Bivalent AMPA receptor positive allosteric modulators

Patent metadata

Field	Value
Publication number	US-9328125-B2
Application number	US-201414474258-A
Country	US
Kind code	B2
Filing date	Sep 1, 2014
Priority date	Mar 1, 2012
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

Embodiments of the invention are directed to compounds that are positive allosteric modulators of AMPA receptors.

First claim

The invention claimed is:

1. A positive allosteric modulator of AMPA receptors (AMPAR) having a general formula of Formula I:

where R 1 and R 2 are independently hydrogen, C 1 -C 6 alkyl or C 1 -C 6 heteroalkyl; and
R 3 is hydrogen, nitro, amine, cyano, substituted or unsubstituted sulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; and
n is 0; and
L is —C(O)—;
X is a indole, indazole, or pyridine.

2. The positive allosteric modulator of claim 1 , wherein R 1 and R 2 are independently C 1 -C 6 alkyl.

3. The positive allosteric modulator of claim 1 , wherein R 1 is methyl or isopropyl.

4. The positive allosteric modulator of claim 1 , wherein R 2 is methyl.

5. The positive allosteric modulator of claim 1 , wherein X is pyridine.

6. The positive allosteric modulator of claim 1 , wherein R 3 is substituted or unsubstituted N-containing C 5 -C 6 heterocyclyl.

7. The positive allosteric modulator of claim 1 , wherein the modulator is selected from Propane-2-sulfonic acid (2-{4-[2-(pyrrolidine-1-carbonyl)-pyridin-4-yl]-phenyl}-propyl)-amide (HJC-1-22); Propane-2-sulfonic acid (2-{4-[5-(piperidine-1-carbonyl)-indol-1-yl]-phenyl}-propyl)amide (HJC-1-24); Propane-2-sulfonic acid (2-{4-[5-(piperidine-1-carbonyl)-pyridin-2-yl]-phenyl}-propyl)-amide (HJC-1-59); Propane-2-sulfonic acid (2-{4-[5-(piperidine-1-carbonyl)-indazol-1-yl]-phenyl}-propyl)-amide (HJC-2-8); Propane-2-sulfonic acid (2-{4-[5-(pyrrolidine-1-carbonyl)-indol-1-yl]-phenyl}-propyl)amide (HJC-2-10); Propane-2-sulfonic acid (2-{4-[5-(4-methyl-piperazine-1-carbonyl)-indol-1-yl]-phenyl}-propyl)amide (HJC-2-22); Propane-2-sulfonic acid (2-{4-[5-(piperazine-1-carbonyl)-indol-1-yl]-phenyl}-propyl)amide (HJC-2-37); Propane-2-sulfonic acid (2-{4-[5-(4-methanesulfonyl-piperazine-1-carbonyl)-indol-1-yl]-phenyl}-propyl)amide (HJC-2-67); Propane-2-sulfonic acid (2-{4-[5-(4-acetyl-piperazine-1-carbonyl)-indol-1-yl]-phenyl}-propyl)amide (HJC-2-68); Propane-2-sulfonic acid (2-{4-[2-(piperidine-1-carbonyl)-pyridin-4-yl]-phenyl}-propyl)-amide (HJC-2-69); or Propane-2-sulfonic acid (2-{4-[5-(pyrrolidine-1-carbonyl)-pyridin-2-yl]-phenyl}-propyl)-amide (HJC-2-70).

8. The positive allosteric modulator of claim 1 , wherein the modulator is Propane-2-sulfonic acid (2-{4-[2-(pyrrolidine-1-carbonyl)-pyridin-4-yl]-phenyl}-propyl)-amide (HJC-1-22).

Assignees

• Zhou Jia
• Chen Haijun
• Johnson Kenneth M
• Wang Cheng Z
• Univ Texas

Inventors

• Zhou Jia
• Chen Haijun
• Johnson Kenneth M
• Wang Cheng Z

Classifications

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D209/08

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07D231/56

  Benzopyrazoles; Hydrogenated benzopyrazoles · CPC title

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title

• C07D401/12

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