Biologically active cannabidiol analogs

Patent metadata

Field	Value
Publication number	US-10709681-B2
Application number	US-201716073766-A
Country	US
Kind code	B2
Filing date	Jan 27, 2017
Priority date	Jan 29, 2016
Publication date	Jul 14, 2020
Grant date	Jul 14, 2020

Abstract

Biologically active cannabidiol analogs comprising a compound of the formula

wherein one of R 1 or R 2 or both is/are the residue of a moiety formed by the reaction of an amino group of the amino acid ester of R 1 or R 2 or both with a dicarboxylic acid or a dicarboxylic acid derivative and the other R 1 or R 2 (in the case of the mono) is the residue of a dicarboxylic acid or dicarboxylic acid derivative or Hydrogen (H), (i.e. underivatized), and salts thereof. These CBD analogs are be useful in pain management in oncology and other clinical settings in which neuropathy is presented. Furthermore, these CBD-analogs are useful in blocking the addictive properties of opiates.

First claim

What we claim is:

1. A biologically active cannabidiol analog of the formula I

wherein one of R 1 or R 2 is H and the other is an amino acid ester amide or both R 1 and R 2 are an amino acid ester amide; or one of R 1 or R 2 is the amino acid ester amide and the other R 1 or R 2 is the ester residue of a dicarboxylic acid or dicarboxylic acid halide; wherein the amino acid ester amide comprises an amino acid linked to one or both of the hydroxyl groups of cannabidiol through an ester linkage and a dicarboxylic acid or dicarboxylic acid halide to the amino group of the amino acid in an amide linkage, wherein the amino acid is one of Alanine, Arginine, Asparagine, Aspartic Acid, Cysteine, Glutamine, Glutamic Acid, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine and Valine, and a pharmaceutically acceptable salt thereof.

2. The biologically active cannabidiol analog of claim 1 , wherein the dicarboxylic acid is an organic compound containing two carboxyl functional groups having the formula HO 2 C—R—CO 2 H, where R is a straight chain or branched aliphatic or aromatic lower alkyl.

3. The analog of claim 1 , wherein the compound is CBD-Di-Alaninate-Di-Hemisuccinate, CBD-Divalinate-Di-Hemisuccinate, CBD-Mono-Valinate-Mono-Hemisuccinate, or CBD-monovalinate-dihemisuccinate.

4. A biologically active cannabidiol analog of claim 1 which is CBD-Divalinate-Di-Hemisuccinate, having the formula

5. A biologically active cannabidiol analog of claim 1 which is CBD-Monovalinate-Di-Hemisuccinate, having the formula

6. A biologically active cannabidiol analog of claim 1 which is CBD-Monovalinate-Mono-Hemisuccinate, having the formula

7. A pharmaceutical composition comprising the biologically active cannabidiol analog of claim 1 in a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising the biologically active cannabidiol analog of claim 3 in a pharmaceutically acceptable carrier.

9. The biologically active cannabidiol analog of claim 1 , wherein the dicarboxylic acid is malonic acid, malic acid, glutaric acid, succinic acid, and phthalic acid.

10. A pharmaceutical composition comprising the biologically active cannabidiol analog of claim 6 in a pharmaceutically acceptable carrier.

11. A biologically active cannabidiol analog of the formula I

wherein one of R 1 or R 2 is H and the other is an amino acid ester amide, wherein the amino acid ester amide comprises an amino acid linked to one of the hydroxyl groups of cannabidiol through an ester linkage and a dicarboxylic acid or dicarboxylic acid halide to the amino group of the amino acid in an amide linkage wherein the amino acid is one of Alanine, Arginine, Asparagine, Aspartic Acid, Cysteine, Glutamine, Glutamic Acid, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine and Valine, and a pharmaceutically acceptable salt thereof.

12. The biologically active cannabidiol analogs of claim 11 , wherein the dicarboxylic acid is an organic compound containing two carboxyl functional groups having the formula HO 2 C—R—CO 2 H, where R is a straight chain or branched aliphatic or aromatic lower alkyl.

13. The compound of claim 11 , wherein the compound is CBD-Mono-Valinate-Mono-Hemisuccinate.

14. The compound of claim 11 , which is CBD-Divalinate-Di-Hemisuccinate, having the formula

15. A pharmaceutical composition comprising the biologically active cannabidiol analog of claim 11 in a pharmaceutically acceptable carrier.

16. The biologically active cannabidiol analog of claim 11 , wherein the dicarboxylic acid is malonic acid, malic acid, glutaric acid, succinic acid, and phthalic acid.

17. A pharmaceutical composition comprising the biologically active cannabidiol analog of claim 3 in a pharmaceutically acceptable carrier.

Assignees

• Univ Mississippi

Inventors

• Elsohly Mahmoud A
• Majumdar Soumyajit
• Gul Waseem
• Ashfaq Mohammad Khalid
• Sufka Kenneth Joseph
• Harris Hannah Marie

Classifications

• A61K31/223 Primary

  of alpha-aminoacids · CPC title

• A61K31/658

  o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol · CPC title

• C07C2601/16

  the ring being unsaturated · CPC title

• C07C237/20 Primary

  the carbon skeleton containing six-membered aromatic rings · CPC title

• C07C237/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title