Synthesis of 13 C6 -labeled, dual-target inhibitor of cannabinoid-1 receptor (CB1 R) and inducible nitric oxide synthase (iNOS).
Malliga R IyerResat CinarNathan J CoffeyGeorge KunosPublished in: Journal of labelled compounds & radiopharmaceuticals (2018)
Cannabinoid-1 receptor (CB1 R) antagonists/inverse agonists have great potential in the treatment of metabolic disorders like dyslipidemia, type 2 diabetes, and nonalcoholic steatohepatitis. Cannabinoid-1 receptor inverse agonists have also been reported to be effective in mitigating fibrotic disorders in murine models. Inducible nitric oxide synthase is another promising target implicated in fibrotic and inflammatory disorders. We have disclosed MRI-1867 as a potent and selective, peripherally acting dual-target inhibitor of the CB1 R and inducible nitric oxide synthase (iNOS). Herein, we report the synthesis of [13 C6 ]-MRI-1867 as a racemate from commercially available chlorobenzene-13 C6 as the starting, stable-isotope label reagent. The racemic [13 C6 ]-MRI-1867 was further processed to the stable-isotope-labeled enantiopure compounds using chiral chromatography. Both racemic [13 C6 ]-MRI-1867 and S-13 C6 -MRI-1867 will be used to quantitate unlabeled S-MRI-1867 during clinical drug metabolism and pharmacokinetics studies and will be used as a liquid chromatography-tandem mass spectrometry bioanalytical standard.
Keyphrases
- nitric oxide synthase
- nitric oxide
- contrast enhanced
- magnetic resonance imaging
- type diabetes
- diffusion weighted imaging
- liquid chromatography tandem mass spectrometry
- computed tomography
- oxidative stress
- magnetic resonance
- simultaneous determination
- ms ms
- high resolution
- pet imaging
- skeletal muscle
- idiopathic pulmonary fibrosis
- ionic liquid
- metabolic syndrome
- insulin resistance
- positron emission tomography