Synthesis of a delta opioid agonist in [2H6], [2H4], [11C], and [14C] labeled forms

Elmore, Charles S.; Brush, Kelly; Schou, Magnus; Palmer, William E.; Dorff, Peter N.; Powell, Mark; Hoesch, Valerie; Hall, James Edwin; Hudzik, Thomas J.; Halldin, Christer; Dantzman, Cathy L.

doi:10.1002/jlcr.1939

Cited by 8 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2011, Elmore and co-workers at AstraZeneca published the synthesis of a delta opioid agonist ( 15 ) based on a palladium-catalyzed amino-carbonylation as the final step (Scheme , top). In this procedure, [ 14 C]CO was produced by [ 14 C] sodium formate dehydration after the addition of sulfuric acid at 110 °C . The same strategy was used for a series of other carbonylations from aryl halides, such as hydroxycarbonylations, , alkoxycarbonylations, and intramolecular aminocarbonylations …”

Section: Radiocarbon Labelingmentioning

confidence: 99%

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

Babin

Taran

2022

JACS Au

View full text Add to dashboard Cite

Carbon-14 ( 14 C) is a gold standard technology routinely utilized in pharmaceutical and agrochemical industries for tracking synthetic organic molecules and providing their metabolic and safety profiles. While the state of the art has been dominated for decades by traditional multistep synthetic approaches, the recent emergence of late-stage carbon isotope labeling has provided new avenues to rapidly access carbon-14-labeled biologically relevant compounds. In particular, the development of carbon isotope exchange has represented a fundamental paradigm change, opening the way to unexplored synthetic transformations. In this Perspective, we discuss the recent developments in the field with a critical assessment of the literature. We subsequently discuss research directions and future challenges within this rapidly evolving field.

show abstract

Section: Radiocarbon Labelingmentioning

confidence: 99%

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

Babin

Taran

2022

JACS Au

View full text Add to dashboard Cite

show abstract

“…In general, all tested palladium‐catalyzed aminocarbonylations worked well, and all target tricyclic cores (compounds 167 , 169 , and 171 ) were obtained in yields ranging from 36% to 52% based on the aromatic halides as the limiting reagents (compounds 166 , 168 , and 170 ). Finally, Elmore and coworkers applied their [ 14 C]CO generator when metabolic studies required the 14 C‐labeling of the delta opioid agonist 173 depicted in Scheme . Having already developed the method (discussed above in Scheme ), 173 was secured in a good 34% isolated yield from 172 (22% RCY), again as the final step in the linear synthesis.…”

Section: Carbonylation Using [14c ]Comentioning

confidence: 99%

Recent developments in carbonylation chemistry using [¹³C]CO, [¹¹C]CO, and [¹⁴C]CO

Nielsen

Neumann

Lindhardt

et al. 2018

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

Carbon monoxide represents the most important C1-building block for the chemical industry, both for the production of bulk and fine chemicals, but also for synthetic fuels. Yet its toxicity and subsequently its cautious handling have limited its applications in medicinal chemistry research and in particular for the synthesis of pharmaceutically relevant molecules. Recent years have nevertheless witnessed a considerable headway on the development of carbon monoxide surrogates and reactor systems, which provide an ideal setting for performing carbonylation chemistry with stoichiometric and substoichiometric carbon monoxide. Such setups are particularly ideal for the introduction of isotope labels such as carbon-11, carbon-13, and carbon-14 into bioactive compounds. This review summarizes this growing field and examines the large number of carbonylation reactions that can be exploited for the introduction of a carbon isotope.

show abstract

“…A better understanding of the DOR pharmacology (i.e. subtype and expression level of DORs) within a certain circuit may also lead to design and synthesis of better/more (subtype-) selective fluorescent DOR probes and PET ligands (Clayson et al 2001; Elmore et al 2011) to investigate DOR function specifically within this circuit.…”

Section: Future Prospects For the Development Of Dor Selective Drumentioning

confidence: 99%

Pharmacological traits of delta opioid receptors: pitfalls or opportunities?

2013

View full text Add to dashboard Cite

Delta opioid receptors (DORs) have been considered as a potential target to relieve pain as well as treat depression and anxiety disorders, and are known to modulate other physiological responses, including ethanol and food consumption. A small number of DOR selective drugs are in clinical trials, but no DOR selective drugs have been approved by the Federal Drug Administration and some candidates have failed in phase II clinical trials, highlighting current difficulties producing effective delta opioid based therapies. Recent studies have provided new insights into the pharmacology of the DOR, which is often complex and at times paradoxical. This review will discuss the existing literature focusing on four aspects: 1) Two DOR subtypes have been postulated based on differences in pharmacological effects of existing DOR-selective ligands 2) DORs are expressed ubiquitously throughout the body and central nervous system and are, thus, positioned to play a role in a multitude of diseases. 3) DOR expression is often dynamic, with many reports of increased expression during exposure to chronic stimuli, such as stress, inflammation, neuropathy, morphine, or changes in endogenous opioid tone. 4) A large structural variety in DOR ligands implies potential different mechanisms of activating the receptor. These combined features of DOR pharmacology illustrate the potential benefit of designing tailored or biased DOR ligands.

show abstract

Synthesis of a delta opioid agonist in [²H₆], [²H₄], [¹¹C], and [¹⁴C] labeled forms

Abstract: In support of a program to develop a treatment for depression, four labeled forms of a delta opioid agonist were prepared.

Cited by 8 publications

References 14 publications

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

Recent developments in carbonylation chemistry using [¹³C]CO, [¹¹C]CO, and [¹⁴C]CO

Pharmacological traits of delta opioid receptors: pitfalls or opportunities?

Contact Info

Product

Resources

About

Synthesis of a delta opioid agonist in [2H6], [2H4], [11C], and [14C] labeled forms

Abstract: In support of a program to develop a treatment for depression, four labeled forms of a delta opioid agonist were prepared.

Cited by 8 publications

References 14 publications

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

Recent developments in carbonylation chemistry using [13C]CO, [11C]CO, and [14C]CO

Pharmacological traits of delta opioid receptors: pitfalls or opportunities?

Contact Info

Product

Resources

About

Synthesis of a delta opioid agonist in [²H₆], [²H₄], [¹¹C], and [¹⁴C] labeled forms

Recent developments in carbonylation chemistry using [¹³C]CO, [¹¹C]CO, and [¹⁴C]CO