Alimardanov, Asaf (NCATS)
Huang, Junfeng (NCATS)
In the last decade, prescription opioid abuse and misuse has been a major contributor to mortality in the United States, resulting in a serious national public health crisis. Nearly 12 million Americans used prescription opioids nonmedically in 2018, with >67,000 people dying from an opioid overdose.
The federal response to the opioid crisis includes research support toward the development of non-addictive analgesics and additional medications to treat opioid use disorders (OUD). Recently, a novel series of (R)-N-(4-(4-(3-chloro-5-ethyl-2-methoxyphenyl) piperazin-1-yl)-3-hydroxybutyl)-1H-indole-2-carboxamide (8)-(R)VK4-116 have been discovered as high affinity and selective D3R (Dopamine D3 receptor) lead molecules for the treatment of opioid use disorders (OUD) by a discovery team at NIDA (NIH).
Furthering the earlier work by colleagues at NIDA, NCATS scientists have developed new synthetic routes to accelerate synthesis and yields for preclinical and clinical trial studies of (R)-VK4-116.
- Dopamine D3 Antagonist synthesis
- Opioid addiction mitigation
- Reduce severity of opioid addiction withdrawal
- Prevent opioid addiction relapse
- Alternate route for Atorvastatin synthesis
The method describes a novel synthesis method that reduces the number of steps to synthesize selective Dopamine D3 Antagonists, specifically, (R)VK4-116.
- Reduces number of steps in synthesis method from 15 to 7
- Dramatically increases synthesis yield from 1.5% to >48% overall yield
- Eliminates the use of a controlled substance in the synthesis route
- New synthesis route successfully tested in 2 kg GMP Scale up
- Novel synthesis method created novel intermediates useful for other drug synthesis routes