EPAC antagonists

Patent metadata

Field	Value
Publication number	US-11124489-B2
Application number	US-201816499050-A
Country	US
Kind code	B2
Filing date	Mar 29, 2018
Priority date	Mar 31, 2017
Publication date	Sep 21, 2021
Grant date	Sep 21, 2021

Abstract

Embodiments are directed to a series of novel EPAC antagonists that are designed, synthesized and evaluated in an effort to develop diversified analogues based on the scaffold of the previously identified high-throughput (HTS) hit ESI-09.

First claim

The invention claimed is:

1. An Exchange Protein Activated by cAMP (EPAC) antagonist
selected from N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-oxo-2-(5-(4-(tert-butyl)phenyl)isoxazol-3-yl)acetohydrazonoyl cyanide (NY0617), N-(3-trifluromethyl-4-chlorophenyl)-2-oxo-2-(5-phenylisoxazol-3-yl)acetohydrazonoyl cyanide (NY0460), N-(3,5-Bis(trifluoromethyl)phenyl)-2-oxo-2-(5-phenylisoxazol-3-yl)acetohydrazonoyl cyanide (NY0457), N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-oxo-2-(5-(4-methoxyphenyl)isoxazol-3-yl)acetohydrazonoyl cyanide (NY0654), N-(3,5-bis(trifluoromethyl)phenyl)-2-(5-(4-methoxyphenyl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide (NY0655), N-(3-Chloro-5-(trifluoromethyl)phenyl)-2-(5-(furan-2-yl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide (NY0725), N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-(5-(furan-2-yl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide (NY0726), or N-(3-Chloro-4-(trifluoromethyl)phenyl)-2-(5-(4-fluorophenyl)isoxazol-3-yl)-2-oxoacetohydrazonoyl cyanide (NY0541).

2. An Exchange Protein Activated by cAMP (EPAC) antagonist having a formula of:

where R 7 and R 11 are H;
R 8 , R 9 , and R 10 are independently selected from H, halogen, CF 3 , C1 to C4 alkyl, C1 to C4 heteroalkyl, or C1 to C4 alkoxy.

3. The compound of claim 2 , wherein R 8 , R 9 , R 10 are independently selected from H, chloro, fluoro, or trifluoromethyl.

4. The compound of claim 2 , wherein the compound is selected from 2-(benzo[d]isoxazol-3-yl)-N-(3-chloro-5-(trifluoromethyl)phenyl)-2-oxoacetohydrazonoyl cyanide (NY0495), 2-(benzo[d]isoxazol-3-yl)-N-(3-chloro-4-(trifluoromethyl)phenyl)-2-oxoacetohydrazonoyl cyanide (NY0561), or 2-(benzo[d]isoxazol-3-yl)-N-(4-chloro-3-(trifluoromethyl)phenyl)-2-oxoacetohydrazonoyl cyanide (NY0562).

5. A method of suppressing a microbe infection comprising administering an EPAC specific inhibitor of claim 1 to a subject having or under the risk of a microbe infection.

6. The method of claim 5 , wherein the microbe is a bacteria, virus, or fungi.

7. The method of claim 5 , wherein the microbe is a bacteria.

8. The method of claim 5 , wherein the microbe is a rickettsia bacteria.

Assignees

• Zhou Jia
• Liu Zhiqing
• Ye Na
• Mei Fang
• Cheng Xiaodong
• Univ Texas

Inventors

• Zhou Jia
• Liu Zhiqing
• Ye Na
• Mei Fang
• Cheng Xiaodong

Classifications

• C07D261/20

  condensed with carbocyclic rings or ring systems · CPC title

• A61K31/423

  condensed with carbocyclic rings · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07C2602/10

  the other ring being six-membered, e.g. tetraline · CPC title

• C07C255/66

  having cyano groups and nitrogen atoms being part of hydrazine or hydrazone groups bound to the same carbon skeleton · CPC title