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

Patent metadata

Field	Value
Publication number	US-12269809-B2
Application number	US-202117517166-A
Country	US
Kind code	B2
Filing date	Nov 2, 2021
Priority date	Sep 10, 2014
Publication date	Apr 8, 2025
Grant date	Apr 8, 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 (II):

or a pharmaceutically acceptable salt thereof, wherein:
R 1a and R 1b are each independently a C 1-6 linear alkyl;
R 3 is selected from a group consisting of 1H-benzo[d]imidazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 1H-indole, optionally substituted pyridin-2-yl, optionally substituted pyridin-3-yl, and optionally substituted pyridin-4-yl; and
n is 1, 2, or 3.

2. A composition comprising an effective amount of at least one compound according to claim 1 .

3. A composition according to claim 2 , further comprising at least one excipient.

4. A method of treating a disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity, said method comprising administering to a subject an effective amount of at least one compound according to claim 1 to treat the disease.

5. The method of claim 4 , wherein the at least one compound is administered in a composition further comprising at least one excipient.

6. The method of claim 4 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular diseases, 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.

7. The method of claim 5 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular diseases, 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.

8. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

9. A composition comprising an effective amount of at least one compound according to claim 8 .

10. A composition according to claim 9 , further comprising at least one excipient.

11. A method of treating a disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity, said method comprising administering to a subject an effective amount of at least one compound according to claim 8 to treat the disease.

12. The method of claim 11 , wherein the at least one compound is administered in a composition further comprising at least one excipient.

13. The method of claim 11 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular diseases, 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.

14. The method of claim 12 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular diseases, 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 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

16. A composition comprising an effective amount of at least one compound according to claim 15 .

17. A composition according to claim 16 , further comprising at least one excipient.

18. A method of treating a disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity, said method comprising administering to a subject an effective amount of at least one compound according to claim 15 to treat the disease.

19. The method of claim 18 , wherein the at least one compound is administered in a composition further comprising at least one excipient.

20. The method of claim 18 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular diseases, 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.

21. The method of claim 19 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular diseases, 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

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D307/28

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D405/12

  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