کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10590795 | 981724 | 2014 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Deuteration and fluorination of 1,3-bis(2-phenylethyl)pyrimidine-2,4,6(1H,3H,5H)-trione to improve its pharmacokinetic properties
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کلمات کلیدی
ADMEamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکamyotrophic lateral sclerosis (ALS) - اسکلروز جانبی جانبی آمیوتروفیک (ALS)ALS - بیماری اسکلروز جانبی آمیوتروفیکDeuteration - تعطیلاتabsorption, distribution, metabolism, excretion - جذب، توزیع، متابولیسم، دفعPharmacokinetics - فارماکوکینتیکFluorination - فلوراسیون
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 21, 1 November 2014, Pages 5098-5101
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 21, 1 November 2014, Pages 5098-5101
نویسندگان
Guoyao Xia, Radhia Benmohamed, Richard I. Morimoto, Donald R. Kirsch, Richard B. Silverman,