Alexander Grenning

Systematically Provides a Diverse Array of Polycyclic Terpene Cores for Use in Drug Design and Development

Structurally complex terpenoid compounds provide access to a wide assortment of potential biological functions that can be exploited to develop pharmaceutical therapies. Despite recent efforts to increase efficiency within the pharmaceutical research and development sector, drug discovery is still an extensive, costly, and inefficient process, which maintains a low rate of new therapeutic discovery. Approximately one in every 5,000 compounds that reach the preclinical testing stage becomes an approved drug in the United States, and costs average nearly $2.6 billion to develop a drug over a 10-year period. The systems in place for drug discovery and design are in need of increased efficiency, which could be achieved through systematic production of chemical compounds for initial testing phases. Researchers at the University of Florida have developed a simple and scalable strategy to synthesize diverse arrays of compounds containing polycyclic terpene cores, which increases drug discovery efficiency and simplifies early-stage development of therapeutic agents. This uncomplicated approach uses inexpensive and abundantly available reagents, lowering costs associated with ongoing drug discovery and design efforts throughout the pharmaceutical industry.

Application

Systematic synthesis of terpenoid compounds for drug design and development.

Advantages

• Utilizes simple and scalable synthesis process, increasing efficiency and allowing robust production of diverse terpenoid compounds
• Employs inexpensive, widely-available chemical reagents, lowering costs and simplifying early stages of drug design and development
• Combines abundantly available chemical reagents in a simple manner, enabling systematic construction of unique terpene-based compounds

Technology

This synthesis strategy uses inexpensive and abundantly available Knoevenagel adducts (cycloalkanones + malonitrile) and allylic electrophiles to systematically generate a diverse array of terpenoid natural product scaffolds with wide-ranging potential biological activities. The process uses three known chemical reactions, allowing the user to manipulate functional groups present on the final polycycloalkane compounds. The strategy is highly tunable, encouraging development of complex molecular structures with a high yield and without need for extensive optimization. This increase in molecular malleability will enable countless drug discovery and development efforts.

Achieves the Bioactivity of THC with Improved Stability and Pharmaceutical Properties

These cannabinol analogues formulate analgesic drugs as an alternative to opioid medications. Due to the United States’ opioid crisis, many researchers investigate cannabinoid compounds as potential alternatives for pain management. An ongoing challenge in cannabinoid drug development is the instability of the tetrahydrocannabinol (THC) oxidation state, which causes it to oxidize easily into its less bioactive cannabinol (CBN) counterparts. Axially-chiral cannabinol (ax-CBN) compounds would have similar biological profiles to THC with improved stability and drug-like properties. Unfortunately, easy and effective synthetic methods to prepare ax-CBN compounds do not exist.

Researchers at the University of Florida have developed substituted axially-chiral cannabinol analogues with increased stability that are suitable for non-opioid pain management. These ax-CBN compounds can form pharmaceuticals to treat diseases, such as Huntington’s disease, epilepsy, arthritis, or inflammation-related conditions.

Application

Analgesic drugs that use cannabinol analogues with greater stability than THC

Advantages

• Possess inherent biological activity and pharmaceutical stability, making them more reliable than THC in analgesic drugs
• Features an easy synthesis process, making cannabinol analogues a strong alternative to opioids for managing pain

Technology

These axially-chiral cannabinols (ax-CBNs) have biological activity comparable to tetrahydrocannabinols (THCs) but with better stability and pharmaceutical properties. The conventional route for preparing cannabinoid analogs relies on coupling an appropriate monoterpene with a resorcinol derivative. Cannabinoids like THC oxidize easily and, therefore, lose bioactivity, making it difficult to develop them into drugs. The ax-CBNs have a methyl group attached to the cannabinol ring located on the C10 carbon, which locks in the axially-chiral component. An easy synthesis process allows ax-CBN compounds to function as non-opioid alternative analgesics.