Augmenting moieties for anti-inflammatory compounds

Patent metadata

Field	Value
Publication number	US-9512068-B2
Application number	US-201414776857-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

Augmented or synergized anti-inflammatory constructs are disclosed including terpenes covalently conjugated with other anti-inflammatory molecules such as nonsteroidal anti-inflammatory drugs, vanilloids, amino acids and polyamines; and anti-inflammatory molecules covalently conjugated with specific amino acids. For the latter, further conjugation with a choline bioisostere further augments the anti-inflammatory activity.

First claim

What is claimed is:

1. An anti-inflammatory conjugate having the structure of:
vanilloid-(carbamate)-polyamine-(carbamate)-vanilloid, or  Formula 2A,

terpene-(carbamate)-polyamine-(carbamate)-terpene,   Formula 4A,

wherein said terpenes of Formula 4A, are independently selected from the group consisting of thymol, carvacrol, menthol, geraniol, nerol, farnesol and perillyl alcohol;
wherein said polyamine of Formula 2A and 4A is selected from the group consisting of putrescine, spermidine and spermine; and
wherein said vanilloids of Formula 2A, are independently selected from the group consisting of zingerone, eugenol, vanillyl alcohol, 3-methoxy-4-acetyloxybenzyl alcohol, and vanillylamine.

2. The conjugate of claim 1 , Formula 4A, wherein said terpenes are the same terpene.

3. The conjugate of claim 1 , Formula 4A, wherein said terpenes are different terpenes.

4. The conjugate of claim 1 , Formula 2A, wherein said vanilloids are the same vanilloid.

5. The conjugate of claim 1 , Formula 2A, wherein said vanilloids are different vanilloids.

6. A method of increasing the potency of an anti-inflammatory compound, comprising conjugating said anti-inflammatory compound with another anti-inflammatory compound via a carbamate linkage to produce a conjugate, wherein the structure of the conjugate is selected from the group consisting of Formulae 2A and 4A:
vanilloid-(carbamate)-polyamine-(carbamate)-vanilloid, or  Formula 2A,

terpene-(carbamate)-polyamine-(carbamate)-terpene,  Formula 4A,

wherein said terpenes of Formula 4A, are independently selected from the group consisting of thymol, carvacrol, menthol, geraniol, nerol, farnesol and perillyl alcohol;
wherein said polyamine of Formula 2A and 4A is selected from the group consisting of putrescine, spermidine and spermine; and
wherein said vanilloids of Formula 2A, are independently selected from the group consisting of zingerone, eugenol, vanillyl alcohol, 3-methoxy-4-acetyloxybenzyl alcohol, and vanillylamine.

7. The method of claim 6 , comprising two terpenes which are the same.

8. The method of claim 6 , comprising two terpenes which are different.

9. The method of claim 6 , comprising two vanilloids which are the same.

10. The method of claim 6 , comprising two vanilloids which are different.

Assignees

• Univ Rutgers
• Univ Lehigh

Inventors

• Laskin Jeffrey D
• Heindel Ned D
• Heck Diane E
• Lacey Carl Jeffrey
• Young Sherri C

Classifications

• C07C271/22

  to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title

• C07C271/48

  to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K31/405

  Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin · CPC title

• C07C271/50

  to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms · CPC title