No- and H2S-releasing compounds

• US 9,688,607 B2
• Filed: 08/15/2012
• Issued: 06/27/2017
• Est. Priority Date: 08/15/2011
• Status: Active Grant

• Current Assignee: City College of New York
• Original Assignee: City College of New York
• Inventors: Kashfi, Khosrow, Kodela, Ravinder
• Primary Examiner(s): Yu, Misook
• Assistant Examiner(s): Akhoon, Kauser
• Application Number:
  US13/981,378
• Publication Number:
  US 20140221316A1
• Time in Patent Office: 1,777 Days
• Field of Search: None
• CPC Class Codes: A61K 31/655 Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
• 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: C07C 203/04 having nitrate groups bound to acyclic carbon atoms
• CPC Class Codes: C07C 327/48 having carbon atoms of thiocarboxamide groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 331/28 having isothiocyanate groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07D 271/08 1,2,5-Oxadiazoles; Hydrogenated 1,2,5-oxadiazoles
• CPC Class Codes: C07D 339/04 having the hetero atoms in positions 1 and 2, e.g. lipoic acid
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07F 9/65583 each of the hetero rings containing nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/6578 having phosphorus and sulfur atoms with or without oxygen atoms, as ring hetero atoms

Abstract

This disclosure relates to novel compounds containing an H₂S releasing moiety and a nitric oxide (NO) releasing moiety covalently linked with a core (e.g., a salicylic acid moiety) and the use of such compounds in treating inflammatory diseases, including cancers. Therapeutic potency of these compounds is significantly higher than NSAIDs containing a H₂S-releasing moiety alone (HS-NSAIDs) and NSAID containing a NO-releasing moiety alone (NO-NSAIDs). The compounds, in addition, exhibit reduced side effect, e.g., reduced stomach ulcers, upon administration.

Claims

1. A method of treating an inflammatory disease, comprising administering to a subject in need thereof an effective amount of a compound of formula (Ia):

2. The method of claim 1, wherein the inflammatory disease is cancer, rheumatoid arthritis, intestine inflammation, stomach ulcer, a cardiovascular disease, or a neurodegenerative disease.

3. A pharmaceutical composition comprising a compound according to formula (Ia) and a pharmaceutically acceptable excipient, wherein formula (Ia) is represented by the following:

4. A compound of formula (Ia):

5. A compound having the formula: