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

Patent metadata

Field	Value
Publication number	US-11319327-B2
Application number	US-202017015696-A
Country	US
Kind code	B2
Filing date	Sep 9, 2020
Priority date	Nov 15, 2016
Publication date	May 3, 2022
Grant date	May 3, 2022

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 selected from the group consisting of C 1-6 linear alkyl, —(CH 2 ) q CN, —(CH 2 ) q SO 2 R 13 ,

R 1a , R 1b , R 1c , R 1d , and R 1c 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;
R 3 is selected from a group consisting of optionally substituted phenyl or

R 13 is C 1-6 linear alkyl; and
q is 1, 2, or 3.

2. The compound of claim 1 , wherein R 2 d is

3. The compound of claim 1 , wherein R 2d is C 1-6 linear alkyl.

4. The compound of claim 1 , wherein R 2d is selected from the group consisting of methyl, unsubstituted phenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-cyanophenyl, —(CH 2 )CN, —(CH 2 )SO 2 Me,

5. 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, 4-OH-phenyl, and 2-methyl-1H-benzo[d]imidazol-4-yl.

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

or a pharmaceutically acceptable salt thereof.

7. A composition comprising an effective amount of at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

8. The composition according to claim 7 , further comprising at least one excipient.

9. 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 the claim 1 to treat the disease.

10. The method of claim 9 , wherein the at least one compound is administered in a composition further comprising at least one excipient.

11. The method of claim 9 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: inflammatory bowel disease, 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.

12. The method of claim 10 , wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity comprises: inflammatory bowel disease, 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

• 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

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P29/02

  without antiinflammatory effect · CPC title

• C07D491/107 Primary

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

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title