Discovery of 1,3-Disubstituted Pyrazole Peripheral Cannabinoid Receptor Partial Agonists

18 Pages Posted: 8 Mar 2023

See all articles by George Amato

George Amato

RTI International

Scott Runyon

RTI International

Vineetha Vasukuttan

RTI International

Ann M. Decker

RTI International

Elaine A. Gay

RTI International

Lucas Laudermilk

RTI International

Rangan Maitra

RTI International

Abstract

Partial agonists of peripheral cannabinoid receptors (CBRs) have potential therapeutic applications in several medical conditions. However, (−)-trans-Δ9-tetrahydrocannabinol (THC), the principal active component of marijuana, which is a partial agonist of CB1 and CB2 penetrates the central nervous system (CNS) and produces adverse effects. Peripherally restricted partial agonists of CBRs, particularly of CB1, can be used to treat illnesses safely and effectively with a better therapeutic index. Here, we report on our efforts to synthesize pyrazole partial CBR agonists with peripheral selectivity, resulting in lead compound 40. This compound is a potent partial agonist of CB1 with ~5-fold higher plasma biodistribution over brain and represents an early lead for optimization.

Keywords: CB1, Cannabinoid, peripheral, CB2, agonist, compound

Suggested Citation

Amato, George and Runyon, Scott and Vasukuttan, Vineetha and Decker, Ann M. and Gay, Elaine A. and Laudermilk, Lucas and Maitra, Rangan, Discovery of 1,3-Disubstituted Pyrazole Peripheral Cannabinoid Receptor Partial Agonists. Available at SSRN: https://ssrn.com/abstract=4374822 or http://dx.doi.org/10.2139/ssrn.4374822

George Amato

RTI International ( email )

PO Box 12194
Washington, DC 20036-3209
United States

Scott Runyon

RTI International ( email )

PO Box 12194
Washington, DC 20036-3209
United States

Vineetha Vasukuttan

RTI International ( email )

Ann M. Decker

RTI International ( email )

PO Box 12194
Washington, DC 20036-3209
United States

Elaine A. Gay

RTI International ( email )

PO Box 12194
Washington, DC 20036-3209
United States

Lucas Laudermilk

RTI International ( email )

PO Box 12194
Washington, DC 20036-3209
United States

Rangan Maitra (Contact Author)

RTI International ( email )

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