591-08-2Relevant articles and documents
Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ
Rutaganira, Florentine U.,Fowler, Melissa L.,McPhail, Jacob A.,Gelman, Michael A.,Nguyen, Khanh,Xiong, Anming,Dornan, Gillian L.,Tavshanjian, Brandon,Glenn, Jeffrey S.,Shokat, Kevan M.,Burke, John E.
, p. 1830 - 1839 (2016/03/22)
Type III phosphatidylinositol 4-kinase (PI4KIIIβ) is an essential enzyme in mediating membrane trafficking and is implicated in a variety of pathogenic processes. It is a key host factor mediating replication of RNA viruses. The design of potent and specific inhibitors of this enzyme will be essential to define its cellular roles and may lead to novel antiviral therapeutics. We previously reported the PI4K inhibitor PIK93, and this compound has defined key functions of PI4KIIIβ. However, this compound showed high cross reactivity with class I and III PI3Ks. Using structure-based drug design, we have designed novel potent and selective (>1000-fold over class I and class III PI3Ks) PI4KIIIβ inhibitors. These compounds showed antiviral activity against hepatitis C virus. The co-crystal structure of PI4KIIIβ bound to one of the most potent compounds reveals the molecular basis of specificity. This work will be vital in the design of novel PI4KIIIβ inhibitors, which may play significant roles as antiviral therapeutics.
Acyl iodides in organic synthesis. Reactions of acetyl iodide with urea, thiourea, and their N,N′-disubstituted derivatives
Voronkov,Vlasova,Grigor'Eva,Belousova,Vlasov
experimental part, p. 486 - 490 (2009/08/17)
Acetyl iodide reacted with urea and its derivatives to give the corresponding N-substituted products. The reactions of acetyl iodide with thiourea, N,N′-dimethylthiourea, imidazolidine-2-thione, and hexahydropyrimidine-2-thione resulted in the formation o
Bismuth chloride mediated synthesis, antimicrobial, and anti-inflammatory activities of new 4-aryl-2-amino thiazoles
Giridhar,Reddy, R. Buchi,Kumar, A. Sunil,Chandra Mouli
scheme or table, p. 2058 - 2072 (2009/07/18)
Synthesis of 4-aryl-2-Amino thiazoles (3a-u), (4a-c), and (5a-c) was achieved from the reaction of 4-butyl phenacyl chlorides (2a-c) with N-substituted thioureas, in the presence of Bismuth Chloride. The antimicrobial and anti-inflammatory activities of the final products were also studied. Copyright Taylor & Francis Group, LLC.
REACTIONS OF 1,3-DIACYLTHIOUREAS WITH METHOXIDE ION AND WITH AMINES
Kavalek, Jaromir,Jirman, Josef,Sterba, Vojeslav
, p. 120 - 131 (2007/10/02)
Rate constants of base-catalyzed methanolysis and dissociation constants in methanol have been determined for benzylthiourea (II), 1,3-diacetylthiourea (III), 1,3-dibenzoylthiourea (IV), and 1-acetyl-3-benzoylthiourea (V).With the diacyl derivatives III and IV, the reaction of methoxide ion with the neutral substrate is accompanied by that of methoxide with the substrate anion (at higher alkoxide concentrations).Above 0.1 mol l-1 CH3O(-), the rate constants are also affected by medium.The rate of the reaction of neutral diacyl derivative is decreased, and that of the reacti on of methoxide with the substrate anion is rapidly increased.The dissociation constant of II is higher than that of acetylthiourea (I) by about one order of magnitude, but the attack of methoxide on the carbonyl group of II is about three times slower than that in I.The benzoyl group at the N1 nitrogen exhibits a greater activating influence (in both the rate and the equilibrium constants) on the other NHCOR group than the acetyl group does.With V the ratio of methanolysis rate constants is 9:1 in favour of the acetyl group.The reaction of diacetyl derivative III with 1-butanamine has been followed in butanamine buffers.At the lowest butanamine concentrations, the reaction is second order in the amine, and the rate-limiting step is the proton transfer from the intermediate to the second amine molecule.At the highest butanamine concentrations the reaction becomes first order in the amine, and the rate limiting step changes to the attack of butanamine on the carbonyl group of diacetyl derivative III.
Prodrugs as drug delivery systems IV: N-Mannich bases as potential novel prodrugs for amides, ureides, amines, and other NH-acidic compounds
Bundgaard,Johansen
, p. 44 - 46 (2007/10/02)
The hydrolysis kinetics of a series of N-Mannich bases of carboxamides, thioamides, and other NH-acidic compounds were studied to assess their suitability as prodrugs for various drugs. The pH-rate profiles for the compounds were determined at 37° and were accounted for by assuming the spontaneous decomposition of both free and protonated Mannich bases. The reaction rate for the free base increased sharply with increasing steric effects of the amine component of the N-Mannich bases and also with increasing acidity of the amide component. N-Mannich bases may be potentially useful prodrugs for NH-acidic compounds such as various amides, imides, and ureides and for amines.
