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