2,4(1H,3H)-Pyrimidinedione, 5-amino-/4-Amino-2,6-dihydroxypyrimidine/6-Amino-2,4(1H,3H)-pyrimidinedione/2,4(1H,3H)-Pyrimidinedione, 6-amino-/2,4-Dihydroxy-5-aminopyrimidine/5-Amino-2,4-dihydroxypyrimidine/URACIL,5-AMINO/5-aminopyrimidine-2,4(1H,3H)-dione/6-aminopyrimidine-2,4-diol/Pyrimidine, 2,4-dihydroxy-6-amino/5-aminouracyl/2,4-Dihydroxy-6-aminopyrimidine/6-aminopyrimidine-2,4(1H,3H)-dione/5-Amino-2,4-pyrimidinediol/5-Aminouracil/6-Aminouracil/5-Amino-2,4(1H,3H)-pyrimidinedione/5-Amino-1H-pyrimidin-2,4-dion
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The synthesis and reactions of 5-aminouracil and its derivatives are comprehensively reviewed. A brief survey of biological activities, especially chemotherapeutic and pharmacological properties, is also reported.
5-Aminouracil; Chemotherapeutic interest; Pharmacological interest; Reactivity; Synthesis.
Synthesis, Reactivity, and Biological Activity of 5-aminouracil and Its Derivatives
Raafat Mohamed Shaker 1, Mohamed Abd Elrady 2, Kamal Usef Sadek 3
Background: The internet is a source of knowledge and medium widely used in services that facilitate access to information and networking. Multiple sclerosis (MS) patients find the possibility of acquiring information relating to their condition particularly rewarding.
Objective: We aimed to identify Polish MS patients’ preferences by analyzing a percentage of internet users and determining the most common search subjects and patients’ approach to information on the internet. Disability connected with the condition, its duration, and other factors that influence patients’ internet use were examined along with instances of relations established through the internet and their durability.
Methods: The study examined 1045 patients (731 women, 314 men) treated in 10 Polish MS centers, of whom 932 (89.19%) declared to be internet users. Their average age was 40.65 (SD 11.06) and average MS duration was 9.08 (SD 6.97) years. The study used a proprietary survey on information seeking, the range of searched subjects, and internet usage frequency.
Results: The majority of the patients (494/932, 53.0%) used the internet 6-7 times per week and 4.3% (40/932) declared they spent minimum 2 hours per day. The most commonly searched subjects were world news (604/932, 72.9% of patients using the internet); 60.8% (504/932) searched for information on their condition, particularly for new treatment methods (562/932, 67.8%) and the course of illness (520/932, 62.7%). One’s sex had no impact on internet usage (female vs male, odds ratio [OR] 1.13, 95% CI 0.72-1.77), although a patient’s age might, at varying degrees. We found several significant associations using a .05 significance level: a patient with higher education used the internet 9 times more often than one with primary education (OR 8.64, 95% CI 3.31-22.57); lasting relationships increased chances of internet usage by 10-fold compared to widowers (OR 0.12, 95% CI 0.05-0.31); living in a city with a population over 100,000 increased chances by nearly 6 times compared with the countryside (OR 5.59, 95% CI 2.72-11.48); the relapsing-remitting MS type saw a 2-fold increase compared with the primary progressive MS type (OR 0.47, 95% CI 0.29-0.75); and those needing assistance were 2 times less likely to use the internet than patients who could move independently (OR 0.53, 95% CI 0.31-0.89). More than half of the patients (489/932, 52.5%) did not discuss the information found on the internet with their neurologists; 15.9% (148/932) believed that relationships established through the internet can be stable.
Conclusions: The majority of Polish patients use the internet as a crucial information source on their condition and innovative treatment methods. The internet can be helpful in establishing new relationships, which are usually short-lived. Polish patients do not frequently discuss the information gathered on the internet with their doctors.
doctor-patient relationship; information seeking; internet; multiple sclerosis.
Internet Usage by Polish Patients With Multiple Sclerosis: A Multicenter Questionnaire Study
Andrzej Potemkowski # 1, Waldemar Brola # 2, Anna Ratajczak # 3, Marcin Ratajczak # 4, Jacek Zaborski # 5, Elżbieta Jasińska 6, Anna Pokryszko-Dragan # 7, Ewa Gruszka # 7, Marta Dubik-Jezierzańska # 8, Aleksandra Podlecka-Piętowska # 9, Monika Nojszewska # 9, Krystyna Gospodarczyk-Szot # 9, Adam Stępień # 10, Katarzyna Gocyła-Dudar # 10, Marzena Maciagowska-Terela # 10, Jacek Wencel # 11, Radosław Kaźmierski # 11, Alina Kułakowska # 12, Katarzyna Kapica-Topczewska # 12, Witold Pawełczak # 13, Halina Bartosik-Psujek # 14
2019 Feb 1
Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3-500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM). Like native antigens, this antigen preparation induces MR1 refolding and upregulates surface expression of human MR1, forms MR1 tetramers that detect MAIT cells in human PBMCs, and stimulates cytokine expression (IFNγ, TNF) by human MAIT cells. These antigens also induce MAIT cell accumulation in mouse lungs after administration with a co-stimulant. These chemical and immunological findings provide new insights into antigen properties and MAIT cell activation.
Stabilizing Short-Lived Schiff Base Derivatives of 5-aminouracils That Activate Mucosal-Associated Invariant T Cells
Jeffrey Y W Mak 1 2, Weijun Xu 1 2, Robert C Reid 1 2, Alexandra J Corbett 3, Bronwyn S Meehan 3, Huimeng Wang 3, Zhenjun Chen 3, Jamie Rossjohn 4 5 6, James McCluskey 3, Ligong Liu 1 2, David P Fairlie 1 2
2017 Mar 8