Unknown

Dataset Information

0

Deuteration and fluorination of 1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione to improve its pharmacokinetic properties.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and death, most often from respiratory failure. Over 200 pyrimidine-2,4,6-trione (PYT) small molecules, which prevent aggregation and reduce the associated toxicity of mutant superoxide dismutase 1 (SOD1) found in patients with familial ALS, have been synthesized and tested. One of the compounds (1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione, (1) was previously found to have an excellent combination of potency efficacy, and some desirable pharmacokinetic properties. To improve the solubility and metabolic stability properties of this compound, deuterium and fluorine were introduced into 1. New analogs with better solubility, plasma stability, and human microsome stability were identified.

SUBMITTER: Xia G 

PROVIDER: S-EPMC4250310 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Deuteration and fluorination of 1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione to improve its pharmacokinetic properties.

Xia Guoyao G   Benmohamed Radhia R   Morimoto Richard I RI   Kirsch Donald R DR   Silverman Richard B RB  

Bioorganic & medicinal chemistry letters 20140915 21

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and death, most often from respiratory failure. Over 200 pyrimidine-2,4,6-trione (PYT) small molecules, which prevent aggregation and reduce the associated toxicity of mutant superoxide dismutase 1 (SOD1) found in patients with familial ALS, have been synthesized and tested. One of the compounds (1,3-bis(2-phenylethyl)pyrimidine-2  ...[more]

Similar Datasets

Unknown 1,3-Dimethyl-5-(2-methyl-benzyl-idene)pyrimidine-2,4,6(1H,3H,5H)-trione.
| S-EPMC2970469 | biostudies-literature
Unknown 5-[1-(1,3-Dimethyl-2,4,6-trioxohexa-hydropyrimidin-5-yl)-2-oxoprop-yl]-1,3-di-methyl-pyrimidine-2,4,6(1H,3H,5H)-trione.
| S-EPMC3793818 | biostudies-other
Unknown Crystal structure of 5,5-bis-(4-methyl-benz-yl)pyrimidine-2,4,6(1H,3H,5H)-trione monohydrate.
| S-EPMC4331871 | biostudies-literature
Unknown Crystal structure of 5-[bis-(methyl-sulfon-yl)meth-yl]-1,3-dimethyl-5-(methyl-sulfon-yl)pyrimidine-2,4,6(1H,3H,5H)-trione.
| S-EPMC4331903 | biostudies-literature
Unknown Rubidium 2,4,6-trioxo-1,3-diazinan-5-ide-1,3-diazinane-2,4,6-trione-water (1/1/1).
| S-EPMC3089342 | biostudies-literature
Unknown 5-(3,4-Dimeth-oxy-benzyl-idene)-1,3-dimethyl-1,3-diazinane-2,4,6-trione.
| S-EPMC3254518 | biostudies-literature
Unknown Design, synthesis, and discovery of 5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and related derivatives as novel inhibitors of mPGES-1.
| S-EPMC5836806 | biostudies-literature
Unknown 1,3-Dibenzyl-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.
| S-EPMC3089129 | biostudies-literature
Unknown 1,3-Diallyl-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.
| S-EPMC3007069 | biostudies-literature
Unknown 1,3-Bis[3-(1,3-dioxoisoindolin-2-yl)prop-yl]-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.
| S-EPMC3213577 | biostudies-literature