Rutaecarpine analogs and applications thereof

• US 10,526,333 B2
• Filed: 04/13/2018
• Issued: 01/07/2020
• Est. Priority Date: 04/13/2018
• Status: Active Grant

• Current Assignee: Taipei Medical University WAN Fan Hospital (Government of The Republic of China)
• Original Assignee: Taipei Medical University WAN Fan Hospital (Government of The Republic of China)
• Inventors: Lin, Chun-Mao, Lee, Chi-Ming, Wang, Chi, Huang, Sheng-Tung, Gu, Jiun-An, Rau, Tin-An
• Primary Examiner(s): Pagano, Alexander R
• Assistant Examiner(s): Sackey, Ebenezer O
• Application Number:
  US15/952,644
• Publication Number:
  US 20190315746A1
• Time in Patent Office: 634 Days
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07D 471/14 Ortho-condensed systems

Abstract

The present invention provides RUT analogs with various biological activities. In particular, the biological activities comprise anti-inflammatory activity, vasodilator effects, migration/invasion-suppressive activities, ability against damage due to remodeling between the epithelium and endothelium, collagen deposition and cardiac fibrosis suppress, Snail protein inhibitory effect, etc., which may improve cardiac, vasodilation, and lung functions. The RUT analogs disclosed herein also exhibit a lower cytotoxicity comparing to RUT.

Claims

1. A compound having the following Formula (I),

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

3. The compound of claim 2, wherein R₃, R₄, and R₅ are each H.

4. The compound of claim 3, wherein R₁ and R₂ each are H.

5. The compound of claim 1, wherein R is H.

6. The compound of claim 5, wherein R₃, R₄, and R₅ are each H.

7. The compound of claim 6, wherein R₁ and R₂ each are H.

8. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable ester, salt, or prodrug thereof, together with a pharmaceutically acceptable carrier.

9. A method of ameliorating inflammation in a subject, comprising a step of administering a compound of claim 1 to the subject.

10. A method of ameliorating damage due to remodeling between the epithelium and endothelium in a subject, comprising a step of administering a compound of claim 1 to the subject.

11. A compound of 10-fluoro-2-methoxyrutaecarpine (F-RUT).

12. A compound of 10-fluoro-2,3-dimethoxyrutaecarpine.