Cannabinoid conjugate molecules

Inventors

HERSHBERGER, Paul M. • LIU, Yinghui • HERING, KIRK WILLIAM • Kramer, James Bernard • Lalgudi, Ramanathan S.

Assignees

Enveric Biosciences Inc • Akos Biosciences Inc

Abstract

Disclosed are conjugate molecules formed from an active agent which is linked to a cannabinoid moiety through a specified linker having ester and amide end groups. The active agent can be a COX-2 inhibitor moiety, and the cannabinoid moiety can be a cannabidiol moiety. These conjugate molecules are contemplated to potentially be effective in the treatment of medical conditions.

Core Innovation

The disclosed subject matter relates to cannabinoid-active agent conjugate molecules in which an active agent molecule, specifically a COX-2 inhibitor molecule such as celecoxib, is linked to a cannabinoid moiety, notably a CBD moiety. The conjugate molecules are provided as defined structural forms, including Formula (I), Formula (L-1), Formula (I-a), Formula (II), Formula (II-a), Formula (III-a)/(III-b), and Formula (IV-a) to Formula (IV-c), with definitions of linker and substituents. The linker includes an ester end group and an amide end group as part of the conjugate architecture.

A central structural concept is the covalent linkage between the celecoxib molecule and the cannabinoid moiety through a defined linker that bears ester and amide end groups, yielding a conjugate molecule having the structure of Formula (II). The active agent moiety is described using a list of eligible COX-2 inhibitor moieties, and the cannabinoid moiety set includes cannabinoid derivatives such as cannabidiol (CBD) and related cannabinoid compounds and derivatives, including acetylated derivatives and alkylated/methylated/salt forms of CBD derivatives CM-1 to CM-5. The description also includes celecoxib-CBD conjugates as representative examples.

The disclosed synthesis concept uses an aminohydroxyalkane having a protecting group on the amino group, reacting with a celecoxib molecule to form a covalent bond and obtain a second intermediate molecule. The protecting group on the amino group is removed to obtain a primary intermediate molecule comprising the celecoxib molecule, and this primary intermediate is coupled with a secondary intermediate molecule comprising a cannabinoid having a chloroformate group to obtain the conjugate molecule with the structure of Formula (II). Example embodiments describe making specific celecoxib-CBD conjugates and include comparative unsuccessful syntheses.

Claims Coverage

The independent claim in the partial content is clm-00001. It defines a complete synthetic method for a celecoxib-cannabinoid conjugate having the structure of Formula (II), including the preparation of both a celecoxib-containing primary intermediate and a chloroformate-bearing cannabinoid secondary intermediate, followed by coupling to produce the conjugate. The dependents refine the structural parameters of the linker and substituents and further constrain preparation of the secondary cannabinoid intermediate via named CBD protection and optional deprotection.

Across the independent claim and dependents, the claimed inventive subject matter centers on constructing a celecoxib-cannabinoid conjugate of Formula (II) via protected aminohydroxyalkane formation of a celecoxib intermediate, followed by coupling to a cannabinoid chloroformate-bearing intermediate. Dependent claims refine the linker length (L), constrain the identity of R, specify a Formula (II-a) variant, and optionally further refine secondary intermediate preparation through CBD hydroxyl protection using TBDPSCl and possible removal of the TBDPS protecting group.

Stated Advantages

Documented Applications