

or a pharmaceutically acceptable salt thereof, wherein
n is 2;
R 1a and R 1b , taken together with the atom to which they are bound, form a cyclopentyl group; and
R 3 is optionally substituted aryl.

12. The compound of claim 11 , wherein R 3 is optionally substituted phenyl.

13. A pharmaceutical composition comprising:
a compound according to claim 11 , or a pharmaceutically acceptable salt thereof; and
one or more pharmaceutically acceptable carriers.

14. A method of treating a disease that involves dysregulation of the 5-hydroxytryptamine receptor 7 (5-HT 7 ) in patient in need thereof, wherein said method comprises administering to a patient in need thereof an effective amount of a compound according to claim 11 , or a pharmaceutically acceptable salt thereof, and
wherein the disease is circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulation disorder, learning disorder, memory disorder, hippocampal signaling disorder, sleep disorder, attention deficit/hyperactivity disorder, anxiety, avoidant personality disorder, premature ejaculation, eating disorder, premenstrual syndrome, premenstrual dysphonic disorder, seasonal affective disorder, or bipolar disorder.

15. A compound according to the following formula,

or a pharmaceutically acceptable salt thereof, wherein
n is 2;
R 1a and R 1b , taken together with the atom to which they are bound, form a cyclohexyl group; and
R 3 is optionally substituted aryl.

16. The compound of claim 15 , wherein R 3 is optionally substituted phenyl.

17. A pharmaceutical composition comprising:
a compound according to claim 15 , or a pharmaceutically acceptable salt thereof; and
one or more pharmaceutically acceptable carriers.

18. A method of treating a disease that involves dysregulation of the 5-hydroxytryptamine receptor 7 (5-HT 7 ) in patient in need thereof, wherein said method comprises administering to a patient in need thereof an effective amount of a compound according to claim 15 , or a pharmaceutically acceptable salt thereof, and
wherein the disease is circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulation disorder, learning disorder, memory disorder, hippocampal signaling disorder, sleep disorder, attention deficit/hyperactivity disorder, anxiety, avoidant personality disorder, premature ejaculation, eating disorder, premenstrual syndrome, premenstrual dysphonic disorder, seasonal affective disorder, or bipolar disorder.

Assignees

• Univ Temple

Inventors

• Canney Daniel J
• Blass Benjamin E
• Gao Rong
• Abou-Gharbia Magid

Classifications

• C07D307/33

  in position 2, the oxygen atom being in its keto or unsubstituted enol form · CPC title

• C07D405/12 Primary

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

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D307/94

  spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title