Neuropeptide S receptor (NPSR) agonists

Patent metadata

Field	Value
Publication number	US-11220526-B2
Application number	US-201716090728-A
Country	US
Kind code	B2
Filing date	Mar 23, 2017
Priority date	Apr 4, 2016
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

Neuropeptide S receptor agonists are provided. The NPS agonists include trimeric, tetrameric, pentameric or hexameric peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The peptidomimetic molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling.

First claim

What is claimed is:

1. A compound according to Formula (IC):

wherein
R 3′ is H, lysine side chain, C 1 -C 3 alkylated or benzylated lysine side chain, alanine side chain, unbranched C 1 -C 6 alkyl, (CH 2 ) 4 NHCOCF 3 , or benzyl optionally substituted with nitro;
B is a five membered saturated ring substituted with one C(O)NH 2 group, or a six membered saturated or aromatic ring substituted with one C(O)NH 2 group; and
E is

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein R 3′ is a lysine side chain, —(CH 2 ) 4 —NH 2 .

3. The compound according to claim 1 , wherein B is a six membered saturated or aromatic ring substituted with one C(O)NH 2 group.

4. A method for treating a subject having a condition or disorder where modulation of neuropeptide S receptor activity is of therapeutic benefit, wherein such disorder or condition is selected from the group consisting of substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, and schizophrenia, comprising administering to said subject having said condition or disorder a therapeutically effective amount of a compound according to claim 1 .

5. The method of claim 4 , further comprising administering an effective amount of a second therapeutically effective agent.

Assignees

• Res Triangle Inst
• Univ California

Inventors

• Runyon Scott
• Harris Danni
• Reinscheid Rainer
• Zhang Yanyan
• Hassler Carla

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K5/0827

  containing heteroatoms different from O, S, or N · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title

• C07K5/101

  the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu · CPC title

• C07K5/0812

  and aromatic or cycloaliphatic · CPC title