Cannabinergic nitrate esters and related analogs

Patent metadata

Field	Value
Publication number	US-10968206-B2
Application number	US-201916240190-A
Country	US
Kind code	B2
Filing date	Jan 4, 2019
Priority date	Feb 26, 2013
Publication date	Apr 6, 2021
Grant date	Apr 6, 2021

Abstract

The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders.

First claim

What is claimed is:

1. A compound of formula (IIa):

or a pharmaceutically acceptable salt thereof;
wherein:
ring C is carbocyclic, bicyclic, aryl, heterocyclyl, heteroaryl, or a terpene;
G is a bond, C═O, NH, CH 2 , CONN, NHCO, C(O)O, OC(O), OCH 2 , S, SO, SO 2 , or O;
ring A is:

R 2a and R 2b are each independently H, OH, SH, NH 2 , CF 3 , COOH, alkoxy, halogen, ONO 2 , alkyl-ONO 2 , or optionally substituted alkyl, haloalkyl, amine, amide, imide, alkoxy, alkoxy thio, phosphate, phosphonate, carboxyl, formyl, carbamyl, amino, acylamino, amido, imido, aminoalkyl, aminoaryl, heteroarylamino, heterocyclylamino, sulfonate, sulfonamide, sulfonyl, thioalkyl, thioaryl, heteroarylthio, heterocyclylthio, phosphonate, phosphate, or acetate;
Y is a bond; and
R 3 is alkyl,
wherein the carbocyclic, bicyclic, aryl, heterocyclyl, or heteroaryl Ring C is optionally substituted with one or more substituents selected from alkyl, alkynyl, alkenyl, alcohol, halogen, hydroxyl, alkoxy, alkenoxy, alkynoxy, aryloxy, aralkyloxy, heterocyclyloxy, heterocyclylalkoxy, oxo, carboxyl, ester, urethane, oxime, hydroxylamine, alkoxyamine, aralkoxyamine, thiol, sulfide, sulfoxide, sulfone, sulfonyl, sulfonamide, amine, N-oxide, hydrazine, hydrazide, hydrazine, azide, amide, urea, amidine, guanidine, enamine, imide, isocyanate, isothiocyanate, cyanate, thiocyanate, imine, nitro, or nitrile.

2. The compound of claim 1 , wherein ring C is:

3. The compound of claim 1 , wherein:
ring C is carbocyclic or heterocyclyl;
ring A is heteroaromatic;
G is C═O or CONH; and
R 2a and R 2b are each independently Cl, OH, O-alkyl, alkyl, amino, thio, O(CO)alkyl, or OC(O)NH 2 .

4. The compound of claim 1 , wherein:
C is aromatic and A is heteroaromatic, and G is C═O;
C is aromatic and A is heteroaromatic, and G is CONH;
C is heterocyclic and A is heteroaromatic, and G is C═O;
C is carbocyclic and A is heteroaromatic, and G is C═O;
C is aromatic and A is heteroaromatic, and G is NH;
C is a terpene;
C is carbocyclic;
C is heteroaromatic and A is heteroaromatic, and G is OCH 2 ;
C is aromatic and A is heterocyclic, and G is CH 2 ;
C is carbocyclic and A is heteroaromatic, and G is a COO or OCO;
C is heterocyclic and A is heteroaromatic, and G is a bond;
C is aromatic and A is heterocyclic, and G is a bond; or
C is bicyclic.

5. A compound represented by one of the following structural formulas:

or a pharmaceutically acceptable salt thereof.

6. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

7. A compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein ring A is:

Assignees

• Univ Northeastern

Inventors

• Makriyannis Alexandros
• Vemuri Venkata Kiran

Classifications

• A61K31/658

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

• C07C203/04

  having nitrate groups bound to acyclic carbon atoms · CPC title

• C07D311/78

  Ring systems having three or more relevant rings · CPC title

• A61K31/435

  having six-membered rings with one nitrogen as the only ring hetero atom · CPC title

• C07C2602/42

  the bicyclo ring system containing seven carbon atoms · CPC title