80434-16-8Relevant articles and documents
NUCLEOSIDES FOR SUPPRESSING OR REDUCING THE DEVELOPMENT OF RESISTANCE IN CYTOSTATIC THERAPY
-
Page/Page column 20, (2010/09/17)
The invention relates to special nucleosides, for example, a nucleoside of the formula I, wherein R1-R5 are as described herein, and also to drugs which contain these nucleosides. Furthermore, the invention relates to the use of such nucleosides in a method for suppressing or reducing the formation of resistance in the case of cytostatic treatment of a cancer patient.
Selection of solid dosage form composition through drug-excipient compatibility testing
Serajuddin, Abu T. M.,Thakur, Ajit B.,Ghoshal, Rabin N.,Fakes, Michael G.,Ranadive, Sunanda A.,Morris, Kenneth R.,Varia, Sailesh A.
, p. 696 - 704 (2007/10/03)
A drug-excipient compatibility screening model was developed by which potential stability problems due to interactions of drug substances with excipients in solid dosage forms can be predicted. The model involved storing drug-excipient blends with 20% added water in closed glass vials at 50 °C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drug-excipient blend in a vial was usually kept at about 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Potential roles of several key factors, such as the chemical nature of the excipient, drug-to-excipient ratio, moisture, microenvironmental pH of the drug- excipient mixture, temperature, and light, on dosage form stability could be identified by using the model. Certain physical changes, such as polymorphic conversion or change from crystalline to amorphous form, that could occur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development program would lead to reduction of 'surprise' problems during long-term stability testing of drug products.
Synthesis of Several Pyrimidine L-Nucleoside Analogues as Potential Antiviral Agents
Lin, Tai-Shun,Luo, Mei-Zhen,Liu, Mao-Chin
, p. 1055 - 1068 (2007/10/02)
β-L-5-Iodo-2'-deoxyuridine (β-L-IUdR, 7) and 1-uracil (β-L-BV-ara-U, 10) have been synthesized via a multi-step synthesis from L-arabinose. 2',3'-Dideoxy-β-L-5-azacytidine (18), 2',3'-dideoxy-β-L-2-thiocytidine (20) and their respective α-anomers, compounds 19 and 21, also were synthesized by direct coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (13) with the corresponding silylated bases, in the presence of EtAlCl2 in CH2Cl2, followed by separation of the α- and β-isomers and deblocking of the 5'-protecting groups.In addition, 2',3'-dideoxy-β-L-5-fluorocytidine (34), a potent anti-HIV and anti-HBV agent, was synthesized by an alternative methodology from 2',3'-dideoxy-β-L-5-fluorouridine (31) via a 4-triazolylpyrimidinone intermediate.These L-nucleoside analogues were tested in vitro against HIV, HBV, HSV-1, and HSV-2.Among these compounds, 2',3'-dideoxy-β-L-5-azacytidine (18) was found to show significant activity against HBV in vitro at approximately the same level as 2',3'-dideoxy-β-D-cytidine (ddC), which is a known potent anti-HBV agent.
