49845-33-2Relevant articles and documents
Solid-phase synthesis of N-9-substituted 2,8-diaminopurines
Cole, Andrew G.,Metzger, Axel,Ahmed, Gulzar,Brescia, Marc-Raleigh,Chan, Ray J.,Wen, James,O'Brien, Linda,Qin, Lan-Ying,Henderson, Ian
, p. 8897 - 8900 (2006)
A general and efficient solid-phase synthesis of N-9-substituted 2,8-diaminopurines from 5-nitrouracil is described. The key synthetic transformation employs a carbodiimide-mediated cyclization of a thiourea. Thiourea formation on solid phase is performed
Design, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds
Istanbullu, Huseyin,Bayraktar, Gulsah,Akbaba, Hasan,Cavus, Ibrahim,Coban, Gunes,Debelec Butuner, Bilge,Kilimcioglu, Ali Ahmet,Ozbilgin, Ahmet,Alptuzun, Vildan,Erciyas, Ercin
, (2020)
A series of thiazolopyrimidine derivatives was designed and synthesized as a Leishmania major pteridine reductase 1 (LmPTR1) enzyme inhibitor. Their LmPTR1 inhibitor activities were evaluated using the enzyme produced by Escherichia coli in a recombinant way. The antileishmanial activity of the selected compounds was tested in vitro against Leishmania sp. Additionally, the compounds were evaluated for cytotoxic activity against the murine macrophage cell line RAW 264.7. According to the results, four compounds displayed not only a potent in vitro antileishmanial activity against promastigote forms but also low cytotoxicity. Among them, compound L16 exhibited an antileishmanial activity for both the promastigote and amastigote forms of L. tropica, with IC50 values of 7.5 and 2.69 μM, respectively. In addition, molecular docking studies and molecular dynamics simulations were also carried out in this study. In light of these findings, the compounds provide a new potential scaffold for antileishmanial drug discovery.
Method for preparing 2, 4 - dichloro -5 - nitropyrimidine
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Paragraph 0017; 0020-0032, (2021/09/08)
The invention discloses a method for preparing 2, 4 - dichloro -5 - nitropyrimidine, wherein, 5 - nitro uracil is put into a reactor, and the reaction is stopped when the product content 50 °C 95% or more is increased to 100 °C dropwise DMF. The dichloroethane layer was removed by filtration, and the 2 mixture 4 -dichloro -5 -nitropyrimidine was distilled off under reduced pressure. The reaction conditions are easy to control, operation is simple, yield is high, production cost is low, safety and environmental protection are achieved, and industrial production can be realized.
Efficient Phosphorus-Free Chlorination of Hydroxy Aza-Arenes and Their Application in One-Pot Pharmaceutical Synthesis
Wang, Jian,Li, Yan-Hui,Pan, Song-Cheng,Li, Ming-Fang,Du, Wenting,Yin, Hong,Li, Jing-Hua
supporting information, p. 146 - 153 (2020/03/10)
The chlorination of hydroxy aza-arenes with bis(trichloromethyl) carbonate (BTC) and SOCl2 has been effectively performed by refluxing with 5 wt % 4-dimethylaminopyridine (DMAP) as a catalyst. Various substrates are chlorinated with high yields. The obtained chlorinated aza-arenes can be used directly with simple workup for succedent one-pot synthesis on a large scale.
Preparation method of 2, 4-dichloro-5-nitropyrimidine
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Paragraph 0012-0020, (2019/02/13)
The invention provides a preparation method of 2, 4-dichloro-5-nitropyrimidine. The preparation method comprises: adding 5-nitropyrimidine into a reactor along with stirring, adding phosphorus oxychloride into the reactor, heating the mixture to 50-100 DEG C, adding DMF into the mixture drop by drop so that the mixture undergoes a reaction until the product content of the reaction solution is 95%or more, carrying out reduced pressure recovery on phosphorus oxychloride, feeding dichloroethane into the reaction solution, carrying out mixing, adding the reaction solution into ice water, carryingout hydrolysis and layering, taking out a dichloroethane layer, and carrying out reduced pressure distillation to obtain a 2, 4-dichloro-5-nitropyrimidine finished product. The preparation method hasthe advantages of easy control of reaction conditions, simple operation, high yield, low production cost, safety and environmental friendliness and realizes industrial production.
Preparation method of chloro-substituted polyhydroxy aza-aromatic ring compound (by machine translation)
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Paragraph 0019; 0020; 0021-0024, (2019/10/01)
The invention discloses a preparation method, namely BTC and SOCl, of a chloropolyhydroxyl aza heteroaromatic ring compound as a raw material with a polyhydroxy aza heteroaromatic ring compound as a raw material, and a preparation method thereof. 2 As the double chlorination reagent, a chloropolyhydroxyl aza-aromatic ring compound is produced by chlorination reaction with 4 - dimethylaminopyridine (DMAP) as a catalyst at room temperature to reflux temperature of the reaction, as a catalyst. BTC TC TC TC2 /DMDMAP chlorination system has high efficiency, high selectivity and chlorine substitution on a polyhydroxy nitrogen heterocyclic compound; the system can replace POCl3 , The production of phosphorus-containing wastewater is avoided. Using BTC as a chlorination reagent, the reaction by-product was HCl and CO. 2 . From the aspects of industrial wastewater treatment, environmental protection and the like, the advantages thereof are obvious; SOCl is distilled off after the reaction is ended. 2 The quantity is almost no loss, can be used repeatedly, and reduces the process cost. (by machine translation)
Sulfide Analogues of Flupirtine and Retigabine with Nanomolar KV7.2/KV7.3 Channel Opening Activity
Bock, Christian,Surur, Abdrrahman S.,Beirow, Kristin,Kindermann, Markus K.,Schulig, Lukas,Bodtke, Anja,Bednarski, Patrick J.,Link, Andreas
supporting information, p. 952 - 964 (2019/04/10)
The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electrophilic quinones. These elusive, highly reactive metabolites may induce liver injury in the case of flupirtine and blue tissue discoloration after prolonged intake of retigabine. We examined which structural features can be altered to avoid the detrimental oxidation of the aromatic ring and shift oxidation toward the formation of more benign metabolites. Structure–activity relationship studies were performed to evaluate the KV7.2/3 channel opening activity of 45 derivatives. Sulfide analogues were identified that are devoid of the risk of quinone formation, but possess potent KV7.2/3 opening activity. For example, flupirtine analogue 3-(3,5-difluorophenyl)-N-(6-(isobutylthio)-2-(pyrrolidin-1-yl)pyridin-3-yl)propanamide (48) has 100-fold enhanced activity (EC50=1.4 nm), a vastly improved toxicity/activity ratio, and the same efficacy as retigabine in vitro.
Purine compounds, composition and application
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Paragraph 0066; 0071; 0072, (2017/07/04)
The invention belongs to the technical field of medicine and relates to purine compounds, composition and an application of the composition. The compounds represented as a general formula (I) as well as all possible isomers, pharmaceutical salts or hydrates or the composition of the compounds are used for treating diseases caused by BTK (Bruton tyrosine kinase) and particularly used for treating diffuse large B cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia.
Electron-deficient heteroarenium salts: An organocatalytic tool for activation of hydrogen peroxide in oxidations
?turala, Ji?í,Bohá?ová, Soňa,Chudoba, Josef,Metelková, Radka,Cibulka, Radek
, p. 2676 - 2699 (2015/03/18)
A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quantitative conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ red > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.
Optimisation of LRRK2 inhibitors and assessment of functional efficacy in cell-based models of neuroinflammation
Munoz, Lenka,Kavanagh, Madeline E.,Phoa, Athena F.,Heng, Benjamin,Dzamko, Nicolas,Chen, Ew-Jun,Doddareddy, Munikumar Reddy,Guillemin, Gilles J.,Kassiou, Michael
supporting information, p. 29 - 34 (2015/03/30)
LRRK2IN1 is a highly potent inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 = 7.9 nM), an established target for treatment of Parkinson's disease. Two LRRK2IN1 analogues 1 and 2 were synthesised which retained LRRK2 inhibitory activity (1: IC50 = 72 nM; 2: IC50 = 51 nM), were predicted to have improved bioavailability and were efficacious in cell-based models of neuroinflammation. Analogue 1 inhibited IL-6 secretion from LPS-stimulated primary human microglia with EC50 = 4.26 μM. In order to further optimize the molecular properties of LRRK2IN1, a library of truncated analogues was designed based on docking studies. Despite lacking LRRK2 inhibitory activity, these compounds show antineuroinflammatory efficacy at micromolar concentration. The compounds developed were valuable tools in establishing a cell-based assay for assessing anti-neuroinflammatory efficacy of LRRK2 inhibitors. Herein, we present data that IL-1β stimulated U87 glioma cell line is a reliable model for neuroinflammation, as data obtained in this model were consistent with results obtained using primary human microglia and astrocytes.
