538-32-9Relevant articles and documents
Kinetics and mechanism of the aminolysis of aryl thiocarbamates: Effects of the non-leaving group
Oh, Hyuck Keun,Jin, Young Cheul,Sung, Dae Dong,Lee, Ikchoon
, p. 1240 - 1244 (2005)
The kinetics of the aminolysis of aryl thiocarbamates [ATC: H 2NC(=O)SC6H4Z] with benzylamines (XC 6H4CH2NH2) in acetonitrile at 10.0°C have been studied. The rate order with variation of the non-leaving amino group, RNH, in RNHC(=O)SC6H4Z is NH2 s) effects of the RNH group are insignificant, and the strength of push to expel the leaving group in the tetrahedral transition state is the sole, important effect. The strong push provided by the NH2 group, the negative ρxz (-0.38) value, the size of βz (-0.54), and failure of the reactivity-selectivity principle are all consistent with the concerted mechanism. The kinetic isotope effects involving deuterated amine nucleophiles (XC6H4CH2ND2) are normal (kH/kD ≈ 1.40-1.73) suggesting a hydrogen-bonded cyclic transition state. The Royal Society of Chemistry 2005.
Degradation kinetics and mechanism of an oxadiazole derivative, design of a stable drug product for BMS-708163, a γ-secretase inhibitor drug candidate
Hartley, Ruiling F.,Huang, Yande,Cassidy, Michael,Razler, Thomas M.,Qian, Feng,Hussain, Munir A.
, p. 3124 - 3133 (2012)
The stability of a 1,2,4-oxadiazole derivative, BMS-708163, A, was studied in the cosolvent mixture of acetonitrile-water at various pH values, in the solid state and in the presence of various excipients. The objective of this study was to develop a deep understanding of the stability of compound A based on its degradation kinetics and mechanism to enable design of a robust drug product. A series of isotopically 13C- and 15N-labeled compounds were synthesized and their degradation was studied by liquid chromatography-mass spectrometry and nuclear magnetic resonance to prove the degradation mechanism. Compound A exhibited maximum stability at a pH range of 3-5. In forced degradation studies, higher or lower pH resulted in an increase in degradation rate. At low pH, the N-4 atom on the 1,2,4-oxadiazole ring is protonated, followed by nucleophilic attack on the activated methine carbon to cause ring opening to form aryl nitrile degradation product, compound B. At high pH, the nucleophilic attack occurs on the methine carbon to generate an anion on N-4. Subsequent proton capture from a proton donor, such as ambient water, facilitates ring opening to generate compound B. In the absence of a proton donor, such as in dry acetonitrile, anion on N-4 will go back to compound A. Therefore, compound A is stable in absence of proton donor. This study defines the package condition and microenvironmental pH under which compound A can be formulated into a stable product.
Synthesis of Biuret Derivatives as Potential HIV-1 Protease Inhibitors Using (LDHs-g-HMDI-Citric Acid), as a Green Recyclable Catalyst
Ghiasifar, Zahra,Salehabadi, Hafezeh,Adibpour, Neda,Alipour, Eskandar,Kobarfard, Farzad,Shoushizadeh, Mohammad Reza
, p. 48 - 59 (2020/12/07)
In this study, a novel catalyst based on layered double hydroxides (LDHs) attached by hexamethylene-1,6-diisocyanate (HMDI) and citric acid (LDHs-g-HMDI-Citric acid) is reported and used to increase the yield of biurets synthesis. Biuret derivatives 5a–n were prepared by reaction of several phenyl allophanates (3a–d), which prepared from the reaction of phenyl chloroformate and urea derivatives (2a–d), with variously substituted amines (4a–g) in the presence of LDHs-g-HMDI-Citric acid as a reusable heterogeneous catalyst at reflux condition for 60–180 min. These biurets (5a–n) were evaluated for human immunodeficiency virus type-1 (HIV-1) protease inhibitory activity by HIV-1 p24 antigen ELISA kit and six of them (5n, 5i, 5j, 5 m, 5f, and 5a) showed moderate activity on HIV-1 virus with IC50 values ranging from 55 to 100 μM compared with the azidothymidine as the reference drug (IC50 = 0.11 μM). Results of the in vitro test and docking study were in good correlation.
Green and efficient synthesis of thioureas, ureas, primary: O -thiocarbamates, and carbamates in deep eutectic solvent/catalyst systems using thiourea and urea
Bagherzadeh, Nastaran,Sardarian, Ali Reza,Inaloo, Iman Dindarloo
supporting information, p. 11852 - 11858 (2021/07/12)
An efficient and general catalysis process was developed for the direct preparation of various primary O-thiocarbamates/carbamates as well as monosubstituted thioureas/ureas by using thiourea/urea as biocompatible thiocarbonyl (carbonyl) sources. This procedure used choline chloride/tin(ii) chloride [ChCl][SnCl2]2 with a dual role as a green catalyst and reaction medium to afford the desired products in moderate to excellent yields. Moreover, the DES can be easily recovered and reused for seven cycles with no significant loss in its activity. Besides, the method shows very good performance for synthesizing the desired products on a large scale.